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For bioactivity studies, it is necessary to use products with a high degree of purity, which may influence the cytotoxic effects. Supercritical technology presents itself as an alternative to obtain these products. Therefore, the objective of this work was to obtain the bioactive compounds of oil and pulp of açaí fat-free supercritical technology and evaluate the cytotoxicity of products in MRC-5 and VERO cells in vitro. The açaí pulp was subjected to extraction with supercritical CO2 to obtain the oil and pulp without fat, under conditions of 323.15 K at 35 MPa, 333.15 K at 42 MPa, and 343.15 K at 49 MPa. The largest yields (51.74%), carotenoids (277.09 µg/g), DPPH (2.55 μmol TE/g), ABTS (2.60 μmol TE/g), and FRAP (15.25 μm of SF/g) of oil and ABTS (644.23 μmol TE/g) of pulp without fat were found in the condition 343.15 K at 49 MPa. The highest levels of compounds phenolics (150.20 mg GAE/g), DPPH (414.99 μmol TE/g), and FRAP (746.2 μm SF/g) of the pulp without fat were found in the condition of 323.15 K to 35 MPa. The fat-free pulp presented high levels of anthocyanins without significant variation in cytotoxicity. The developed process was efficient in obtaining oil rich in carotenoids, and the supercritical technology elucidated an efficient way to obtain açaí fat-free pulp. [ABSTRACT FROM AUTHOR]

The importance of addressing the problem of biofilms in farm, wild, and companion animals lies in their pervasive impact on animal health and welfare. Biofilms, as resilient communities of microorganisms, pose a persistent challenge in causing infections and complicating treatment strategies. Recognizing and understanding the importance of mitigating biofilm formation is critical to ensuring the welfare of animals in a variety of settings, from farms to the wild and companion animals. Effectively addressing this issue not only improves the overall health of individual animals, but also contributes to the broader goals of sustainable agriculture, wildlife conservation, and responsible pet ownership. This review examines the current understanding of biofilm formation in animal diseases and elucidates the complex processes involved. Recognizing the limitations of traditional antibiotic treatments, mechanisms of resistance associated with biofilms are explored. The focus is on alternative therapeutic strategies to control biofilm, with illuminating case studies providing valuable context and practical insights. In conclusion, the review highlights the importance of exploring emerging approaches to mitigate biofilm formation in animals. It consolidates existing knowledge, highlights gaps in understanding, and encourages further research to address this critical facet of animal health. The comprehensive perspective provided by this review serves as a foundation for future investigations and interventions to improve the management of biofilm-associated infections in diverse animal populations. [ABSTRACT FROM AUTHOR]

Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of β-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% β-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community. [ABSTRACT FROM AUTHOR]

Early and accurate diagnoses of pathogenic microorganisms is essential to correctly identify diseases, treating infections, and tracking disease outbreaks associated with microbial infections, to develop precautionary measures that allow a fast and effective response in epidemics and pandemics, thus improving public health. Aptamers are a class of synthetic nucleic acid molecules with the potential to be used for medical purposes, since they can be directed towards any target molecule. Currently, the use of aptamers has increased because they are a useful tool in the detection of specific targets. We present a brief review of the use of aptamers to detect and identify bacteria or even some toxins with clinical importance. This work describes the advances in the technology of aptamers, with the purpose of providing knowledge to develop new aptamers for diagnoses and treatment of different diseases caused by infectious microorganisms. [ABSTRACT FROM AUTHOR]

This study compared cortical responses to speech in preschoolers with typical language development (TLD) and with Developmental Language Disorder (DLD). We investigated whether top-down language effects modulate speech perception in young children in an adult-like manner. We compared cortical mismatch responses (MMRs) during the passive perception of speech contrasts in three groups of participants: preschoolers with TLD (n = 11), preschoolers with DLD (n = 16), and adults (n = 20). We also measured children's phonological skills and investigated whether they are associated with the cortical discrimination of phonemic changes involving different linguistic complexities. The results indicated top-down language effects in adults, with enhanced cortical discrimination of lexical stimuli but not of non-words. In preschoolers, the TLD and DLD groups did not differ in the MMR measures, and no top-down effects were detected. Moreover, we found no association between MMRs and phonological skills, even though the DLD group's phonological skills were significantly lower. Our findings suggest that top-down language modulations in speech discrimination may not be present during early childhood, and that children with DLD may not exhibit cortical speech perception deficits. The lack of association between phonological and MMR measures indicates that further research is needed to understand the link between language skills and cortical activity in preschoolers. [ABSTRACT FROM AUTHOR]

