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Infections with Entamoeba histolytica are seen worldwide and are more prevalent in the tropics. About 90% of infections are asymptomatic, and the remaining 10% produce a spectrum of clinical syndromes, ranging from dysentery to abscesses of the liver or other organs. Extra-intestinal infection by E. histolytica most often involves liver. Pleuro-pulmonary involvement, seen as the second most common extra-intestinal pattern of infection, is frequently associated with amebic liver abscess. Pulmonary amebiasis occurs in about 2-3% of patients with invasive amebiasis. We report herein the case of a 45-year-old male presenting with hepato-pulmonary amebiasis. The diagnosis was established from direct examination of sputum, in which trophozoites of E. histolytica were detected, and by serology. Following treatment with metronidazole and chloroquine, the clinical evolution improved significantly. On regular follow-up visits, the patient was asymptomatic. This case report reiterates the need for collaboration between clinicians and microbiologists for timely diagnosis of such infections. Keywords: Entamoeba histolytica, liver abscess, microscopy, pulmonary involvement

Localized surface plasmon resonance (LSPR) gas sensitivity is introduced as a new parameter to evaluate the performance of plasmonic gas sensors. A model is proposed to consider the plasmonic sensors' surface sensitivity and plasmon decay length and correlate the LSPR response, measured upon gas exchange, with an equivalent refractive index change consistent with adsorbed gas layers. To demonstrate the applicability of this new parameter, ellipsoidal gold nanoparticles (NPs) arranged in densely packed hexagonal lattices were fabricated. The main advantages of these sensors are the small and tunable interparticle gaps (18-29 nm) between nanoparticles (diameters: 72-88 nm), with their robust and scalable fabrication technology that allows the well-ordered arrangement to be maintained on a large (cm 2 range) area. The LSPR response of the sensors was tested using an LSPR sensing system by switching the gas atmosphere between inorganic gases, namely He/Ar and Ar/CO 2 , at constant pressure and room temperature. It was shown that this newly proposed parameter can be generally used for benchmarking plasmonic gas sensors and is independent of the type and pressure of the tested gases for a sensor structure. Furthermore, it resolves the apparent disagreement when comparing the response of plasmonic sensors tested in liquids and gases.

Atomic force microscopy (AFM) imaging enables the visualization of protein molecules with high resolution, providing insights into their shape, size, and surface topography. Here, we use AFM to study the aggregation process of protein S100A9 in physiological conditions, in the presence of calcium at a molar ratio 4Ca 2+ :S100A9. We find that S100A9 readily assembles into a worm-like fibril, with a period dimension along the fibril axis of 11.5 nm. The fibril's chain length extends up to 136 periods after an incubation time of 144 h. At room temperature, the fibril's bending stiffness was found to be 2.95×10-28 Nm 2 , indicating that the fibrils are relatively flexible. Additionally, the values obtained for the Young's modulus (Ex=6.96×105 Pa and Ey=3.37×105 Pa) are four orders of magnitude lower than those typically reported for canonical amyloid fibrils. Our findings suggest that, under the investigated conditions, a distinct aggregation mechanism may be in place in the presence of calcium. Therefore, the findings reported here could have implications for the field of biomedicine, particularly with regard to Alzheimer's disease.

Major Depressive Disorder (MDD) is a severe and multifactorial psychiatric condition. Evidence has shown that environmental factors, such as stress, significantly explain MDD pathophysiology. Studies have hypothesized that changes in histone methylation patterns are involved in impaired glutamatergic signaling. Based on this scenario, this study aims to investigate histone 3 involvement in depression susceptibility or resilience in MDD pathophysiology by investigating cellular and molecular parameters related to i) glutamatergic neurotransmission, ii) astrocytic functioning, and iii) neurogenesis. For this, we subjected male Wistar rats to the Chronic Unpredictable Mild Stress (CUMS) model of depression. We propose that by evaluating the sucrose consumption, open field, and object recognition test performance from animals submitted to CUMS, it is possible to predict with high specificity rats with susceptibility to depressive-like phenotype and resilient to the depressive-like phenotype. We also demonstrated, for the first time, that patterns of H3K4me3, H3K9me3, H3K27me3, and H3K36me3 trimethylation are strictly associated with the resilient or susceptible to depressive-like phenotype in a brain-region-specific manner. Additionally, susceptible animals have reduced DCx and GFAP and resilient animals present increase of AQP-4 immunoreactivity. Together, these results provide evidence that H3 trimethylations are related to the development of the resilient or susceptible to depressive-like phenotype, contributing to further advances in the pathophysiology of MDD and the discovery of mechanisms behind resilience., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Familial hypercholesterolemia (FH) is caused by mutations in the gene that encodes the low-density lipoprotein (LDL) receptor, which leads to an excessive increase in plasma LDL cholesterol levels. Previous studies have shown that FH is associated with gliosis, blood-brain barrier dysfunction, and memory impairment, but the mechanisms associated with these events are still not fully understood. Therefore, we aimed to investigate the role of microgliosis in the neurochemical and behavioral changes associated with FH using LDL receptor knockout (LDLr -/- ) mice. We noticed that microgliosis was more severe in the hippocampus of middle-aged LDLr -/- mice, which was accompanied by microglial morphological changes and alterations in the immunocontent of synaptic protein markers. At three months of age, the LDLr -/- mice already showed increased microgliosis and decreased immunocontent of claudin-5 in the prefrontal cortex (PFC). Subsequently, 6-month-old male C57BL/6 wild-type and LDLr -/- mice were treated once daily for 30 days with minocycline (a pharmacological inhibitor of microglial cell reactivity) or vehicle (saline). Adult LDLr -/- mice displayed significant hippocampal memory impairment, which was ameliorated by minocycline treatment. Non-treated LDLr -/- mice showed increased microglial density in all hippocampal regions analyzed, a process that was not altered by minocycline treatment. Region-specific microglial morphological analysis revealed different effects of genotype or minocycline treatment on microglial morphology, depending on the hippocampal subregion analyzed. Moreover, 6-month-old LDLr -/- mice exhibited a slight but not significant increase in IBA-1 immunoreactivity in the PFC, which was reduced by minocycline treatment without altering microglial morphology. Minocycline treatment also reduced the presence of microglia within the perivascular area in both the PFC and hippocampus of LDLr -/- mice. However, no significant effects of either genotype or minocycline treatment were observed regarding the phagocytic activity of microglia in the PFC and hippocampus. Our results demonstrate that hippocampal microgliosis, microglial morphological changes, and the presence of these glial cells in the perivascular area, but not increased microglial phagocytic activity, are associated with cognitive deficits in a mouse model of FH., (© 2023 International Society for Neurochemistry.)

