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Geography allows for the use of a significant diversity of pedagogical-didactic strategies. Therefore, this article explores the application of data analysis in Geography education, specifically focusing on the theme of “Development Contrasts” in the 9th grade, aiming to understand if the utilization of this strategy leads to an improvement in student learning outcomes. Methodologically, the study encompassed three distinct phases across four classes, with the participation of 73 students, employing survey questionnaires to assess satisfaction levels and assignments to gauge the effectiveness of learning. The primary trend revealed by the results suggests that this approach significantly contributes to enhancing student learning in Geography. [ABSTRACT FROM AUTHOR]

Purpose: New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68 Ga-NOTA-HER3P1 PET/MRI for prediction of early response to pan-RTKIs in gastric cancer (GCa).Procedures: GCa cell lines were evaluated for expression of RTKs, and downstream signaling pathways (AKT and MAPK). Cell viability was assessed following 24-72 h of treatment with 0.01-1 µmol/L of afatinib, a pan-RTKI. HER3-expressing afatinib-sensitive (NCI-N87) and resistant cells (SNU16) were selected for evaluation of changes in RTKs expression and downstream pathways, with 24-72 h of 0.1 µmol/L afatinib treatment. 68 Ga-NOTA-HER3P1 PET/MRI was performed in subcutaneous NCI-N87 and SNU16 xenografts (nu:nu, n = 12/group) at baseline and 4 days after afatinib treatment (10 mg/kg, PO, daily). Temporal changes in PET measures were correlated to HER3 expression in tumors, tumor growth rate, and treatment response.Results: With afatinib therapy, NCI-N87 cells showed increased total HER3 expression, and reduction of other RTKs and downstream nodes within 72 h, while SNU16 cells showed no significant change in total HER3 and downstream nodes. 68 Ga-HER3P1 PET/MRI showed increased uptake in NCI-N87 and no significant change in SNU16 tumors (day 4 vs. baseline SUVmean: 3.8 ± 0.7 vs. 1.6 ± 0.6, p < 0.05 in NCI-N87, and 1.5 ± 0.7 vs. 1.7 ± 0.7, p > 0.05 in SNU16). These findings were in concordance with HER3 expression in histopathological analyses and tumor growth over 3 weeks of treatment (mean tumor volume in treated vs. control: 11 ± 17 mm3 vs. 293 ± 79 mm3, p < 0.001 in NCI-N87, and 238 ± 91 mm3 vs. 282 ± 35 mm3, p > 0.05 in SNU16).Conclusions: Quantitative changes in HER3 PET could be used to predict response to pan-RTKI within few days after initiation of treatment and can help with personalizing GCa management. [ABSTRACT FROM AUTHOR]

NorA is one of the main native MDR efflux pumps of Staphylococcus aureus, contributing to reduced susceptibility towards fluoroquinolones and biocides, but little is known about its variability within S. aureus or its distribution and conservation among other staphylococci. We screened for sequences homologous to S. aureus norA and found it in 61 out of the 63 Staphylococcus species described. To the best of our knowledge, this is the first study to report the occurrence of norA across the Staphylococcus genus. The norA phylogenetic tree follows the evolutionary relations of staphylococci and the closely related Mammalliicoccus genus. Comparative analyses suggest a conservation of the NorA function in staphylococci. We also analyzed the variability of norA within S. aureus, for which there are several circulating norA alleles, differing up to 10% at the nucleotide level, which may hamper proper norA detection. We demonstrate the applicability of a PCR-based algorithm to detect and differentiate norA alleles in 52 S. aureus representing a wider collection of 89 isolates from different hosts. Our results highlight the prevalence of norAI and norAII in different settings and the association of norA alleles with specific S. aureus clonal lineages. Ultimately, it confirms the applicability of our PCR-based algorithm to rapidly detect and assign the different norA alleles, a trait that may impact antimicrobial efflux capacity and the search for potential NorA inhibitors. [ABSTRACT FROM AUTHOR]

The use of electrospun meshes has been proposed as highly efficient protective equipment to prevent respiratory infections. Those infections can result from the activity of micro-organisms and other small dust particles, such as those resulting from air pollution, that impair the respiratory tract, induce cellular damage and compromise breathing capacity. Therefore, electrospun meshes can contribute to promoting air-breathing quality and controlling the spread of such epidemic-disrupting agents due to their intrinsic characteristics, namely, low pore size, and high porosity and surface area. In this review, the mechanisms behind the pathogenesis of several stressors of the respiratory system are covered as well as the strategies adopted to inhibit their action. The main goal is to discuss the performance of antimicrobial electrospun nanofibers by comparing the results already reported in the literature. Further, the main aspects of the certification of filtering systems are highlighted, and the expected technology developments in the industry are also discussed. [ABSTRACT FROM AUTHOR]

The pandemic situation caused by coronavirus clearly demonstrated the need for alternatives able to protect the respiratory tract and inactivate the infectious agents. Based on this, antibacterial face-mask filters of polycaprolactone (PCL) dopped with magnesium oxide (MgO) and copper oxide (CuO) nanoparticles (NPs) were produced using an electrospinning technique. A morphological analysis of electrospun meshes evaluated the success of nanoparticles' incorporation as well as the average fibers' diameters (481 ± 272 nm). The performance of electrospun nanofibers was also assessed in terms of tensile strength (0.88 ± 0.25 MPa), water vapor permeability (11,178.66 ± 35.78 g·m−2·day−1), stability under wet conditions and antibacterial activity according to the standard guidelines. The filters showed structural stability up to 2 h of washing and improved antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) for optimized concentrations of MgO and CuO NPs. Overall, electrospun meshes with antibacterial activity were successfully developed for advanced filtering applications. [ABSTRACT FROM AUTHOR]