The effect of current density and bath temperature in the electroplating process on resistance to corrosion of Zn-Ni alloys was evaluated in this work. The electrolytic bath consisted of nickel sulfate, zinc sulfate, sodium sulfate, boric acid, and sodium citrate at pH 7.0. The current density was varied in the range 20–80 mA/cm2 and the bath temperature in the range 30–60 °C. Increasing, independently, the current density or the bath temperature increased the nickel content in the obtained alloy, which affected the alloy microstructure, with a predominant γ phase and cauliflower-like morphology. The nickel content in the alloys was in the range 20–42%wt. A synergistic effect between the current density and bath temperature was observed from a design of experiments and response surface models. The maximum resistance to corrosion occurred for the alloy containing 42%wt. nickel. This alloy was obtained at upper levels of current density and bath temperature, presenting a corrosion potential of −0.789 V and polarization resistance of 4136 Ω.cm2. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea is a sleep disorder with a high prevalence in the world population. The mandibular advancement device is one of the options for treating obstructive sleep apnea. Neck computed tomography and drug-induced sleep endoscopy are complementary diagnostic tests that may help predict the effectiveness of mandibular advancement devices. This study aims to analyze the best method for predicting the effectiveness of mandibular advancement devices in the therapeutic approach to obstructive sleep apnea. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection databases will be comprehensively searched. We will include randomized clinical trials, non-randomized prospective or retrospective clinical studies, case controls, cohort studies, and case series. Two authors will independently conduct data extraction and assess the literature quality of the studies. The analysis of the included literature will be conducted by Revman 5.3 software. The outcomes that will be analyzed are craniofacial characteristics, cephalometric assessments, site and type of obstruction of the upper airway, mean values of the apnea–hypopnea index, and SaO2 verified in the initial and follow-up polysomnography. This study will provide reliable, evidence-based support for the clinical application of mandibular advancement devices for obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

This study aims to manufacture and characterize titanium and nickel alloys with different molybdenum (Ti–Ni–Mo) contents, focusing on the influence of these additions on the microstructure, mechanical properties, and corrosion resistance. The relevance of this work stems from the lack of research on this specific alloy and the absence of reports in the literature with molybdenum percentages above 2 at.%. Ti50Ni50−XMox alloys were produced by the plasma arc melting method, with six different compositions (x = 0, 0.5, 1, 2, 3, and 4 at.% Mo), and a comprehensive analysis of microstructure, chemical composition, thermal, mechanical, and electrochemical properties was carried out. The results demonstrated significant alterations in the microstructure of the Ni–Ti alloy with the addition of molybdenum presenting several phases, precipitates (TiNi, Ti2Ni), and oxides (Ti4Ni2O, TiO, and TiO3). The stability of the B2 phase increased with molybdenum content, and the monoclinic martensite (B19′) phase was identified only in the Ni–Ti sample. Introducing molybdenum into the Ni–Ti alloy generated the R-phase and shifted the phase transformation peaks to lower temperatures, as differential scanning calorimetry (DSC) indicated. Microhardness and elastic modulus decreased with increasing Mo content, ranging from 494 HV to 272 HV and 74 GPa to 63 GPa, respectively. Corrosion tests revealed increased corrosion resistance with increasing Mo content, reaching a polarization resistance of 2710 kΩ·cm2 and corrosion current of 11.3 µA. Therefore, this study points to Ti–Ni–Mo alloys as potential candidates to increase the range of Ni–Ti alloy applications, mainly in biomaterials, reinforcing its relevance and need in current alloy research. [ABSTRACT FROM AUTHOR]