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Extreme weather events driven by climate change threaten the resilience of urban structures and urban dwellers. Nature-based Solutions (NbS) are an effective tool to reduce urban vulnerability to climate risks and, at the same time, develop more liveable urban areas. Despite the acknowledged positive impacts of individual observed NbS, numerous questions persist unanswered. While existing research supports NbS' positive influence on urban climate adaptation, the extent of their impact remains insufficiently studied. Understanding the magnitude of NbS impact is crucial for justifying their preference over non-NbS alternatives and, consequently, for securing public investment. Via a meta-analysis, this paper aims to contribute to research and practice by providing a more systematic assessment of NbS effects, offering urban planners and decision-makers a robust justification for their incorporation in climate change adaptation, urban resilience, and enhanced liveability. The results of the meta-analytic model indicate that the effect of NbS is indeed positive. When assessing the impact on temperature and flood protection, there is a general positive effect across the studied NbS. However, when evaluating an average effect, the task appears to be more complex due to methodological issues and limitations. The need to increase the formalisation of how the impact of NbS is measured and reported also emerges as a result. Replicable protocols would positively impact the formalisation of the literature on the topic and positively affect the evidence-based support for the implementation of NbS by urban decision-makers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Splenic artery aneurysms (SAAs) are rare but seem to have higher incidence in patients with portal hypertension (PH). The present article aims to analyze the interference of PH in the natural history of these aneurysms., Methods: This was a retrospective study of data recorded prospectively. Between January 2000 and December 2019, all SAAs patients in follow-up at a tertiary institution were selected for analysis. Primary end point was to analyze the presentation and evolution of SAAs in patients with PH, and secondary was to identify cumulative rates of freedom from rupture, interventions, and survival in this group, during a 10-year follow-up., Results: In total, 96 patients were identified with SAAs, 79 (82.29%) did not have PH and 17 (17.7%) had this comorbidity. Among the demographic characteristics, the patients with SAAs and PH were significantly younger (52 years [standard deviation {SD} 13.3] versus 61.9 years [SD 12.2] [P = 0.05]) and had lower number of pregnancies (1.1 pregnancies [SD 1.2] versus 3.37 pregnancies [SD 2.3] [P = 0.03]). Patients with PH had a higher cumulative rate of surgical intervention throughout follow-up (up to 75.6% in 10 years) when compared to patients without PH, with 36.9% intervention rate in 10 years of follow-up. Patients with PH had larger diameter at diagnosis (35 mm, SD 27.3) compared to patients without PH (22.6 mm, SD 16.1), P = 0.008. However, there were no statistical differences in the relative growth rate, in aneurysmal rupture rate throughout follow-up, as well as in survival over the years, between the groups., Conclusions: The patients with SAAs and PH are significantly younger, have larger SAA diameters at diagnosis and have a higher cumulative rate of surgical intervention throughout follow-up in 10 years, despite the relative growth rate being similar to that of patients without PH., (Copyright © 2024 Elsevier Inc. All rights reserved.)

STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20 min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy., (© 2023. The Author(s).)

Research Background: Açaí berry is rich in antioxidant compounds and is therefore closely associated with beneficial health effects. In this study, we aim to investigate the potential of using Lacticaseibacillus rhamnosus HN001 as a probiotic culture on açaí flan., Experimental Approach: The chemical composition, physicochemical and microbiological characteristics, and sensory acceptance during refrigerated storage (5 °C for 42 days) of flan were investigated. In addition, the consumer perception of the product was evaluated using word association when consumers were shown a photo of the product with or without the added ingredients accompanied with a brief description of the product., Results and Conclusions: The flan had a suitable chemical composition, mainly carbohydrates and proteins, probiotic viability reached 8 log CFU/g in the product and 4 log CFU/g after gastrointestinal simulation, typical açaí coloration, significant antioxidant activity and high sensory acceptability. The information about the ingredients and properties of the products increased the health value and positive feelings of the consumers towards the product., Novelty and Scientific Contribution: Açaí flan has proven to be a suitable carrier for L. rhamnosus HN001 as a probiotic culture, further enhancing the characteristic beneficial properties of the fruit. Therefore, combining this information with marketing strategies that inform consumers about the benefits of the product can further improve its acceptance. As far as we know, this is the first study on açaí flan with added probiotic culture., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest., (Authors.)

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The present study aimed was to evaluate the spatial variability of weed species by means of phytosociological parameters and their correlations with the physical-chemical soil properties, under semiarid climate conditions. Weed phytosociology and soil characterization were carried out in two areas one newly deforested area covering 8.86 ha, and one experimental agricultural area covering 24.7 ha; both in the semi-arid region of Brazil. Weed and soil were sampled by following georeferenced grids in each area. Biomass and the total number of weed individuals, as well as soil properties, were mapped by the ordinary Kriging method. The predominant herbaceous plants in the newly deforested area were Hexasepalum teres and Digitaria insularis. The weed species that predominated in the agricultural area were Cyperus rotundus L., Euphorbia heterophylla L. and Herissantia Crispa (L.) Brizicky; the latter species outstanding for dry biomass (873.5g). Spatial dependence was observed for the predominant species, except for Digitaria insularis. The spatial distribution of these weeds was conditioned by soil K+ contents in both areas, and by sand content for the experimental agricultural area. Therefore, these two soil attributes resulted key factors for weed infestation in this semi-arid region.

The extinction efficiency of noble metal nanoparticles (NPs), namely gold (Au) and silver (Ag), are dependent on their size and surrounding dielectric. Exploiting the Localized Surface Plasmon Resonance (LSPR) phenomenon, the composition and structure of the NPs might be tailored to achieve a configuration that optimizes their response (sensitivity) to environmental changes. This can be done by preparing a bimetallic system, benefiting from the chemical stability of Au NPs and the higher scattering efficiency of Ag NPs. To enhance the LSPR sensing robustness, incorporating solid supports in the form of nanocomposite thin films is a suitable alternative. In this context, the NPs composed of gold (Au), silver (Ag), and their mixture in bimetallic Au-Ag NPs, were grown in a titanium dioxide (TiO 2 ) matrix using reactive DC magnetron sputtering. Thermal treatment at different temperatures (up to 700 °C) tuned the LSPR response of the films and, consequently, their sensitivity. Notably, the bimetallic film with Au/Ag atomic ratio 1 exhibited the highest refractive index sensitivity (RIS), with a value of 181 nm/RIU, almost one order of magnitude higher than monometallic Au-TiO 2 . The nanostructural analysis revealed a wide NP size distribution of bimetallic NPs with an average size of 31 nm, covering about 20% of the overall surface area. These findings underscore the significant potential of bimetallic film systems, namely AuAg-TiO 2 , in LSPR sensing enhancement.