Although immune checkpoint inhibitors (ICI) have revolutionized cancer management, patient response can be heterogeneous, and the development of ICI resistance is increasingly reported. Novel treatment strategies are necessary not only to expand the use of ICI to previously unresponsive tumor types but also to overcome resistance. Targeted radionuclide therapy may synergize well with ICIs since it can promote a pro-inflammatory tumor microenvironment. We investigated the use of a granzyme B targeted peptide (GZP) as a cancer theranostic agent, radiolabeled with 68Ga (68Ga-GZP) as a PET imaging agent and radiolabeled with 90Y (90Y-GZP) as a targeted radionuclide therapy agent for combinational therapy with ICI in murine models of colon cancer. Our results demonstrate that GZP increasingly accumulates in tumor tissue after ICI and that the combination of ICI with 90Y-GZP promotes a dose-dependent response, achieving curative response in some settings and increased overall survival. [ABSTRACT FROM AUTHOR]

The present study aims to verify the compatibility of the Marrakesh Treaty for the Visually Impaired – and its limitations imposed on copyright – with the Brazilian legal system, through a systemic analysis that combines international law with domestic law. The reasoning of the work is deductive, starting from the general (international) to the specific (Brazil), its nature is theoretical and reflective, and the methodology used was the search of specialized bibliography and the analysis of normative instruments. The theoretical framework of the research starts from the premise of the existence and validity of International Law, inserted in the context of globalization and applied to the reality of national legal systems, in the light of human rights. The results obtained point to the complete compatibility of the Marrakesh Treaty with the Brazilian legal order, especially for its internalization with force of Constitutional Amendment. [ABSTRACT FROM AUTHOR]

Apramycin and florfenicol are two antimicrobial agents exclusively used in veterinary medicine. Resistance determinants to these antimicrobial agents have been described in several staphylococci, yet no inhibition zone-based epidemiological cutoff (ECOFF) values are available to detect populations harboring resistance mechanisms. In this study, we propose disk diffusion inhibition zone ECOFF values of Staphylococcus aureus for apramycin and florfenicol. The susceptibility to apramycin and florfenicol was evaluated by disk diffusion of five S. aureus collections, comprising 352 isolates of animal (n = 265) and human (n = 87) origin. The aggregated distributions of inhibition zone diameters were analyzed by the normalized resistance interpretation method to obtain normalized wild-type (WT) population distributions and corresponding ECOFF values. The putative WT populations of S. aureus were characterized by an inhibition zone ≥15 mm (ECOFF = 15 mm) for apramycin and ≥21 mm for florfenicol (ECOFF = 21 mm). Five nonwild-type (NWT) isolates were detected for apramycin, all without inhibition zone and harboring the apmA gene, whereas five NWT isolates were identified for florfenicol, all carrying the fexA gene. The proposed ECOFF values for apramycin and florfenicol may be a valuable tool in future antimicrobial resistance monitoring and surveillance studies to identify S. aureus NWT populations toward these antimicrobial agents. [ABSTRACT FROM AUTHOR]

Background: University entry can lead to changes in students' lifestyles making them vulnerable to various health risk factors. Objective: To draw the epidemiological profile regarding lifestyle habits, such as diet, physical activity, lipid profile and stress, in health university students. Materials and Methods: Prospective, cross-sectional, prospective study conducted on students aged 18 to 30 years. The instruments used for the analysis were 24-hour recall, Bouchard recall, complete lipidogram and basal cortisol. Results: We observed high rates of overweight/obesity, increased total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL-c) levels and decreased high density lipoprotein (HDLc) levels. Analysis of the level of physical activity revealed that 58.33% of college students are inactive and 16.66% have high basal cortisol. The body mass index was high, as was the lipid profile with increased TC, LDLc and TG and decreased HDL-c. Conclusion: These results are worrisome because, despite having more access to information, the life habits of health university students are strongly associated with the development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Parque Nacional do Caparaó is located in the Serra do Caparaó in the southeastern region of Brazil. It lies on the border between the states of Espírito Santo and Minas Gerais. It is a large fragment of Atlantic Forest vegetation, with altitudinal variation from 630 to 2,892 m. We present an annotated list of bird species found in the park based on data collected from 2012 to 2018. We recorded 216 species, including 66 endemic, 22 threatened, and 17 newly recorded species. To complete the list of species, we added data available in several bibliographic sources and digital databases, bringing the total number of bird species in the park to 348 and including 98 endemic and 33 threatened species. This work is the first to present an updated list of birds for the park, and the data presented show the importance of this protected area for conservation of birds in the region. [ABSTRACT FROM AUTHOR]

• Host AMPK, mTOR and HIF-1α are key regulators of Leishmania infection. • Leishmania hijacks amino acid metabolism to proliferate inside the host. • Modulation of host metabolism represents an attractive target for leishmaniasis. Manipulation of host metabolic fluxes by Leishmania represents a strategy to circumvent host immune response leading to long-term parasite survival and playing an important role in the pathology of infection. Specific Leishmania -dependent metabolic alterations in infected macrophages have been associated with resistance or susceptibility to infection. Thus, deciphering the multilevel interactions between metabolism and function on innate immune cells during infection offers considerable therapeutic or prophylactic promise. In this review, we provide an overview of recent literature highlighting Leishmania- macrophage interactions and discuss the potential of metabolic targeted therapies to shift the balance of dysfunctional, damaging, or non-productive responses to protective immune reactivity patterns towards pathogen elimination. [ABSTRACT FROM AUTHOR]

This paper aims to develop relationships between the concept of classic, as postulated by the historical-critical pedagogy and the constitution of universal values. In order to achieve this end, the text was divided into three moments. In a first moment we approach the contrast between the conception of knowledge present in the historical-critical pedagogy and the hegemonic conception of knowledge. Secondly, based on the works of Karl Marx (1818-1883) and Friedrich Engels (1820-1895), in productions by György Lukács (1885-1971) and authors with similar thoughts, such as Agnes Heller (1929-2019) and György Márkus (1934-2016), we seek to establish the relationship between the construction of universal values and the classic. And, finally, in a third moment, we analyze the educational work as a process located within the scope of school education and that is linked to the preservation of universal values condensed in the classical knowledge. We concluded that the understanding of the classic from the constitution of universal values is fundamental do understand its confirmation as a product of human activity. The condensed values in classical knowledge, beyond their sociohistorical roots, transcend towards universality. The proper understanding of this process allow us to overcome the antinomy between dogmatism and relativism, a fundamental condition for understanding the concept of classic as postulated by the historical-critical pedagogy. [ABSTRACT FROM AUTHOR]