Parents play a significant role in adolescent health behaviors; however, few nutrition interventions for Hispanic adolescents involve parents. This study assessed the effects of a 10-week parenting intervention simultaneously targeting nutrition and substance use prevention. Hispanic parent/6th–8th-grade adolescent dyads (n = 239) were randomized to Families Preparing the New Generation Plus (FPNG+; nutrition/substance use prevention), FPNG (substance use prevention only), or Realizing the American Dream (RAD; academic success control). Surveys assessed diet, alcohol use, substance use intentions, and substance use norms at baseline (T1), immediately post-intervention (T2), and at 16 weeks post-intervention (T3). Latent change modeling assessed diet changes; adolescent substance use outcomes were assessed using effect sizes. Among adolescents, those in FPNG+ increased fruit (+0.32 cup equivalents, p = 0.022) and fiber intake (+1.06 g, p = 0.048) and did not change added sugars intake at T2; those in FPNG and RAD reduced their intake of fruit and fiber (p < 0.05 for both). FPNG+ parents marginally increased fruit/vegetable intake (+0.17 cup equivalents, p = 0.054) and increased whole grains intake (+0.25-ounce equivalents, p < 0.05), in contrast to the reduction among RAD and FPNG parents (p < 0.05). Reductions in added sugar intake at T2 were greater among FPNG and FPNG+ parents relative to RAD parents (p < 0.05). FPNG+ and FPNG had comparable substance use outcomes (i.e., both had lower alcohol use and intentions to use substances relative to RAD). Engaging parents in a nutrition and substance use prevention parenting intervention yielded positive changes in dietary intake and maintained substance use prevention outcomes among their adolescent children. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, several hospitals have incorporated MRI equipment managed directly by their cardiology departments. The aim of our work is to determine the total cost per test of both CT and MRI in the setting of a Cardiology Department of a tertiary hospital. Materials and Methods: The process followed for estimating the costs of CT and MRI tests consists of three phases: (1) Identification of the phases of the testing process; (2) Identification of the resources consumed in carrying out the tests; (3) Quantification and assessment of inputs. Results: MRI involves higher personnel (EUR 66.03 vs. EUR 49.17) and equipment (EUR 89.98 vs. EUR 33.73) costs, while CT consumes higher expenditures in consumables (EUR 93.28 vs. EUR 22.95) and overheads (EUR 1.64 vs. EUR 1.55). The total cost of performing each test is higher in MRI (EUR 180.60 vs. EUR 177.73). Conclusions: We can conclude that the unit cost of each CT and MRI performed in that unit are EUR 177.73 and EUR 180.60, respectively, attributable to consumables in the case of CT and to amortization of equipment and staff time in the case of MRI. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms responsible for anxiety disorders is a major challenge. Avoidance behavior is an essential feature of anxiety disorders. The two-way avoidance test is a preclinical model with two distinct subpopulations—the good and poor performers—based on the number of avoidance responses presented during testing. It is believed that the habenula subnuclei could be important for the elaboration of avoidance response with a distinct pattern of activation and neuroinflammation. The present study aimed to shed light on the habenula subnuclei signature in avoidance behavior, evaluating the pattern of neuronal activation using FOS expression and astrocyte density using GFAP immunoreactivity, and comparing control, good and poor performers. Our results showed that good performers had a decrease in FOS immunoreactivity (IR) in the superior part of the medial division of habenula (MHbS) and an increase in the marginal part of the lateral subdivision of lateral habenula (LHbLMg). Poor performers showed an increase in FOS in the basal part of the lateral subdivision of lateral habenula (LHbLB). Considering the astroglial immunoreactivity, the poor performers showed an increase in GFAP-IR in the inferior portion of the medial complex (MHbl), while the good performers showed a decrease in the oval part of the lateral part of the lateral complex (LHbLO) in comparison with the other groups. Taken together, our data suggest that specific subdivisions of the MHb and LHb have different activation patterns and astroglial immunoreactivity in good and poor performers. This study could contribute to understanding the neurobiological mechanisms responsible for anxiety disorders. [ABSTRACT FROM AUTHOR]

Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrβ: β1, β2 and β3). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrβ3 (Adrβ3KO) with consequent inhibition of sustained glial-mediated inflammation. To test this, 21- and 86-day-old Adrβ3KO mice were exposed to an 8-week multisensory stimulation (MS) protocol that comprised gustatory and olfactory stimuli of positive and negative valence; intellectual challenges to reach food; the use of hidden objects; and the presentation of food in ways that prompted foraging, which was followed by analysis of GFAP, Iba-1 and EAAT2 protein expression in the hippocampus (HC) and amygdala (AMY). The MS protocol reduced GFAP and Iba-1 expression in the HC of young mice but not in older mice. While this protocol restored memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsened the memory of Adrβ3KO mice. In the AMY of Adrβ3KO older mice, we observed an increase in GFAP and EAAT2 expression when compared to wild-type (WT) mice that MS was unable to reduce. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied immediately after weaning in Adrβ3KO animals and indicates that the control of neuroinflammation mediates this response. [ABSTRACT FROM AUTHOR]

Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1β in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased β-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic β-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic β-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain. [ABSTRACT FROM AUTHOR]

Swine pathogenic infection caused by Escherichia coli, known as swine colibacillosis, represents an epidemiological challenge not only for animal husbandry but also for health authorities. To note, virulent E. coli strains might be transmitted, and also cause disease, in humans. In the last decades, diverse successful multidrug-resistant strains have been detected, mainly due to the growing selective pressure of antibiotic use, in which animal practices have played a relevant role. In fact, according to the different features and particular virulence factor combination, there are four different pathotypes of E. coli that can cause illness in swine: enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC) that comprises edema disease E. coli (EDEC) and enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and extraintestinal pathogenic E. coli (ExPEC). Nevertheless, the most relevant pathotype in a colibacillosis scenario is ETEC, responsible for neonatal and postweaning diarrhea (PWD), in which some ETEC strains present enhanced fitness and pathogenicity. To explore the distribution of pathogenic ETEC in swine farms and their diversity, resistance, and virulence profiles, this review summarizes the most relevant works on these subjects over the past 10 years and discusses the importance of these bacteria as zoonotic agents. [ABSTRACT FROM AUTHOR]