This work reports on the development of nanoplasmonic thin films consisting of Au, Ag, or Au-Ag nanoparticles dispersed in a TiO 2 matrix and the optimization of the deposition parameters to tune their optical response. The thin films were produced by reactive DC magnetron sputtering of a Ti target with Au and/or Ag pellets placed on the erosion zone. The thicknesses (50 and 100 nm) of the films, the current density (75 and 100 A/m 2 ) applied to the target (titanium), and the number of pellets placed on its surface were the deposition conditions that were used to tailor the optical (LSPR) response. The total noble metal content varied between 13 and 28 at.% for Au/TiO 2 films, between 22 and 30 at.% for Ag/TiO 2 films, and 8 to 29 at% for the Au-Ag/TiO 2 systems with 1:1, 1:1.5, and 1:2 Au:Ag atomic ratios. After thermal annealing at 400 and 600 °C, LSPR bands were found for all films concerning the Au-TiO 2 and Au-Ag/TiO 2 , while for Ag/TiO 2 , only for thin films with 28 and 30 at.% of Ag concentration. Refractive index sensitivity (RIS) was evaluated for Au and Au-Ag/TiO 2 thin films. It was found that for bimetallic nanoparticles, the sensitivity can increase up to five times when compared to a monometallic nanoplasmonic system. Using Au-Ag/TiO2 thin films can decrease the cost of fabrication of LSPR transducers while improving their sensitivity.

Inflammatory bowel diseases (IBD) cause increased inflammatory signalling and oxidative damage. IBDs are correlated with an increased incidence of brain-related disorders suggesting that the gut-brain-axis exerts a pivotal role in IBD. Butyrate is one of the main microbial metabolites in the colon, and it can cross the blood-brain barrier, directly affecting the brain. We induced ulcerative colitis (UC) in mice utilizing dextran sodium sulfate (DSS) in the drinking water for 7 days. Animals were divided into four groups, receiving water or DSS and treated with saline or 0,066 g/kg of Sodium Butyrate for 7 days. We also used an integrative approach, combining bioinformatics functional network and experimental strategies to understand how butyrate may affect UC. Butyrate was able to attenuate colitis severity and intestinal inflammation. Butyrate protected the colon against oxidative damage in UC and protected the prefrontal cortex from neuroinflammation observed in DSS group. Immunocontent of tight junction proteins Claudin-5 and Occludin were reduced in colon of DSS group mice and butyrate was able to restore to control levels. Occludin and Claudin-5 decrease in DSS group indicate that an intestinal barrier disruption may lead to the increased influx of gut-derived molecules, causing neuroinflammation in the prefrontal cortex, observed by increased IBA-1 marker. The probable protection mechanism of butyrate treatment occurs through NRF2 through Nrf2 and HIF-1α activation and consequent activation of catalase and superoxide dismutase. Our data suggest that systemic inflammation associated with intestinal barrier disruption in UC leads to neuroinflammation in the prefrontal cortex, which was atenuated by butyrate.

The aims of this work were to evaluate the reactivity of sugarcane straw ashes (SCSA) burned under controlled conditions and to analyze their reactivity in blended cement and hydrated lime pastes by thermogravimetric analysis (TG) and calorimetry. Four different ashes were produced, and burned at 600 °C, 700 °C, 800 °C and 900 °C (SCSA600, SCSA700, SCSA800 and SCSA900, respectively). These ashes were characterized by X-ray fluorescence spectroscopy, X-ray diffractometry, particle size distribution by laser diffraction and specific area surfaces to assess their potential interest in the partial replacement of inorganic binders (Portland cement (OPC) and hydrated lime). The hydrated lime pastes were subjected to scanning electron microscopy (SEM) and TG. The blended cement pastes were analyzed by TG and calorimetry, compressive strength testing and mercury intrusion porosimetry. High lime fixation percentages were observed in the hydrated lime and OPC pastes and were higher than 75% and 50% for the ashes burned at 600 °C and 700 °C, respectively. Calorimetry showed a delay in the heat release of SCSA600 and SCSA700 compared to the control paste. These pastes also had higher compressive strength and a smaller total pore volume. The results indicate the positive response of preparing sugar cane ashes under controlled conditions (mainly for straw calcined within the 600-700 °C range) for their use as pozzolanic addition by partially replacing inorganic binders.

Environmental changes alter the sex fate in about 15% of vertebrate orders, mainly in ectotherms such as fish and reptiles. However, the effects of temperature changes on the endocrine and molecular processes controlling gonadal sex determination are not fully understood. Here, we provide evidence that thyroid hormones (THs) act as co-players in heat-induced masculinization through interactions with the stress axis to promote testicular development. We first demonstrated that the thyroid axis (through thyroid-related genes and T3 levels) is highly active in males during the gonadal development in medaka (Oryzias latipes). Similarly, T3 treatments promoted female-to-male sex reversal in XX embryos. Subsequently, embryonic exposure to temperature-induced stress up-regulated the genes related to the thyroid and stress axes with a final increase in T3 levels. In this context, we show that blocking the stress axis response by the loss of function of the corticotropin-releasing hormone receptors suppresses thyroid-stimulating hormone expression, therefore, heat-induced activation of the thyroid axis. Thus, our data showed that early activation of the stress axis and, in consequence, the TH axis, too, leaves us with that both being important endocrine players in inducing female-to-male reversal, which can help predict possible upcoming physiological impacts of global warming on fish populations., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