A previous study showed that N -acetylcysteine (NAC), used after in-vitro exposure to the gonadotoxic chemotherapeutic drug etoposide, has the ability to decrease DNA damage in human spermatozoa; however, it showed no benefit when used before exposure. This study aimed to evaluate the impact of the NAC on the preservation of sperm quality during in-vitro exposure to etoposide. Twenty semen samples were submitted to four experimental conditions: control, NAC-only incubation, etoposide-only incubation, and concomitant etoposide and NAC incubation. After in-vitro incubation, semen parameters, sperm chromatin condensation, sperm DNA fragmentation, sperm oxidative stress and sperm metabolism were used to evaluate the role of NAC in protecting human spermatozoa from etoposide. Etoposide did not affect semen parameters, nor did it cause sperm oxidative damage or alterations in glycolytic profile. However, it induced chromatin decondensation and DNA fragmentation, which were fully prevented by NAC. NAC was able to protect sperm DNA integrity during etoposide treatment in vitro , suggesting that NAC may be useful as an adjuvant agent in preserving male fertility during chemotherapy treatments. [ABSTRACT FROM AUTHOR]

The main purpose of this paper is to analyze the variations in the credibility of the Brazilian monetary policy between the years of 2011 and 2018, highlighting the shifts in the presidency of the Central Bank of Brazil. This main purpose can be divided into other two: i) measuring the credibility of the Brazilian monetary policy between the years of 2011 and 2018; ii) analyzing whether the theory proposed by Rogoff (1985) could be applied to the Brazil during this period. Rogoff's theory states that appointing a "conservative" to head the Central Bank tends to increase the monetary policy credibility. The results shows a great deal of variability of the credibility index, along with more stability during Goldfajn's term in opposite to Tombini's. The article concludes that Rogoff's hypothesis should only be considered as true after analyzing the whole picture, since conjunctural factors would greatly interfere in the index variations. [ABSTRACT FROM AUTHOR]

Background: The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown. Methods: We performed transcriptomics in uninfected and L. donovani-infected macrophages 6 hours post-infection. Glutamine quantification by HPLC was assessed in the supernatant of macrophages throughout the infection course. For experimental L. donovani infections, mice were infected with 1.0 x 108 stationary L. donovani promastigotes. Glutaminase (GLS) chemical inhibition was performed using BPTES and glutamine was administered throughout infection. For combined therapy experiment, a daily administration of miltefosine and glutamine was performed by oral gavage. Parasite burden was determined using a Taqman-based assay. Immune cell phenotyping and cytotoxicity were performed in splenic cells using flow cytometry. Findings: We show that glutamine is essential for the control of L. donovani infection. Transcriptomic analysis of L. donovani-infected macrophages demonstrated an upregulation of genes involved in glutamine metabolism. Pharmacological inhibition of glutaminolysis significantly increased the susceptibility to infection, accompanied by an increased recruitment of anti-inflammatory myeloid cells and impaired T cell responses. Remarkably, the supplementation of glutamine to mice infected with L. donovani during miltefosine treatment potentiates parasite clearance through the development of a more effective anti-Leishmania adaptive immune response. Conclusions: Our data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis. Author summary: Visceral leishmaniasis is a life threatening neglected tropical disease affecting around 500,000 and killing 50,000 individuals a year. Despite its obligatory dependence on host cell metabolism and the lack of effective, non-toxic, orally bioavailable anti-leishmanial drugs, Leishmania-perturbed host cell metabolomes and its relation to anti-leishmanial chemotherapy remains unexplored. Transcriptomic analysis performed on L. donovani-infected macrophages identified patterns of gene expression associated with glutamine metabolism. In vitro and in vivo pharmacological inhibition of glutaminase (GLS), which catalyzes the first reaction in the primary pathway for the catabolism of glutamine, significantly increased the susceptibility to infection demonstrating the role of glutamine metabolism to L. donovani infection. More importantly, we demonstrated that glutamine supplementation during miltefosine treatment potentiates L. donovani clearance through the development of a more effective anti-Leishmania innate and adaptive immune response. Overall, our work demonstrated that glutamine-miltefosine synergy is a novel combined host- and pathogen-directed treatment for combating visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

Radio‐nanomedicine, or the use of radiolabeled nanoparticles in nuclear medicine, has attracted much attention in the last few decades. Since the discovery of Cerenkov radiation and its employment in Cerenkov luminescence imaging, the combination of nanomaterials and Cerenkov radiation emitters has been revolutionizing the way nanomaterials are perceived in the field: from simple inert carriers of radioactivity to activatable nanomaterials for both diagnostic and therapeutic applications. Herein, we provide a comprehensive review on the types of nanomaterials that have been used to interact with Cerenkov radiation and the gamma and beta scintillation of radionuclides, as well as on their biological applications. [ABSTRACT FROM AUTHOR]

Die Radionanomedizin – der Einsatz radiomarkierter Nanopartikel in der Nuklearmedizin – hat in den vergangenen Jahrzehnten immer mehr Aufmerksamkeit gefunden. Seit der Entdeckung der Tscherenkow‐Strahlung und ihrer Anwendung in der Tscherenkow‐Lumineszenzbildgebung revolutioniert die Kombination von Nanomaterialien mit Tscherenkow‐Strahlungsemittern die Haltung gegenüber Nanomaterialien auf diesem Gebiet: von einfachen inerten Radioaktivitätsträgern bis hin zu aktivierbaren Nanomaterialien für diagnostische und therapeutische Anwendungen. Hier werden wir einen umfassenden Überblick über die Nanomaterialtypen, die für die Interaktion mit der Tscherenkow‐Strahlung sowie mit der Gamma‐ und Beta‐Szintillation der Radionuklide eingesetzt wurden, sowie ihre biologischen Anwendungen geben. [ABSTRACT FROM AUTHOR]