Prescription drug misuse (PDM) has become a major health issue in the U.S. over the past decade. PDM affects all ethnic and racial groups; however, there is a higher prevalence among American Indian (AI) youths, and there is scarce information on the risk and protective factors driving this behavior. Using the Arizona Youth Survey 2018, we analyzed data from 2494 students who self-identified as AI (aged 13–18 years, 47.31% male). Logistic regression models were used to examine the association between community attachment with lifetime and the past-30-days PDM. Community attachment was negatively associated with AI youths' lifetime PDM (OR = 0.78, 95% CI [0.65, 0.92]); however, it was not significant for the past-30-days users (OR = 0.91, 95% CI [0.72, 1.15]). For both lifetime and past-30-days users, a common protective factor was close friends' negative perceptions of PDM, while a common risk factor included siblings' prescription drug use and ease of access to substances. Lifetime users' drug-free closest friends were also protective. The findings support similar community-oriented approaches showing a cumulative rather than immediate effect, and past-30-days PMD youths were strongly influenced by peers and family. PDM risk and protective factors can advance knowledge about AI youths' social and cultural determinants of health and influence future prevention interventions. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. Results: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition. [ABSTRACT FROM AUTHOR]

Due to its several economic and ecological consequences, biofouling is a widely recognized concern in the marine sector. The search for non-biocide-release antifouling coatings has been on the rise, with carbon-nanocoated surfaces showing promising activity. This work aimed to study the impact of pristine graphene nanoplatelets (GNP) on biofilm development through the representative marine bacteria Cobetia marina and to investigate the antibacterial mechanisms of action of this material. For this purpose, a flow cytometric analysis was performed and a GNP/polydimethylsiloxane (PDMS) surface containing 5 wt% GNP (G5/PDMS) was produced, characterized, and assessed regarding its biofilm mitigation potential over 42 days in controlled hydrodynamic conditions that mimic marine environments. Flow cytometry revealed membrane damage, greater metabolic activity, and endogenous reactive oxygen species (ROS) production by C. marina when exposed to GNP 5% (w/v) for 24 h. In addition, C. marina biofilms formed on G5/PDMS showed consistently lower cell count and thickness (up to 43% reductions) than PDMS. Biofilm architecture analysis indicated that mature biofilms developed on the graphene-based surface had fewer empty spaces (34% reduction) and reduced biovolume (25% reduction) compared to PDMS. Overall, the GNP-based surface inhibited C. marina biofilm development, showing promising potential as a marine antifouling coating. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity. [ABSTRACT FROM AUTHOR]

Background: Inflammation is a complex process as a response to several stimuli, such as infection, a chemical irritant, and the attack of a foreign body. Piquerol was isolated from Piqueria trinervia, and its anti-inflammatory activity was evaluated using in vivo and in vitro models. Methods: Piquerol is a monoterpene that was identified using NMR, FT-IR spectroscopy, and mass spectrometry analysis. The anti-inflammatory activity was tested in vivo in ear edema induced with TPA in mice. Piquerol was also tested on J774A.1 macrophages stimulated with lipopolysaccharide (LPS), and the levels of NO, NF-κB, TNF-α, IL-1β, IL-6, and IL-10 were determined using ELISA. Results: The results show that piquerol diminished ear edema (66.19%). At 150.51 µM, it also inhibited the levels of NO (31.7%), TNF-α (49.8%), IL-1β (69.9%), IL-6 (47.5%), and NF-κB (26.7%), and increased the production of IL-10 (62.3%). Piquerol has a membrane stabilization property in erythrocyte, and at 100 µg/mL, the membrane protection was of 86.17%. Conclusions: Piquerol has anti-inflammatory activity, and its possible mechanism of action is through the inhibition of pro-inflammatory mediators. This compound could be a candidate in the development of new drugs to treat inflammatory problems. [ABSTRACT FROM AUTHOR]

Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disorder (ND). While most research in NDs has been following a neuron-centric point of view, microglia are now recognized as crucial in the brain. Previous work revealed alterations that point to an increased activation state of microglia in the brain of CMVMJD135 mice, a MJD mouse model that replicates the motor symptoms and neuropathology of the human condition. Here, we investigated the extent to which microglia are actively contributing to MJD pathogenesis and symptom progression. For this, we used PLX3397 to reduce the number of microglia in the brain of CMVMJD135 mice. In addition, a set of statistical and machine learning models were further implemented to analyze the impact of PLX3397 on the morphology of the surviving microglia. Then, a battery of behavioral tests was used to evaluate the impact of microglial depletion on the motor phenotype of CMVMJD135 mice. Although PLX3397 treatment substantially reduced microglia density in the affected brain regions, it did not affect the motor deficits seen in CMVMJD135 mice. In addition to reducing the number of microglia, the treatment with PLX3397 induced morphological changes suggestive of activation in the surviving microglia, the microglia of wild-type animals becoming similar to those of CMVMJD135 animals. These results suggest that microglial cells are not key contributors for MJD progression. Furthermore, the impact of PLX3397 on microglial activation should be taken into account in the interpretation of findings of ND modification seen upon treatment with this CSF1R inhibitor. [ABSTRACT FROM AUTHOR]

Simple Summary: The local conditions of tumor cell growth, known as the tumor microenvironment (TME), are characterized by low oxygen supply (hypoxia) caused by insufficient blood delivery. Hypoxic cancers have a strong invasive potential, metastasis, resistance to therapy, and a poor clinical prognosis. The use of supplemental oxygen, known as hyperoxia, has been described to diminish the hypoxic state and to achieve a better response to different treatments. Here, we provide an overview of how hyperoxia interacts with other therapies decreasing tumor progression and the negative effects of the use of high oxygen levels. We also perform an analysis, showing the differences in the patterns of expression between a tumor-derived cell line and a nonmalignant cell line. Hyperoxia is used in order to counteract hypoxia effects in the TME (tumor microenvironment), which are described to boost the malignant tumor phenotype and poor prognosis. The reduction of tumor hypoxic state through the formation of a non-aberrant vasculature or an increase in the toxicity of the therapeutic agent improves the efficacy of therapies such as chemotherapy. Radiotherapy efficacy has also improved, where apoptotic mechanisms seem to be implicated. Moreover, hyperoxia increases the antitumor immunity through diverse pathways, leading to an immunopermissive TME. Although hyperoxia is an approved treatment for preventing and treating hypoxemia, it has harmful side-effects. Prolonged exposure to high oxygen levels may cause acute lung injury, characterized by an exacerbated immune response, and the destruction of the alveolar–capillary barrier. Furthermore, under this situation, the high concentration of ROS may cause toxicity that will lead not only to cell death but also to an increase in chemoattractant and proinflammatory cytokine secretion. This would end in a lung leukocyte recruitment and, therefore, lung damage. Moreover, unregulated inflammation causes different consequences promoting tumor development and metastasis. This process is known as protumor inflammation, where different cell types and molecules are implicated; for instance, IL-1β has been described as a key cytokine. Although current results show benefits over cancer therapies using hyperoxia, further studies need to be conducted, not only to improve tumor regression, but also to prevent its collateral damage. [ABSTRACT FROM AUTHOR]

A fast and sensitive method that is based on Ultra High Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry (UHPLC-HRMS) for the measurement of Sulfavant A, a molecular adjuvant with a sulfolipid skeleton, is described. The method has been validated over the linearity range of 2.5–2000 ngmL−1 using a deuterated derivative (d70-Sulfavant A) as internal standard. Chromatographic separation is based on a UHPLC Kinetex® 2.6 µm PS C18 column and a gradient of methanol in 0.32 mM ammonium hydroxide solution buffered at pH 8. The lowest limit of quantification of Sulfavant A was 6.5 ngmL−1. The analytical procedure was tested on an extract of mice lung spiked with 30, 300, and 1500 ng of Sulfavant A. The analysis revealed a precision and accuracy value (as a mean value of all the quality control samples analyzed) of 4.7% and 96% in MeOH and 6.4% and 93.4% in the lung extracts, respectively. [ABSTRACT FROM AUTHOR]

Molecular complexation is a strategy used to modify the physicochemical or biopharmaceutical properties of an active pharmaceutical ingredient. Solvent assisted grinding is a common method used to obtain solid complexes in the form of cocrystals. Lidocaine is a drug used as an anesthetic and for the treatment of chronic pain, which bears in its chemical structure an amide functional group able to form hydrogen bonds. Polyphenols are used as cocrystal coformers due to their ability to form O-H...X (X = O, N) hydrogen bond interactions. The objective of this study was to exploit the ability of phloroglucinol to form molecular complexes with lidocaine by liquid assisted grinding. The formation of the complex was confirmed by the shift of the O-H and C=O stretching bands in the IR spectra of the polycrystalline ground powders, suggesting the formation of O-H...O=C hydrogen bonds. Hydration of the complexes also was confirmed by IR spectroscopy and by powder X-ray diffraction. The molecular structure was determined by single crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