An efficient method of genomic DNA extraction that provides high quality and yield is a crucial pre-requisite and limiting factor in plant genetic analysis. However, pure genomic DNA can be challenging to obtain from some plant species due to their sugar and secondary metabolite contents. Lippia alba is an important aromatic and medicinal plant, chemically characterized by the presence of tannins, flavonoids, anthocyanins, and essential oils, which interfere with the extraction of pure genomic DNA. In this scenario, optimizing the extraction methods and minimizing the effects of these compounds are necessary. This study compares six plant DNA extraction protocols based on the CTAB method. The quality and quantity of DNA samples obtained were determined by physical appearance by electrophoresis in agarose gels and spectrophotometry. The results highlight the difficulty in obtaining pure and clear bands for all tested methods, except for the polyvinylpyrrolidone (PVP)-based protocol created by our team, which was the better option for obtaining high-quality genomic DNA of L. alba. We conclude that adding PVP-40 into DNA extraction buffers can optimize the DNA extraction of L. alba and indicate this protocol for DNA extraction from other aromatic plants., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Stroke is a major cause of mortality worldwide. Renal dysfunction is an important risk factor for stroke. Brazilian studies on stroke knowledge are generally population based. Studies stratifying stroke knowledge according to comorbidities are rare. Scientific data are essential to guide the awareness of stroke., Objective: To assess stroke knowledge in patients with chronic kidney disease (CKD) on hemodialysis., Design and Setting: Cross-sectional analytical study of patients with CKD on hemodialysis in north-eastern Brazil., Methods: A self-administered questionnaire survey on stroke awareness was administered to patients with CKD on hemodialysis between April and November 2022. The chi-square test and other descriptive statistics were used. Univariate and multivariate analyses were performed using logistic regression., Results: A total of 197 patients were included in the analysis. The Brazilian acronym for stroke was used by 53.5% of the participants. Less than 10.0% of the sample showed optimal decision-making ability regarding stroke. Of the participants, 29.9% knew at least one risk factor and one symptom; however, this was considered as having below the minimum capacity because they did not know the emergency service call number. In the analysis adjusted for income and education, females (odds ratio [OR], 0.40%; 95% confidence interval [CI], 0.20-0.82), older patients (OR, 0.24%; 95% CI, 0.09-0.63) and having at most one comorbidity (OR, 0.48%; 95% CI, 0.23-0.98) were factors for lower levels of knowledge or ideal decision-making capacity against stroke., Conclusions: Patients on hemodialysis, especially women and older people, have little knowledge about stroke.

Gutta-percha's lack of adhesion has been presented as a drawback to avoid gaps at sealer/gutta-percha interface. Plasma treatments have been scarcely assessed on gutta-percha surfaces as a method of enhancing adhesiveness. This study aimed to evaluate the effect of low-pressure Argon and Oxygen plasma atmospheres on conventional and bioceramic gutta-percha standardized smooth discs, assessing their roughness, surface free energy, chemical structure, and sealer wettability. A Low-Pressure Plasma Cleaner by Diener Electronic (Zepto Model) was used. Different gases (Argon or Oxygen), powers (25 W, or 50 W), and exposure times (30 s, 60 s, 120 s, or 180 s) were tested in control and experimental groups. Kruskal-Wallis and Student's t-test were used in data analysis. Statistically significant differences were detected when P < 0.05. Both gases showed different behaviors according to the parameters selected. Even though chemical changes were detected, the basic molecular structure was maintained. Argon or Oxygen plasma treatments favoured the wetting of conventional and bioceramic gutta-perchas by Endoresin and AH Plus Bioceramic sealers (P < 0.001). Overall, the functionalization of gutta-percha surfaces with Argon or Oxygen plasma treatments can increase roughness, surface free energy and wettability, which might improve its adhesive properties when compared to non-treated gutta-percha., (© 2023. The Author(s).)

Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.

Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.

Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive organism. This protein was shown to be a FMN containing menaquinone reducing enzyme, presenting a Michaelis-Menten behaviour towards the two substrates, which was inhibited by Brequinar, Leflunomide, Lapachol, HQNO, Atovaquone and TFFA with different degrees of effectiveness. Deletion of the DHOQO coding gene (Δdhoqo) led to lower bacterial growth rates, and effected in cell morphology and metabolism, most importantly in the pyrimidine biosynthesis, here systematized for S. aureus MW2 for the first time. This work unveils the existence of a functional DHOQO in the respiratory chain of the pathogenic bacterium S. aureus, enlarging the understanding of its energy metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Women older than 60 have a higher risk of dementia, aging-related cognitive decline, and Alzheimer's Disease (AD) than the rest of the population. The main reason is hormonal senescence after menopause, a period characterized by a decline in estrogen levels. Since the effectiveness of drugs currently approved for the treatment of AD is limited, it is necessary to seek the development of new therapeutic strategies. Vitamin D deficiency is prevalent in AD patients and individuals with dementia in general. The supplementation of this vitamin in dementia patients might be an interesting approach for increasing the effectiveness of pre-existing medications for dementia treatment. Thus, the present study aims to investigate the effect of vitamin D treatment associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for five months and subjected to a dementia animal model induced by intracerebroventricular injection of aggregated amyloid βeta (Aβ 1 - 42 ). For this purpose, Balb/c mice were divided into five experimental groups, which received 17 days of combined therapy with vitamin D, donepezil, and memantine. Then, animals were subjected to behavioral tests. OVX groups exhibited reduced levels of estradiol (E2) in serum, which was not altered by the combined therapy. Higher levels of vitamin D3 were found in the OVX animals submitted to the triple-association treatment. Mice exposed to both OVX and the dementia animal model presented impairment in short and long-term spatial and habituation memories. Also, female mice exposed to Aβ and OVX exhibited a reduction in brain-derived neurotrophic factor (BDNF) and interleukin-4 (IL-4) levels, and an increase in tumor necrose factor-α (TNFα) levels in the hippocampus. Besides, increased levels of IL-1β in the hippocampus and cerebral cortex were observed, as well as a significant increase in immunoreactivity for glial fibrillary acidic protein (GFAP), an astrocytes marker, in the hippocampus. Notably, triple-association treatment reversed the effects of the exposition of mice to Aβ and OVX in the long-term spatial and habituation memories impairment, as well as reversed changes in TNFα, IL-1β, IL-4, and GFAP immunoreactivity levels in the hippocampus of treated animals. Our results indicate that the therapeutic association of vitamin D, memantine, and donepezil has beneficial effects on memory performance and attenuated the neuroinflammatory response in female mice subjected to OVX associated with a dementia animal model., Competing Interests: Conflict of interest We declare that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Adenosine receptors mainly control synaptic function, and excessive activation of adenosine receptors may worsen the onset of many neurological disorders. Accordingly, the regular intake of moderate doses of caffeine antagonizes adenosine receptors and affords robust neuroprotection. Although caffeine intake alters brain functional connectivity and multi-omics analyses indicate that caffeine intake modifies synaptic and metabolic processes, it is unclear how caffeine intake affects behavior, synaptic plasticity and its modulation by adenosine. We now report that male mice drinking caffeinated water (0.3 g/L) for 2 weeks were behaviorally indistinguishable (locomotion, mood, memory) from control mice (drinking water) and displayed superimposable synaptic plasticity (long-term potentiation) in different brain areas (hippocampus, prefrontal cortex, amygdala). Moreover, there was a general preservation of the efficiency of adenosine A 1 and A 2A receptors to control synaptic transmission and plasticity, although there was a tendency for lower levels of endogenous adenosine ensuring A 1 receptor-mediated inhibition. In spite of similar behavioral and neurophysiological function, caffeine intake increased the energy charge and redox state of cortical synaptosomes. This increased metabolic competence likely involved a putative increase in the glycolytic rate in synapses and a prospective greater astrocyte-synapse lactate shuttling. It was concluded that caffeine intake does not trigger evident alterations of behavior or of synaptic plasticity but increases the metabolic competence of synapses, which might be related with the previously described better ability of animals consuming caffeine to cope with deleterious stimuli triggering brain dysfunction.