• Brackets were adhered to enamel with new antibacterial orthodontic adhesives. • Ionic liquid was used as antibacterial agent for the first time in a dental resin. • Ionic liquid at 15 wt.% showed higher antibacterial property against S. mutans. • The mechanical and bond strength of adhesives were not affected by ionic liquid. • All orthodontic adhesives showed no cytotoxicity against human keratinocytes. The aim of this study was to formulate and evaluate experimental orthodontic adhesives with different concentrations of 1 -n- butyl-3-methylimidazoilium bis(trifluoromethanesulfonyl)imide (BMIM.NTf 2). The experimental orthodontic adhesives were formulated with methacrylate monomers, photoinitiators and silica colloidal. The ionic liquid BMIM.NTf 2 was synthesized and characterized. BMIM.NTf 2 was added at 5 (G 5%), 10 (G 10%) and 15 (G 15%) wt.%. One group contained no BMIM.NTf 2 to function as control (G Ctrl). The adhesives were evaluated for polymerization kinetics, degree of conversion (DC), Knoop hardness and softening in solvent, ultimate tensile strength (UTS), shear bond strength (SBS), thermogravimetric analysis (TGA), antibacterial activity and cytotoxicity. BMI.NTf 2 showed the characteristic chemical peaks. The polymerization kinetics were different among the groups. G 10% and G 15% showed higher DC (p < 0.05). G 5% and G Ctrl had no differences for softening in solvent (p > 0.05). There were no differences for UTS (p > 0.05) and SBS (p > 0.05). TGA showed one different peak for G 15%. All groups with BMIM.NTf 2 showed antibacterial activity compared to G Ctrl (p < 0.05) without cytotoxicity (p > 0.05). To reduce biofilm formation around brackets and to prevent demineralization at susceptible sites, materials have been developed with antibacterial properties. In this study, a new experimental orthodontic adhesive was formulated with an imidazolium ionic liquid (BMIM.NTf 2) as antibacterial agent. The incorporation of 5 wt.% of ionic liquid decreased biofilm formation without affecting the physico-chemical properties and cytotoxicity of an experimental orthodontic resin. [ABSTRACT FROM AUTHOR]

Objectives: To examine the subarachnoid space diameters in chromosomally abnormal fetuses at 11-13 weeks' gestation. Methods: Stored three-dimensional (3D) ultrasound volumes of the fetal head at 11-13 weeks' gestation from 407 euploid and 88 chromosomally abnormal fetuses (trisomy 21, n = 40; trisomy 18, n = 19; trisomy 13, n = 7; triploidy, n = 14; Turner syndrome, n = 8) were analyzed. The subarachnoid space diameters, measured in the sagittal and transverse planes of the fetal head, in relation to biparietal diameter (BPD) in each group of aneuploidies was compared to that in euploid fetuses. A total of 20 head volumes were randomly selected and all the measurements were recorded by two different observers to examine the interobserver variability in measurements. Results: In euploid fetuses, the anteroposterior, transverse and sagittal diameters of the subarachnoid space increased with BPD. The median of the observed to expected diameters for BPD were significantly increased in triploidy and trisomy 13 but were not significantly altered in trisomies 21 and 18 or Turner syndrome. In triploidy, the subarachnoid space diameters for BPD were above the 95th centile of euploid fetuses in 92.9% (13 of 14) cases. The intraclass reliability or agreement was excellent for all three subarachnoid space diameters. Conclusion: Most fetuses with triploidy at 11-13 weeks' gestation demonstrate increased subarachnoid space diameters. [ABSTRACT FROM AUTHOR]

Objectives: To examine the subarachnoid space diameters in chromosomally abnormal fetuses at 11-13 weeks' gestation.Methods: Stored three-dimensional (3D) ultrasound volumes of the fetal head at 11-13 weeks' gestation from 407 euploid and 88 chromosomally abnormal fetuses (trisomy 21, n = 40; trisomy 18, n = 19; trisomy 13, n = 7; triploidy, n = 14; Turner syndrome, n = 8) were analyzed. The subarachnoid space diameters, measured in the sagittal and transverse planes of the fetal head, in relation to biparietal diameter (BPD) in each group of aneuploidies was compared to that in euploid fetuses. A total of 20 head volumes were randomly selected and all the measurements were recorded by two different observers to examine the interobserver variability in measurements.Results: In euploid fetuses, the anteroposterior, transverse and sagittal diameters of the subarachnoid space increased with BPD. The median of the observed to expected diameters for BPD were significantly increased in triploidy and trisomy 13 but were not significantly altered in trisomies 21 and 18 or Turner syndrome. In triploidy, the subarachnoid space diameters for BPD were above the 95th centile of euploid fetuses in 92.9% (13 of 14) cases. The intraclass reliability or agreement was excellent for all three subarachnoid space diameters.Conclusion: Most fetuses with triploidy at 11-13 weeks' gestation demonstrate increased subarachnoid space diameters. [ABSTRACT FROM AUTHOR]

Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging. Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region). Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop. Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env. Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies. In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env. While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region. Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions. [ABSTRACT FROM AUTHOR]

Highlights • High levels of IL-10 in the establishment of infection leads to VL susceptibility. • IL-10 induced susceptibility associates with decreased multifunctional CD4 T cells. • VL susceptibility associates with decreased IFN-γ/IL-10 ratio. Abstract Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility. In this work, we took advantage of a transgenic mouse model that expresses high levels of IL-10 upon zinc sulfate administration (pMT-10). We addressed the role of IL-10 during the initial stages of L. donovani infection by analyzing the parasite burden in the spleen and liver of the infected pMT-10 and WT mice as well as the histopathological alterations upon IL-10 induction. Furthermore, the profile of cytokines expressed by T cells was assessed. Our results demonstrate that an increase in IL-10 production has an impact early but not later after infection. This specific temporal role for IL-10-mediated susceptibility to VL is of interest. [ABSTRACT FROM AUTHOR]