Intramolecular hydrogen bond (HB) formation was analyzed in the model compounds N-(2-benzoylphenyl)acetamide, N-(2-benzoylphenyl)oxalamate and N1,N2-bis(2-benzoylphenyl)oxalamide. The formation of three-center hydrogen bonds in oxalyl derivatives was demonstrated in the solid state by the X-ray diffraction analysis of the geometric parameters associated with the molecular structures. The solvent effect on the chemical shift of H6 [δH6(DMSO-d6)–δH6(CDCl3)] and Δδ(ΝΗ)/ΔT measurements, in DMSO-d6 as solvent, have been used to establish the energetics associated with intramolecular hydrogen bonding. Two center intramolecular HB is not allowed in N-(2-benzoylphenyl)acetamide either in the solid state or in DMSO-d6 solution because of the unfavorable steric effects of the o-benzoyl group. The estimated ΔH° and ΔS° values for the hydrogen bonding disruption by DMSO-d6 of 28.3(0.1) kJ·mol-1 and 69.1(0.4) J·mol-1·K-1 for oxalamide, are in agreement with intramolecular three-center hydrogen bonding in solution. In the solid, the benzoyl group contributes to develop 1-D and 2-D crystal networks, through C–H•••A (A = O, π) and dipolar C=O•••A (A = CO, π) interactions, in oxalyl derivatives. To the best of our knowledge, this is the first example where three-center hydrogen bond is claimed to overcome steric constraints. [ABSTRACT FROM AUTHOR]

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ▵ KNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ▵ KNHO and ▵ ▵ G°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization. [ABSTRACT FROM AUTHOR]

The in vitro antioxidant activities of eight 3-carboxycoumarin derivatives were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazil (DPPH•) radical scavenging activity method. 3-Acetyl-6-hydroxy-2H-1-benzopyran-2-one (C1) and ethyl 6-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate (C2) presented the best radical-scavenging activity. A quantitative structure-activity relationship (QSAR) study was performed and correlated with the experimental DPPH• scavenging data. We used structural, geometrical, topological and quantum-chemical descriptors selected with Genetic Algorithms in order to determine which of these parameters are responsible of the observed DPPH• radical scavenging activity. We constructed a back propagation neural network with the hydrophilic factor (Hy) descriptor to generate an adequate architecture of neurons for the system description. The mathematical model showed a multiple determination coefficient of 0.9196 and a root mean squared error of 0.0851. Our results shows that the presence of hydroxyl groups on the ring structure of 3-carboxy-coumarins are correlated with the observed DPPH• radical scavenging activity effects. [ABSTRACT FROM AUTHOR]

In vitro antioxidant activity for 12 stannoxanes derived from Ph3SnCl (compounds 1-3), Ph2SnCl2 (compounds 4-6), Bu3SnCl (compounds 7-9), and Bu2SnCl2 (compounds 10-12), was assayed qualitatively by the chromatographic profile with 1,1- diphenyl-2-picrylhydrazil (DPPH) method and by two quantitative methods: the DPPH radical scavenging activity and Ferric-Reducing Antioxidant Power (FRAP) assays. The results were compared with those obtained with the starting materials 2-pyridinecarboxylic acid (I), 3-pyridinecarboxylic acid (II) and 4-pyridinecarboxylic acid (III), as well as with standard compounds, such as vitamin C and vitamin E, respectively. The in vitro antiradical activity with DPPH of diphenyltin derivative 5 showed a very similar behavior to vitamin C at a 20 μg//mL concentration, whereas according to the FRAP method, compound 8 was better. This difference is due to the mechanism of the antioxidant process. The Structure-Activity Relationships (SAR) for both methods is also reported . [ABSTRACT FROM AUTHOR]

Microglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado–Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultures and microglial cells obtained from disease-relevant brain regions of neonatal and adult CMVMJD135 mice, respectively. Machine learning models were implemented to identify potential clusters of microglia based on their morphological features, and an RNA-sequencing analysis was performed to identify molecular perturbations and potential therapeutic targets. Our findings reveal morphological alterations that point to an increased activation state of microglia in CMVMJD135 mice and a disease-specific transcriptional profile of MJD microglia, encompassing a total of 101 differentially expressed genes, with enrichment in molecular pathways related to oxidative stress, immune response, cell proliferation, cell death, and lipid metabolism. Overall, these results allowed us to define the cellular and molecular profile of MJD-associated microglia and to identify genes and pathways that might represent potential therapeutic targets for this disorder. [ABSTRACT FROM AUTHOR]