Nanotechnology is an emerging and expanding technology worldwide. The manipulation of materials on a nanometric scale generates new products with unique properties called nanomaterials. Due to its significant expansion, nanotechnology has been applied in several fields of study, including developing materials for biomedical applications, i.e., nanomedicine. The use of nanomaterials, including nanoparticles, in nanomedicine, is promising and has been associated with pharmacokinetics, bioavailability, and therapeutic advantages. In this regard, it is worth mentioning the Gold Nanoparticles (AuNPs). AuNPs' biomedical application is extensively investigated due to their high biocompatibility, simple preparation, catalytic, and redox properties. Experimental studies have pointed out critical therapeutic actions related to AuNPs in different pathophysiological contexts, mainly due to their anti-inflammatory and antioxidant effects. Thus, in this review, we will discuss the main experimental findings related to the therapeutic properties of AuNPs in metabolic, neurodegenerative diseases, and ultimately brain dysfunctions related to metabolic diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cholesterol is a lipid molecule of great biological importance to animal cells. Dysregulation of cholesterol metabolism leads to raised blood total cholesterol levels, a clinical condition called hypercholesterolemia. Evidence has shown that hypercholesterolemia is associated with the development of liver and heart disease. One of the mechanisms underlying heart and liver alterations induced by hypercholesterolemia is oxidative stress. In this regard, in several experimental studies, gold nanoparticles (AuNP) displayed antioxidant properties. We hypothesized that hypercholesterolemia causes redox system imbalance in the liver and cardiac tissues, and AuNP treatment could ameliorate it. Young adult male Swiss mice fed a regular rodent diet or a high cholesterol diet for eight weeks and concomitantly treated with AuNP (2.5 μg/kg) or vehicle by oral gavage. Hypercholesterolemia increased the nitrite concentration and glutathione (GSH) levels and decreased the liver's superoxide dismutase (SOD) activity. Also, hypercholesterolemia significantly enhanced the reactive oxygen species (ROS) and GSH levels in cardiac tissue. Notably, AuNP promoted the redox system homeostasis, increasing the SOD activity in hepatic tissue and reducing ROS levels in cardiac tissue. Overall, our data showed that hypercholesterolemia triggered oxidative stress in mice's liver and heart, which was partially prevented by AuNP treatment.

Objectives: To classify the most up-to-date factors associated with COVID-19 disease outcomes in Brazil., Design: Retrospective study., Setting: Nationwide Brazilian COVID-19 healthcare registers., Participants: We used healthcare data of individuals diagnosed with mild/moderate (n=70 056 602) or severe (n=2801 380) COVID-19 disease in Brazil between 26 February 2020 and 15 November 2021., Main Outcome Measures: Risk of hospitalisation and mortality affected by demographic, clinical and socioeconomic variables were estimated. The impacts of socioeconomic inequalities on vaccination rates, cases and deaths were also evaluated., Results: 15.6 million SARS-CoV-2 infection cases and 584 761 COVID-19-related deaths occurred in Brazil between 26 February 2020 and 15 November 2021. Overall, men presented a higher odds of death than women (OR=1.14, 95% CI 1.13 to 1.15), but postpartum patients admitted to hospital wards were at increased odds of dying (OR=1.23, 95% CI 1.13 to 1.34) compared with individuals without reported comorbidities. Death in younger age groups was notably higher in most deprived municipalities and also among individuals <40 years belonging to indigenous backgrounds compared with white patients, as shown by descriptive analysis. Ethnic/racial backgrounds exhibited a continuum of decreasing survival chances of mixed-race (OR=1.11, 95% CI 1.10 to 1.12), black (OR=1.34, 95% CI 1.32 to 1.36) and indigenous (OR=1.42, 95% CI 1.31 to 1.54) individuals, while those in most deprived municipalities also presented an increased odds of death (OR=1.38, 95% CI 1.36 to 1.40). Deprivation levels also affect the prompt referral of patients to adequate care. Our results show that the odds of death of individuals hospitalised for less than 4 days is more than double that of patients with close-to-average hospital stays (OR=2.07, 95% CI 2.05 to 2.10). Finally, negative vaccination status also increased the odds of dying from the disease (OR=1.29, 95% CI 1.28 to 1.31)., Conclusions: The data provide evidence that the patterns of COVID-19 mortality in Brazil are influenced by both individual-level health and social risk factors, as well as municipality-level deprivation. In addition, these data suggest that there may be inequalities in the timely provision of appropriate healthcare that are related to municipality-level deprivation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Currently, there is an increasing need to develop highly sensitive plasmonic sensors able to provide good biocompatibility, flexibility, and optical stability to detect low levels of analytes in biological media. In this study, gold nanoparticles (Au NPs) were dispersed into chitosan membranes by spin coating. It has been demonstrated that these membranes are particularly stable and can be successfully employed as versatile plasmonic platforms for molecular sensing. The optical response of the chitosan/Au NPs interfaces and their capability to sense the medium's refractive index (RI) changes, either in a liquid or gas media, were investigated by high-resolution localized surface plasmon resonance (HR-LSPR) spectroscopy, as a proof of concept for biosensing applications. The results revealed that the lowest polymer concentration (chitosan (0.5%)/Au-NPs membrane) presented the most suitable plasmonic response. An LSPR band redshift was observed as the RI of the surrounding media was incremented, resulting in a sensitivity value of 28 ± 1 nm/RIU. Furthermore, the plasmonic membrane showed an outstanding performance when tested in gaseous atmospheres, being capable of distinguishing inert gases with only a 10 -5 RI unit difference. The potential of chitosan/Au-NPs membranes was confirmed for application in LSPR-based sensing applications, despite the fact that further materials optimization should be performed to enhance sensitivity.