Despite advances in the development of new therapeutic agents and diagnostic imaging techniques, the 5-year survival of osteosarcoma, the most common type of bone cancer, remains practically unaltered for the last three decades at around 60%. Nanoparticle-based carriers have emerged as new class of drug delivery systems that could potentially overcome conventional chemotherapy limitations, by promoting a better drug biodistribution profile by allowing a preferential accumulation of the drug in the desired tissue, while minimising non-targeted tissue toxicity, thus resulting in an improved overall therapeutic effectiveness. Hydroxyapatite nanoparticles (HANP) are known to be biocompatible and non-immunogenic and have shown to be preferentially accumulated in bone tissues being considered a promising carrier to bone tissues. Herein, we successfully synthesised mesoporous hydroxyapatite nanoparticles with mean size of 285.32 ± 10.29 nm and superficial area of 103.5 m2/g, containing significant quantities of chemotherapeutic drug vincristine. A spectrophotometric method was developed and validated aiming to quantify the vincristine (VCR)-loaded in nanoparticles. Chorioallantoic membrane assay revealed relevant anti-angiogenic activity of system, leading to accentuated reduction in the number of blood vessels in fertilised eggs. Findings presented in this paper suggested that VCR-loaded HANP has a promising future as a nanocarrier for bone cancer treatment. [ABSTRACT FROM AUTHOR]

Natural forming clay halloysite is an emerging nanomaterial carrier for sustained drug delivery. These 50 nm diameter aluminosilicate tubes, with inner - alumina and outer - silica surface layers, can be loaded with 10–30 wt% of drug molecules, DNA and enzymes. The opposite charge of the inner and outer halloysite surface allow for selective drug adsorption inside or outside the clay nanotubes. The drug loaded halloysite enhanced the zeta potential of minus 50–60 mV allowing for stable aqueous nanocolloids. Halloysite nanoformulations provide an extended 10–20 h release profile, and may be functionalized (e.g., clogging tubes' end with polymers extending release time to 1–2 weeks or allowing for triggered release), which renders these clay nanostructures as promising controlled delivery systems. Recent studies demonstrate the potential of abundantly available halloysite clay nanotubes for life science applications, from drug delivery via oral or topical administration, to tissue scaffolds and regenerative medicine, while assessing their cellular internalization, stability, biosafety and biocompatibility are featured. The benefits and limitations of halloysite clay nanotubes are discussed, as well as the directions for future developments. [ABSTRACT FROM AUTHOR]

Characterized the scientific literature on mortality atmospheric lightning and reported to the trends observed at these publications. Integrative literature review, with data collection in the Medical Literature Analysis and Retrieval System Online and Atmospheric Electricity Group. Analyzed the period from 1994 to 2014, using the keywords: lightning Injuries, mortality and nursing. The sample consists of 13 articles, 69.2% published in English and 30.8% in Portuguese. Most of the studies were published in the 2000s, corresponding to 92.3% of raised research. Accidents by lightning are responsible for 0.3 to 6 deaths/million persons/year in developed and developing countries, respectively. Most of the victims were young assets reached during outdoor activities. Such accidents have serious consequences, such as physical damage, unconsciousness or death. The results identified the lack of publications, as well as the occurrence of entirely preventable accidents. It was concluded that nursing should act in health education in order to avoid occurrence of deaths from lack of information. [ABSTRACT FROM AUTHOR]

Despite recent advances in the development of new therapeutic agents and diagnostic imaging modalities, cancer is still one of the main causes of death worldwide. A better understanding of the molecular signature of cancer has promoted the development of a new generation of anti-cancer drugs and diagnostic agents that specifically target molecular components such as genes, ligands, receptors and signaling pathways. However, intrinsic heterogeneity of tumors has hampered the overall success of target therapies even among patients with similar tumor types but unpredictable different responses to therapy. In this sense, post-treatment response monitoring becomes indispensable and nuclear medicine imaging modalities could provide the tools for an early indication of therapeutic efficacy. Herein, we briefly discuss the current role of PET and SPECT imaging in monitoring cancer therapy together with an update on the current radiolabeled probes that are currently investigated for tumor therapy response assessment. [ABSTRACT FROM AUTHOR]

As reported in our previous work, the association of nanofiltration (NF) and reverse osmosis (RO) has proved to be a promising treatment for pressure oxidation process (POX) effluent, generated in gold ore processing. Despite the excellent performance achieved, it was essential to evaluate if the membrane performance could be impaired by continuous exposure to effluent. Accordingly, this study aimed to investigate the effect of continuous exposure to POX effluent on characteristics of nanofiltration (MPF-34) and reverse osmosis (TFCHR) membranes, used in POX effluent treatment. The membranes were immersed in the effluent and in acid solutions in order to simulate the continuous exposure during the treatment. The effect of exposure on NF membrane was evaluated based on the rejections of glucose, magnesium sulfate, sulfuric acid, and cobalt and nickel sulfates. The effect of exposure on the RO membrane was evaluated by assay of the rejections of sodium chloride and sulfuric acid. For both membranes, the effects of the exposure on the hydraulic permeability, hydrophobicity, and chemical and morphological characteristics were also evaluated. For MPF-34, the cobalt and nickel rejection decreased by 33% during exposure period, indicating a reduction of the NF ability in separation of metals from acid solution. TFC-HR membrane exhibited satisfactory stability under the acidic conditions employed in this investigation, thus exhibiting potential for practical implementation. [ABSTRACT FROM AUTHOR]