Exploring the contextualized relationship between conflict and household resilience is a key element of policymaking under the Humanitarian and Development nexus. This paper provides new evidence on conflict and resilience from resilience-enhancing projects in Mali's Central Sahel cross-border area. In particular, it explores the presence of determinants of resilience that explains conflict exposure; investigates the adoption of conflict-specific coping mechanisms and explores contextual specificities of local resilience capacity. The findings show that certain types of agricultural households have a higher probability of exposure to conflict, while no evidence of public transfers (e.g., cash transfers) increasing the level of exposure to conflicts is found. The results also show that there are elements which explain the adoption (or lack thereof) of coping mechanisms against conflict: social networks play an essential enabling role, as well as education, the level of food consumption, and to some extent, access to public transfers. Finally, the results suggest that female-headed households need more support in order to engage in coping strategies. This paper suggests that resilience-enhancing interventions and analysis require deeper knowledge of the context, paying special attention to the drivers of conflict and coping strategies adopted by households. [ABSTRACT FROM AUTHOR]

Persistent pain is a prevalent symptom of Parkinson's disease (PD), which is related to the loss of monoamines and neuroinflammation. Motor cortex stimulation (MCS) inhibits persistent pain by activating the descending analgesic pathways; however, its effectiveness in the control of PD-induced pain remains unclear. Here, we evaluated the analgesic efficacy of MCS together with serotonergic and spinal glial modulation in an experimental PD (ePD) rat model. Wistar rats with unilateral striatal 6-OHDA and MCS were assessed for behavioral immobility and nociceptive responses. The immunoreactivity of dopamine in the substantia nigra and serotonin in the nucleus raphe magnus (NRM) and the neuronal, astrocytic, and microglial activation in the dorsal horn of the spinal cord were evaluated. MCS, without interfering with dopamine loss, reversed ePD-induced immobility and hypernociception. This response was accompanied by an exacerbated increase in serotonin in the NRM and a decrease in neuronal and astrocytic hyperactivation in the spinal cord, without inhibiting ePD-induced microglial hypertrophy and hyperplasia. Taken together, MCS induces analgesia in the ePD model, while restores the descending serotonergic pathway with consequent inhibition of spinal neurons and astrocytes, showing the role of MCS in PD-induced pain control. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the analytical and clinical performance of the SARS-CoV-2 molecular detection kits used in Argentina. Nine real-time reverse-transcription polymerase chain reaction (RT-qPCR) and three reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays were evaluated using the World Health Organization (WHO) recommended test as reference method. A secondary standard calibrated for the E, N and RdRp genes against the Pan American Health Organization—World Health Organization—International Standard was used to calculate the limit of detection (LoD). A panel of artificial clinical samples, 32 positive and 30 negative for SARS-CoV-2, were analyzed to estimate the kappa concordance (κ) and the diagnostic performance. Differences among the LoD values for the target genes amplified by each kit were >1 log copies/reaction. The κ for the RT-qPCR kits was greater than 0.9, whereas that for the RT-LAMP assays ranged from 0.75 to 0.93. The clinical performance of RT-qPCR kits showed 100% specificity and high sensitivity, although with variations according to the gene analyzed. The E and N genes provided greater clinical sensitivity, whereas the RdRp gene increased the clinical specificity. The RT-LAMP assays revealed a variable diagnostic performance. The information provided can be useful to choose the most appropriate diagnostic test and may contribute to the establishment of a consensus in the diagnosis of SARS-CoV-2 in Argentina and the region. [ABSTRACT FROM AUTHOR]

Bovine papillomavirus (BPV) can cause damage to the epithelial and mucosal tissue and currently presents 28 known types. Not all BPV types are associated with the development of cancer in cattle. Studies have shown that variants of human papillomavirus types can present different pathogenic profiles. However, despite the similarity, it is not yet known whether variants of BPV types can also present varying degrees of pathogenicity. Thus, the aim of this study was to evaluate the genetic variability of BPV types and variants isolated in Northeastern Brazil. Samples were obtained from animals with papillomatous lesions. BPV DNA was detected by the amplification of the L1 gene and genotyping was performed by sequencing. Mutations were analyzed in a phylogenetic, structural and functional context. In total, 52 positive samples were obtained and 11 different BPV types were identified in the samples. Ten putative new BPV types were also identified. In addition, several non-synonymous mutations were identified and predicted to alter protein stability, having an impact on immune evasion. The study demonstrated a high genetic diversity of BPV in the region with a large number of mutations identified, serving as a basis for more efficient control measures to be adopted for bovine papillomatosis. [ABSTRACT FROM AUTHOR]