In this study, thin films composed of gold nanoparticles embedded in a copper oxide matrix (Au:CuO), manifesting Localized Surface Plasmon Resonance (LSPR) behavior, were produced by reactive DC magnetron sputtering and post-deposition in-air annealing. The effect of low-power Ar plasma etching on the surface properties of the plasmonic thin films was studied, envisaging its optimization as gas sensors. Thus, this work pretends to attain the maximum sensing response of the thin film system and to demonstrate its potential as a gas sensor. The results show that as Ar plasma treatment time increases, the host CuO matrix is etched while Au nanoparticles are uncovered, which leads to an enhancement of the sensitivity until a certain limit. Above such a time limit for plasma treatment, the CuO bonds are broken, and oxygen is removed from the film's surface, resulting in a decrease in the gas sensing capabilities. Hence, the importance of the host matrix for the design of the LSPR sensor is also demonstrated. CuO not only provides stability and protection to the Au NPs but also promotes interactions between the thin film's surface and the tested gases, thereby improving the nanocomposite film's sensitivity. The optimized sensor sensitivity was estimated at 849 nm/RIU, which demonstrates that the Au-CuO thin films have the potential to be used as an LSPR platform for gas sensors.

Background: Stroke is one of the main causes of death worldwide. Educational interventions on stroke are potentially effective in reducing the period between the onset of symptoms and the initial emergency medical assistance., Objectives: To assess high school students' knowledge of stroke., Design and Setting: Cross-sectional study conducted in high schools in northeastern Brazil., Methods: A self-structured questionnaire survey regarding stroke awareness was applied among high school students in northeastern Brazil. Data were collected between 2018 and 2019. The chi-square test and other descriptive statistics were used. Univariate and multivariate analyses were performed using logistic regression., Results: A total of 1,788 students were analyzed. Eighty percent (n = 1430) of them did not have the minimum knowledge on how to act in a stroke situation. Only 10% (n = 179) presented the ideal knowledge on how to act. Males presented lower levels of knowledge on risk factors (odds ratio, OR: 0.62%; 95% confidence interval, CI: 0.49-0.79) and signs and symptoms of stroke (OR: 0.63%; 95% CI: 0.52-0.77). Students with ≥ 10 years of schooling (OR: 1.64%; 95% CI: 1.30-2.07) demonstrated greater knowledge of signs and symptoms of stroke. Students aged 18 years (OR: 1.70%; 95% CI: 1.14-2.52) demonstrated greater knowledge than other ages regarding the telephone number of the emergency medical services., Conclusions: There was a knowledge deficit with regard to recognizing stroke and activating the emergency medical services. The findings apply to the sample investigated and suggest that there is a need for stroke educational interventions, starting in high school.

Objective: This study aims to describe clinical findings and determine the medium-term survival of congenital zika syndrome (CZS) suspected cases., Methods: A retrospective cohort study using routine register-based linked data. It included all suspected cases of CZS born in Brazil from January 1, 2015, to December 31, 2018, and followed up from birth until death, 36 months, or December 31, 2018, whichever came first. Latent class analysis was used to cluster unconfirmed cases into classes with similar combinations of anthropometry at birth, imaging findings, maternally reported rash, region, and year of birth. Kaplan-Meier curves were plotted, and Cox proportional hazards models were fitted to determine mortality up to 36 months., Results: We followed 11,850 suspected cases of CZS, of which 28.3% were confirmed, 9.3% inconclusive and 62.4% unconfirmed. Confirmed cases had almost two times higher mortality when compared with unconfirmed cases. Among unconfirmed cases, we identified three distinct clusters with different mortality trajectories. The highest mortality risk was observed in those with abnormal imaging findings compatible with congenital infections (HR = 12.6; IC95%8.8-18.0) and other abnormalities (HR = 11.6; IC95%8.6-15.6) compared with those with normal imaging findings. The risk was high in those with severe microcephaly (HR = 8.2; IC95%6.4-10.6) and macrocephaly (HR = 6.6; IC95%4.5-9.7) compared with normal head size., Conclusion: Abnormal imaging and head circumference appear to be the main drivers of the increased mortality among suspected cases of CZS. We suggest identifying children who are more likely to die and have a greater need to optimise interventions and resource allocation regardless of the final diagnoses., (© 2022. The Author(s).)

In vertebrates, thyroid hormones are critical players in controlling different physiological processes such as development, growth, metabolism among others. There is evidence in mammals that thyroid hormones are also an important component of the hormonal system that controls reproduction, although studies in fish remain poorly investigated. Here, we tested this hypothesis by investigating the effects of methimazole-induced hypothyroidism on the testicular function in adult zebrafish. Treatment of fish with methimazole, in vivo , significantly altered zebrafish spermatogenesis by inhibiting cell differentiation and meiosis, as well as decreasing the relative number of spermatozoa. The observed impairment of spermatogenesis by methimazole was correlated with significant changes in transcript levels for several genes implicated in the control of reproduction. Using an in vitro approach, we also demonstrated that in addition to affecting the components of the brain-pituitary-peripheral axis, T3 (triiodothyronine) also exerts direct action on the testis. These results reinforce the hypothesis that thyroid hormones are an essential element of multifactorial control of reproduction and testicular function in zebrafish and possibly other vertebrate species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rodrigues, Tovo-Neto, Rosa, Doretto, Fallah, Habibi and Nóbrega.)