Despite efforts, cancer is still one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths each year, according to the World Health Organization. Among the strategies to reduce cancer progression and improving its management, implementing early detection technologies is crucial. Based on the fact that several types of cancer cells overexpress surface receptors, small molecule ligands, such as peptides, have been developed to allow tumor identification at earlier stages. Allied with imaging techniques such as PET and SPECT, radiolabeled peptides play a pivotal role in nuclear medicine. Bombesin, a peptide of 14 amino acids, is an amphibian homolog to the mammalian gastrin-releasing peptide (GRP), that has been extensively studied as a targeting ligand for diagnosis and therapy of GRP positive tumors, such as breast, pancreas, lungs and prostate cancers. In this context, herein we provide a review of reported bombesin derivatives radiolabeled with a multitude of radioactive isotopes for diagnostic purposes in the preclinical setting. Moreover, since animal models are highly relevant for assessing the potential of clinical translation of this radiopeptides, a brief report of the currently used GRP-positive tumor-bearing animal models is described. [ABSTRACT FROM AUTHOR]

This work assessed the potential of nanofiltration (NF) and reverse osmosis (RO) to treat acid streams contaminated with metals, such as effluent from the pressure oxidation process (POX) used in refractory gold ore processing. NF and RO were evaluated in terms of rejections of sulfuric acid and metals. Regarding NF, high sulfuric acid permeation (~100%), was observed, while metals were retained with high efficiencies (~90%), whereas RO led to high acid rejections (<88%) when conducted in pH values higher than 1. Thus, sequential use of NF and RO was proved to be a promising treatment for sulfuric acid solutions contaminated by metals, such as POX effluent. In this context, a purified acid stream could be recovered in NF permeate, which could be further concentrated in RO. Recovered acid stream could be reused in the gold ore processing or commercialized. A metal-enriched stream could be also recovered in NF retentate and transferred to a subsequent metal recovery stage. In addition, considering the high acid rejection obtained through the proposed system, RO permeate could be used as recycling water. [ABSTRACT FROM AUTHOR]

This article is an outcome of the study, decisions, and restoration work undertaken during the integrated conservation project of the 16th century paintings of Funchal's Cathedral main chapel's altarpiece, in Madeira Island, Portugal. After diagnostic research has allowed a complete understanding of the original material of the 12 Portuguese-Flemish paintings, it has been revealed the presence of other superimposed layers, whether actual overpaints or the accumulation of materials occurring in time over the old ones. Identification together with the cleaning and removal of these coatings was a delicate and a complex process. Conservators already suspected the existence of overpaints in some paintings, a close observation of the painted surface showed differences in terms of color, texture, and execution technique in specific areas. Chemical and stratigraphical research together with radiography and historical research on primary documental sources provided important clues about the paintings of the previous interventions and relevant and crucial information for the decision making. © 2016 Wiley Periodicals, Inc. Col Res Appl, 41, 283-288, 2016 [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether total bacterial count in cervicovaginal fluid is associated with failure of metronidazole therapy for bacterial vaginosis.Methods: In a cross-sectional study, women attending a primary health center in Botucatu, São Paulo, Brazil, for routine cervical screening between September 2012 and October 2013 were enrolled. Women who tested positive for bacterial vaginosis (Nugent classification) were offered oral metronidazole. Women who completed metronidazole treatment and an equal number of control women with normal vaginal flora at initial screening were included in analyses of total bacterial count, assessed by flow cytometry of cervicovaginal fluid samples.Results: Of 287 women who enrolled, 49 were excluded because they tested positive for trichomoniasis, chlamydial endocervicitis, gonorrhea, or candidiasis. Among the remaining 238, 85 (35.7%) had bacterial vaginosis. Among 36 women evaluated at follow-up, 23 (63.9%) had successfully restored lactobacilli-dominant flora, 12 (33.3%) had persistent bacterial vaginosis, and 1 (2.8%) had vaginal candidiasis (excluded from flow cytometry). Total bacterial count did not differ between 35 women with bacterial vaginosis and 35 with normal vaginal flora (P=0.62). Total bacterial count did not differ at enrollment between women who went on to have persistent bacterial vaginosis and those who had successful treatment (P=0.78).Conclusion: Failure of oral metronidazole therapy for bacterial vaginosis was not associated with total bacterial count in cervicovaginal fluid. [ABSTRACT FROM AUTHOR]

This work assessed the viability of implementing sequential stages of microfiltration (MF), nanofiltration (NF) and reverse osmosis (RO) to recover sulfuric acid, separate noble metals, and produce high quality reuse water from a gold mining effluent, specifically from a pressure-oxidation process effluent. Additionally, lime demand for neutralization of the proposed treatment streams and current lime demand were compared. It was observed that the NF attained high sulfuric acid permeation, equivalent to 82%, and a substantial acid purification of approximately 77% in relation to feed solution. Moreover, the RO increased the acid content by 99% in relation to feed solution considering a recovery rate of 50%. The final RO permeate had low conductivity and reduced content of total solids and contaminants, thus showing promising potential for industrial reuse. Furthermore, the acid recovery did not led to an important loss of metals of high commercial value which were present in the raw effluent since their retention in the concentrates of the MF and NF was above 95%. The neutralization of the MF and NF concentrates allowed for a 20% reduction in lime consumption in relation current demand. [ABSTRACT FROM AUTHOR]

Identity fusion involves a visceral feeling of oneness with a group, despite personal and social selves remaining differentiated. Previous research on identity fusion has focused on samples of adults and adolescents. The present studies aim at exploring how and when identity fusion develops in childhood. Our first goal was to find out to what extent personal and social identities must be developed for fusion to become possible. We conducted two exploratory studies where school-age children (six to 12 years old) participated in either focus group sessions or individual interviews. Our results show that although children are able to feel strongly connected with a group and express willingness to make significant personal sacrifices for the group, they fail to show fusion as it is found in adults, since their personal identity is not fully developed yet. Instead, these findings suggest the existence of a prior feeling that we called ‘protofusion’, the core of which is the strength of the relational ties with the members of the group. [ABSTRACT FROM AUTHOR]