Escherichia coli ST131 is a clinical challenge due to its multidrug resistant profile and successful global spread. They are often associated with complicated infections, particularly urinary tract infections (UTIs). Bacteriocins play an important role to outcompete other microorganisms present in the human gut. Here, we characterized bacteriocin-encoding plasmids found in ST131 isolates of patients suffering from a UTI using both short- and long-read sequencing. Colicins Ia, Ib and E1, and microcin V, were identified among plasmids that also contained resistance and virulence genes. To investigate if the potential transmission range of the colicin E1 plasmid is influenced by the presence of a resistance gene, we constructed a strain containing a plasmid which had both the colicin E1 and blaCMY-2 genes. No difference in transmission range was found between transformant and wild-type strains. However, a statistically significantly difference was found in adhesion and invasion ability. Bacteriocin-producing isolates from both ST131 and non-ST131 lineages were able to inhibit the growth of other E. coli isolates, including other ST131. In summary, plasmids harboring bacteriocins give additional advantages for highly virulent and resistant ST131 isolates, improving the ability of these isolates to compete with other microbiota for a niche and thereby increasing the risk of infection. [ABSTRACT FROM AUTHOR]

The environment protection has been the starting point for the development of new technologies, which allow the control of highly toxic substances present in the effluents of various industries, whose removal is not feasible by conventional methods. In this research, mixed oxide catalysts Mn and Cu in different molar ratios were prepared from the autocombustion method and characterized by XRD, XRF, TPR-H2, and N2 adsorption–desorption isotherms. The solids were evaluated in the catalytic wet peroxide oxidation of crystal violet (CV) with mild conditions of reaction: 25 °C, normal pressure, airflow of 2 mL/min, and H2O2 0.1 M (2 mL/h). The experimental results indicated degradations of 100% of CV, conversion of the total organic carbon (TOC) of 74%, and elimination of chemical oxygen demand (COD) of 71% in 90 min of reaction. Additionally, the selectivity was monitored by CG-MS, finding that there was almost complete mineralization in a short reaction time, generating intermediate products such as carboxylic acids, alcohols, and amines that do not cause a serious risk to the environment. The Mn–Cu catalyst with molar ratios of 1:2 was the most promising catalyst, displaying a cooperative effect between the two metals, and demonstrating the importance of the redox properties for the elimination of CV dye in wastewater. [ABSTRACT FROM AUTHOR]

Annona purpurea, known in Mexico as "cabeza de negro" or "ilama", belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A–E (1–5). These compounds have an aliphatic chain of 37 carbons with a terminal α,β unsaturated γ-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) α-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF α,α'-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1–4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM). [ABSTRACT FROM AUTHOR]

This study compared cortical responses to speech in preschoolers with typical language development (TLD) and with Developmental Language Disorder (DLD). We investigated whether top-down language effects modulate speech perception in young children in an adult-like manner. We compared cortical mismatch responses (MMRs) during the passive perception of speech contrasts in three groups of participants: preschoolers with TLD (n = 11), preschoolers with DLD (n = 16), and adults (n = 20). We also measured children's phonological skills and investigated whether they are associated with the cortical discrimination of phonemic changes involving different linguistic complexities. The results indicated top-down language effects in adults, with enhanced cortical discrimination of lexical stimuli but not of non-words. In preschoolers, the TLD and DLD groups did not differ in the MMR measures, and no top-down effects were detected. Moreover, we found no association between MMRs and phonological skills, even though the DLD group's phonological skills were significantly lower. Our findings suggest that top-down language modulations in speech discrimination may not be present during early childhood, and that children with DLD may not exhibit cortical speech perception deficits. The lack of association between phonological and MMR measures indicates that further research is needed to understand the link between language skills and cortical activity in preschoolers.

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization.

The aim of the present study was to estimate the prevalence of toothaches and to evaluate its effects on the daily lives of adults living in an industrialised region of southeastern Brazil. A questionnaire was administered to a sample of 744 individuals. The variables related to toothache were grouped into three components: access to dental service, pain severity, and social/functional impacts. The present study found that 68.0% of the subjects had limited access to oral health care, 39.7% presented high toothache severity, and 47.3% reported that toothache greatly affected their daily lives. Nervousness (87.2%) and chewing difficulty (72.6%) were the most commonly reported toothache-related effects. Through correspondence analysis, four groups with separate profiles for toothache and associated factors were identified. Two groups reported greater effects of toothaches in their daily lives. One group consisted of individuals who had less access to dental services (women and individuals who were multiracial, married, had a middle school education, or a low family income). The other group consisted of individuals who reported a high toothache severity and high degree of social/functional impacts (individuals who were 40 to 44 years old, married or widowed, black or multiracial, and had a middle school education). The other two groups were those whose daily lives were less affected by toothaches. One group consisted of individuals who had greater access to dental services (men and individuals who were divorced, had a college degree, or had incomes greater than R$ 300.01). The final group consisted of individuals who had low toothache severity and a low degree of associated social/functional impacts (individuals who were 35 to 39 years old, white, single, or had a high school education).