Optical biosensors based on localized surface plasmon resonance (LSPR) are the future of label-free detection methods. This work reports the development of plasmonic thin films, containing Au nanoparticles dispersed in a TiO 2 matrix, as platforms for LSPR biosensors. Post-deposition treatments were employed, namely annealing at 400 °C, to develop an LSPR band, and Ar plasma, to improve the sensitivity of the Au-TiO 2 thin film. Streptavidin and biotin conjugated with horseradish peroxidase (HRP) were chosen as the model receptor-analyte, to prove the efficiency of the immobilization method and to demonstrate the potential of the LSPR-based biosensor. The Au-TiO 2 thin films were activated with O 2 plasma, to promote the streptavidin immobilization as a biorecognition element, by increasing the surface hydrophilicity (contact angle drop to 7°). The interaction between biotin and the immobilized streptavidin was confirmed by the detection of HRP activity (average absorbance 1.9 ± 0.6), following a protocol based on enzyme-linked immunosorbent assay (ELISA). Furthermore, an LSPR wavelength shift was detectable (0.8 ± 0.1 nm), resulting from a plasmonic thin-film platform with a refractive index sensitivity estimated to be 33 nm/RIU. The detection of the analyte using these two different methods proves that the functionalization protocol was successful and the Au-TiO 2 thin films have the potential to be used as an LSPR platform for label-free biosensors.

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited., Methods: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age., Results: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome., Conclusions: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.)., (Copyright © 2022 Massachusetts Medical Society.)

Brain iron deficiency (BID) constitutes a primary pathophysiological mechanism in restless legs syndrome (RLS). BID in rodents has been widely used as an animal model of RLS, since it recapitulates key neurochemical changes reported in RLS patients and shows an RLS-like behavioral phenotype. Previous studies with the BID-rodent model of RLS demonstrated increased sensitivity of cortical pyramidal cells to release glutamate from their striatal nerve terminals driving striatal circuits, a correlative finding of the cortical motor hyperexcitability of RLS patients. It was also found that BID in rodents leads to changes in the adenosinergic system, a downregulation of the inhibitory adenosine A 1 receptors (A 1 Rs) and upregulation of the excitatory adenosine A 2A receptors (A 2A Rs). It was then hypothesized, but not proven, that the BID-induced increased sensitivity of cortico-striatal glutamatergic terminals could be induced by a change in A 1 R/A 2A R stoichiometry in favor of A 2A Rs. Here, we used a newly developed FACS-based synaptometric analysis to compare the relative abundance on A 1 Rs and A 2A Rs in cortico-striatal and thalamo-striatal glutamatergic terminals (labeled with vesicular glutamate transporters VGLUT1 and VGLUT2, respectively) of control and BID rats. It could be demonstrated that BID (determined by measuring transferrin receptor density in the brain) is associated with a selective decrease in the A 1 R/A 2A R ratio in VGLUT1 positive-striatal terminals.

This study aimed at introducing thin films exhibiting the localized surface plasmon resonance (LSPR) phenomenon with a reversible optical response to repeated uniaxial strain. The sensing platform was prepared by growing gold (Au) nanoparticles throughout a titanium dioxide dielectric matrix. The thin films were deposited on transparent polymeric substrates, using reactive magnetron sputtering, followed by a low temperature thermal treatment to grow the nanoparticles. The microstructural characterization of the thin films' surface revealed Au nanoparticle with an average size of 15.9 nm, an aspect ratio of 1.29 and an average nearest neighbor nanoparticle at 16.3 nm distance. The plasmonic response of the flexible nanoplasmonic transducers was characterized with custom-made mechanical testing equipment using simultaneous optical transmittance measurements. The higher sensitivity that was obtained at a maximum strain of 6.7%, reached the values of 420 nm/ ε and 110 pp/ ε when measured at the wavelength or transmittance coordinates of the transmittance-LSPR band minimum, respectively. The higher transmittance gauge factor of 4.5 was obtained for a strain of 10.1%. Optical modelling, using discrete dipole approximation, seems to correlate the optical response of the strained thin film sensor to a reduction in the refractive index of the matrix surrounding the gold nanoparticles when uniaxial strain is applied.

The endocannabinoid system is implicated in a plethora of neuropsychiatric disorders. However, it is technically challenging to assess the turnover of 2-arachidonoyl glycerol (2-AG), the principal endocannabinoid molecule in the brain. Two recent studies showed that diacylglycerol lipase α (DAGLα), an enzyme chiefly responsible for the cerebral production of 2-AG, also accepts the surrogate chromogenic substrate 4-nitrophenyl butyrate (4-NPB). Here, we aimed to optimize this spectrophotometric assay for ex vivo brain tissue, in particular, rat cerebrocortical homogenates, to measure the activity of the major enzymes responsible for the production and degradation of 2-AG. The initial velocity of 4-NPB hydrolysis was dependent on protein, substrate, and Ca 2+ concentrations, and was sensitive to the non-selective serine hydrolase inhibitor, methoxy arachidonyl fluorophosphonate, the DAGLα inhibitors, OMDM188, tetrahydrolipstatin, and RHC80267, as well as the monoacylglycerol lipase (MAGL) inhibitor, JZL184, respectively. Next, we tested the usefulness of this assay in ex vivo brain tissue of rat models of human health conditions known to affect cerebrocortical 2-AG production, i.e. pathological stress and sporadic Alzheimer's disease (AD). In rats submitted to chronic restraint stress, cortical CB 1 R density was significantly decreased, as assessed with radioligand binding. Nevertheless, 4-NPB hydrolysis remained at control levels. However, in rats 4 weeks after intracerebroventricular injection with streptozotocin - an established model of sporadic AD -, both CB 1 R levels and 4-NPB hydrolysis and its DAGL- and MAGL-dependent fractions were significantly increased. Altogether, we optimized a simple complementary ex vivo technique for the quantification of DAGL and MAGL activity in brain samples., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Acetic acid is a major inhibitory compound in several industrial bioprocesses, in particular in lignocellulosic yeast biorefineries. Cell envelope remodeling, involving cell wall and plasma membrane composition, structure and function, is among the mechanisms behind yeast adaptation and tolerance to stress. Pdr18 is a plasma membrane ABC transporter of the pleiotropic drug resistance family and a reported determinant of acetic acid tolerance mediating ergosterol transport. This study provides evidence for the impact of Pdr18 expression in yeast cell wall during adaptation to acetic acid stress. The time-course of acetic-acid-induced transcriptional activation of cell wall biosynthetic genes ( FKS1 , BGL2 , CHS3 , GAS1 ) and of increased cell wall stiffness and cell wall polysaccharide content in cells with the PDR18 deleted, compared to parental cells, is reported. Despite the robust and more intense adaptive response of the pdr18 Δ population, the stress-induced increase of cell wall resistance to lyticase activity was below parental strain levels, and the duration of the period required for intracellular pH recovery from acidification and growth resumption was higher in the less tolerant pdr18 Δ population. The ergosterol content, critical for plasma membrane stabilization, suffered a drastic reduction in the first hour of cultivation under acetic acid stress, especially in pdr18 Δ cells. Results revealed a crosstalk between plasma membrane ergosterol content and cell wall biophysical properties, suggesting a coordinated response to counteract the deleterious effects of acetic acid.