Little is known about the stability of HIV-1 cross-neutralizing responses. Taking into account the fact that neutralization breadth has been positively associated with plasma viral load, there is no explanation for the presence of broadly neutralizing responses in a group of patients on treatment with undetectable viremia. In addition, the B-cell profile responsible for broadly cross-neutralizing responses is unknown. Here we studied the evolution of neutralizing responses and the B-cell subpopulation distribution in a group of patients with broadly cross-reactive HIV-1-neutralizing activity. We studied neutralization breadth evolution in a group of six previously identified broadly cross-neutralizing patients and six control patients during a 6-year period with a previously described minipanel of recombinant viruses from five different subtypes. B-cell subpopulation distribution during the study was also determined by multiparametric flow cytometry. Broadly cross-neutralizing activity was transient in four broad cross-neutralizers and stable, up to 4.6 years, in the other two. In four out of five broad cross-neutralizers who initiated treatment, a neutralization breadth loss occurred after viremia had been suppressed for as much as 20 months. B-cell subpopulation analyses revealed a significant increase in the frequency of naive B cells in broadly cross-reactive samples, compared with samples with less neutralization breadth (increased from 44% to 62%). We also observed a significant decrease in tissue-like and activated memory B cells (decreased from 19% to 12% and from 17% to 9%, respectively). Our data suggest that HIV-1 broadly cross-neutralizing activity is variable over time and associated with detectable viremia and partial B-cell restoration. [ABSTRACT FROM AUTHOR]

Little is known about the stability of HIV-1 cross-neutralizing responses. Taking into account the fact that neutralization breadth has been positively associated with plasma viral load, there is no explanation for the presence of broadly neutralizing responses in a group of patients on treatment with undetectable viremia. In addition, the B-cell profile responsible for broadly cross-neutralizing responses is unknown. Here we studied the evolution of neutralizing responses and the B-cell subpopulation distribution in a group of patients with broadly cross-reactive HIV-1-neutralizing activity. We studied neutralization breadth evolution in a group of six previously identified broadly cross-neutralizing patients and six control patients during a 6-year period with a previously described minipanel of recombinant viruses from five different subtypes. B-cell subpopulation distribution during the study was also determined by multiparametric flow cytometry. Broadly cross-neutralizing activity was transient in four broad cross-neutralizers and stable, up to 4.6 years, in the other two. In four out of five broad cross-neutralizers who initiated treatment, a neutralization breadth loss occurred after viremia had been suppressed for as much as 20 months. B-cell subpopulation analyses revealed a significant increase in the frequency of naive B cells in broadly cross-reactive samples, compared with samples with less neutralization breadth (increased from 44% to 62%). We also observed a significant decrease in tissue-like and activated memory B cells (decreased from 19% to 12% and from 17% to 9%, respectively). Our data suggest that HIV-1 broadly cross-neutralizing activity is variable over time and associated with detectable viremia and partial B-cell restoration. [ABSTRACT FROM AUTHOR]

The earthworm Eisenia foetida (Annelida, Oligochaeta) is an excellent biosentinel model organism for assessing potential toxicological risks by xenobiotics in terrestrial ecosystems. Methamidophos is an organophosphorous insecticide widely used to control agricultural pests. Its main action is due to inhibition of the enzyme acetylcholinesterase. The aim of this study was to evaluate the toxicity of methamidophos on the morphology and male parameters in Eisenia foetida. After determining the LD50 for methamidophos (85.34 mg/kg soil), five groups were formed, including control subjects, and sprayed with tap water. Methamidophos treated groups were subjected to doses of 1/10, 1/6, 1/3 and 2/3 of the LD50. Each group was analyzed at day 1, 6, 14 and 30 post-treatment. The results show a significant decrease in the weight of all individuals treated with methamidophos, besides showing a coiled body in 100% of them. Sperm count showed a significant increase in the treated groups after 1, 6 and 14 days post exposure and a significant decrease by day 30. Using the technique of acridine orange, a significant increase in abnormal metachromatic sperm (red fluorescence) in treated animals was shown. Methamidophos alters the overall behavior in earthworms and the male reproductive parameters of Eisenia foetida possibly altering the structure and conformation of DNA. [ABSTRACT FROM AUTHOR]

The similarities of electrospun fibers with the skin extracellular matrix (ECM) make them promising structures for advanced wound dressings. Moreover, infection and resistance in wounds are a major health concern that may be reduced with antibacterial wound dressings. In this work, a multifunctional wound dressing was developed based on gelatin/chitosan hybrid fibers dopped with phlorotannin-enrich extract from the seaweed Undaria pinnatifida. The intrinsic electrospun structure properties combined with the antimicrobial and anti-inflammatory properties of phlorotannin-enrich extract will enhance the wound healing process. Electrospun meshes were produced by incorporating 1 or 2 wt% of extract, and the structure without extract was used as a control. Physico-chemical, mechanical, and biological properties were evaluated for all conditions. Results demonstrated that all developed samples presented a homogenous fiber deposition with the average diameters closer to the native ECM fibrils, and high porosities (~90%) that will be crucial to control the wound moist environment. According to the tensile test assays, the incorporation of phlorotannin-enriched extract enhances the elastic performance of the samples. Additionally, the extract incorporation made the structure stable over time since its in vitro degradation rates decreased under enzymatic medium. Extract release profile demonstrated a longstanding delivery (up to 160 days), reaching a maximum value of ~98% over time. Moreover, the preliminary antimicrobial results confirm the mesh's antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. In terms of biological characterization, no condition presented cytotoxicity effects on hDNF cells, allowing their adhesion and proliferation over 14 days, except the condition of 2 wt% after 7 days. Overall, the electrospun structure comprising phlorotannins-enriched extract is a promising bioactive structure with potential to be used as a drug delivery system for skin regeneration by reducing the bacterial infection in the wound bed. [ABSTRACT FROM AUTHOR]