In a new era for digital health, dry electrodes for biopotential measurement enable the monitoring of essential vital functions outside of specialized healthcare centers. In this paper, a new type of nanostructured titanium-based thin film is proposed, revealing improved biopotential sensing performance and overcoming several of the limitations of conventional gel-based electrodes such as reusability, durability, biocompatibility, and comfort. The thin films were deposited on stainless steel (SS) discs and polyurethane (PU) substrates to be used as dry electrodes, for non-invasive monitoring of body surface biopotentials. Four different Ti-Me (Me = Al, Cu, Ag, or Au) metallic binary systems were prepared by magnetron sputtering. The morphology of the resulting Ti-Me systems was found to be dependent on the chemical composition of the films, specifically on the type and amount of Me. The existence of crystalline intermetallic phases or glassy amorphous structures also revealed a strong influence on the morphological features developed by the different systems. The electrodes were tested in an in-vivo study on 20 volunteers during sports activity, allowing study of the application-specific characteristics of the dry electrodes, based on Ti-Me intermetallic thin films, and evaluation of the impact of the electrode-skin impedance on biopotential sensing. The electrode-skin impedance results support the reusability and the high degree of reliability of the Ti-Me dry electrodes. The Ti-Al films revealed the least performance as biopotential electrodes, while the Ti-Au system provided excellent results very close to the Ag/AgCl reference electrodes.

Rice bran oil is a highly nutritious vegetable oil, as it is rich in tocols and γ-oryzanol. Degumming is the first step in the vegetable oil refining process, and its main objective is the removal of phospholipids or gums. In the present study, enzymatic degumming trials were performed on crude rice bran oil using the phospholipases PLA1, Purifine ® PLC, their mixture (PLA1/PLC), and a cocktail known as Purifine ® 3G. Enzymatic degumming applying 50 mg/kg of PLA1 for 120 min resulted in a residual phosphorus content of 10.4 mg/kg and an absolute free fatty acid increase of 0.30%. Enzymatic degumming applying 300 mg/kg of Purifine ® PLC for 120 min at 60 °C resulted in a residual phosphorus content of 67 mg/kg and an absolute diacylglycerol increase of 0.41%. The mixture of phospholipases and the cocktail presented approximately 5 mg/kg of residual phosphorus content after the reaction times. For all degumming processes, the preservation of minor components such as tocols and γ-oryzanol were observed. These results indicate that the use of enzyme mixtures or their cocktails to attain low phosphorus content and high diacylglycerol/free fatty acid conversion during enzymatic degumming is a viable alternative.

The microtubule-associated protein tau is implicated in the formation of oligomers and fibrillar aggregates that evade proteostasis control and spread from cell-to-cell. Tau pathology is accompanied by sustained neuroinflammation and, while the release of alarmin mediators aggravates disease at late stages, early inflammatory responses encompass protective functions. This is the case of the Ca 2+ -binding S100B protein, an astrocytic alarmin which is augmented in AD and which has been recently implicated as a proteostasis regulator, acting over amyloid β aggregation. Here we report the activity of S100B as a suppressor of tau aggregation and seeding, operating at sub-stoichiometric conditions. We show that S100B interacts with tau in living cells even in microtubule-destabilizing conditions. Structural analysis revealed that tau undergoes dynamic interactions with S100B, in a Ca 2+ -dependent manner, notably with the aggregation prone repeat segments at the microtubule binding regions. This interaction involves contacts of tau with a cleft formed at the interface of the S100B dimer. Kinetic and mechanistic analysis revealed that S100B inhibits the aggregation of both full-length tau and of the microtubule binding domain, and that this proceeds through effects over primary and secondary nucleation, as confirmed by seeding assays and direct observation of S100B binding to tau oligomers and fibrils. In agreement with a role as an extracellular chaperone and its accumulation near tau positive inclusions, we show that S100B blocks proteopathic tau seeding. Together, our findings establish tau as a client of the S100B chaperone, providing evidence for neuro-protective functions of this inflammatory mediator across different tauopathies., (© 2021. The Author(s).)

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Most AD patients develop the disease in late life, named late onset AD (LOAD). Currently, the most recognized explanation for AD pathology is the amyloid cascade hypothesis. It is assumed that amyloid beta (Aβ) aggregation and deposition are critical pathogenic processes in AD, leading to the formation of amyloid plaques, as well as neurofibrillary tangles, neuronal cell death, synaptic degeneration, and dementia. In LOAD, the causes of Aβ accumulation and neuronal loss are not completely clear. Importantly, the blood-brain barrier (BBB) disruption seems to present an essential role in the induction of neuroinflammation and consequent AD development. In addition, we propose that the systemic inflammation triggered by conditions like metabolic diseases or infections are causative factors of BBB disruption, coexistent inflammatory cascade and, ultimately, the neurodegeneration observed in AD. In this regard, the use of anti-inflammatory molecules could be an interesting strategy to treat, delay or even halt AD onset and progression. Herein, we review the inflammatory cascade and underlying mechanisms involved in AD pathogenesis and revise the anti-inflammatory effects of compounds as emerging therapeutic drugs against AD.

Objective: To evaluate the success and complication rates of ultrasound-guided renal biopsy at a tertiary care hospital., Materials and Methods: This was a retrospective analysis of 97 ultrasound-guided renal biopsies, all performed by the same radiologist, between 1 March, 2017 and 31 October, 2019., Results: Of the 97 biopsies evaluated, 87 had a definitive pathological diagnosis. In five cases (5.4%), the biopsy results were inconclusive and a second procedure was required. In seven procedures (7.6%), there were complications, all of which were properly resolved., Conclusion: Ultrasound-guided renal biopsy has proven to be a safe, effective method for the diagnosis of nephropathies, with high success rates.