In recent decades, several epimers of peptides containing d -amino acids have been identified in antimicrobial sequences, a feature which has been associated with post-translational modification. Generally, d -isomers present similar or inferior antimicrobial activity, only surpassing their epimers in resistance to peptidases. The naturally occurring l -Phenylseptin (l -Phes) and d -Phenylseptin (d -Phes) peptides (FFFDTLKNLAGKVIGALT- nh 2) were reported with d -epimer showing higher activity against Staphylococcus aureus and Xanthomonas axonopodis in comparison with the l -epimer. In this study, we combine structural (CD, solution NMR), orientational (solid-state NMR) and biophysical (ITC, DSC and DLS) studies to understand the role of the d -phenylalanine in the increase of the antimicrobial activity. Although both peptides are structurally similar in the helical region ranging from D4 to the C-terminus, significant structural differences were observed near the peptides' N-termini (which encompasses the FFF motif). Specific aromatic interactions involving the phenylalanine side chains of d -Phes is responsible to maintaining the F1-F3 residues on the hydrophobic face of the peptide, increasing its amphipathicity when compared to the l -epimer. The higher capability of d -Phes to exert an efficient anchoring in the hydrophobic core of the phospholipid bilayer indicates a pivotal role of the N-terminus in enhancing the interaction between the d -peptide and the membrane interface in relation to its epimer. [Display omitted] • Structural and biophysical investigations of the L and D-phenylseptins reveal details of the peptide-membrane interactions. • The role of the D-phenylalanine in the increase of the antimicrobial activity. • Interactions of phenylalanine side chains of D-phenylseptin strengthen the peptide amphipathicity and its membrane affinity. [ABSTRACT FROM AUTHOR]

Objectives.to examine the Food and Nutrition Surveillance System (Sisvan) as a tool for monitoring the National Strategy for Healthy Complementary Nutrition (ENPACS) in the 40 municipalities overseen by the Belo Horizonte regional superintendent for health (SRS-BH). Methods: a descriptive study was carried out involving all children aged under two being accompanied by the Sisvan Web between 2008 and 2011. The coverage of the Sisvan Web was calculated by dividing the number of children aged under two years accompanied by the Sisvan Web by the total population for the same age group. A questionnaire relating to the technical references of the Sisvan of the municipalities under investigation was sent to collect information on the functioning of the Sisvan. Results: the coverage of the Sisvan Web, in all municipalities, varied from 4.3% (2008) to 10.7% (2011). The questionnaire was answered by 38 municipalities in the SRS-BH, 31.6% of whom reported using data from the Sisvan Web system as a basis for nutritional interventions. Conclusions: the study identified low coverage, poor utilization of data and the need to improve the Sisvan, in order to generate consistent information on nutrition and food among children aged under two years, thereby making it appropriate for monitoring of the ENPACS. [ABSTRACT FROM AUTHOR]

Among the theories that attempt to explain the elevational distribution of metazoan species along elevational gradients, the Mid-Domain Effect (MDE) is one of most debated and criticized. Here, we test whether the diversity of birds along elevational gradients in the Serra do Caparaó, a mountain of the Brazilian Atlantic Forest, is explicable by the MDE. We sampled an elevational gradient between 970 m.a.s.l. and 1970 m.a.s.l. of forest vegetation, with elevational bands every 100 m. We observed a hump-shaped richness pattern of birds along the gradient, with more species in intermediate elevations. It decreased at lower and higher elevations, thereby following a unimodal distribution. Distribution of species richness indicated a high correlation with the tested MDE null model. The result was the same for endemic species. Considering the total bird species registered, up to 30% are endemic and 9 are endangered. Threatened species richness followed a different elevational distribution along the gradient: three species occurred at the lower elevations, two at the interquartile elevations and four at the highest elevations. Despite finding more species in the intermediate elevations, the areas of low and high elevations are also important for the maintenance of endemic and threatened species. To test the MDE theory and compare our results with other studies, we highlight the importance of standardized samplings and habitats. Moreover, we focus on the characterization of the surrounding landscape, which can also influence the richness of bird species diversity. • Medium domain effect (MDE) is an explanation for the unimodal distribution pattern of species diversity in the mountains. • We tested whether the MDE explains the distribution of bird species richness in a mountain area in the Atlantic Forest. • The distribution of bird species richness indicated a high correlation with the null model of tested MDE. • The characterization of the surrounding landscape can influence the pattern of distribution of the bird species. [ABSTRACT FROM AUTHOR]

Brown seaweeds are recognized sources of compounds with a wide range of properties and applications. Within these compounds, phlorotannins are known to possess several bioactivities (e.g., antioxidant, anti-inflammatory, and antimicrobial) with potential to improve wound healing. To obtain phlorotannins enriched extracts from Undaria pinnatifida, a biorefinery was set using low-cost industry-friendly methodologies, such as sequential solid–liquid extraction and liquid–liquid extraction. The obtained extracts were screened for their antioxidant and antimicrobial activity against five common wound pathogens and for their anti-inflammatory potential. The ethanolic wash fraction (wE100) had the highest antioxidant activity (114.61 ± 10.04 mmol·mg−1 extract by Diphenyl-1-picrylhydrazyl (DPPH) and 6.56 ± 1.13 mM eq. Fe II·mg−1 extract by and Ferric Reducing Antioxidant Power (FRAP)), acting efficiently against Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria, and showing a nitric oxide production inhibition over 47% when used at 0.01 µg·mL−1. NMR and FTIR chemical characterization suggested that phlorotannins are present. Obtained fraction wE100 proved to be a promising candidate for further inclusion as wound healing agents, while the remaining fractions analyzed are potential sources for other biotechnological applications, giving emphasis to a biorefinery and circular economy framework to add value to this seaweed and the industry. [ABSTRACT FROM AUTHOR]

A comprehensive investigation of the Hg2+ coordination chemistry and 197m/gHg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, p-SCN-Bn- DOTA and p-SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the 197m/gHg2+ theranostic pair. Radiolabeling studies revealed that TCMC and DOTA exhibited low radiochemical yields (0%-6%), even when subjected to harsh conditions (80°C) and high ligand concentrations (10-4 M). In contrast, p-SCN-Bn-TCMC and p-SCN-Bn-DOTA demonstrated significantly higher 197m/gHg radiochemical yields (100% ± 0.0% and 70.9% ± 1.1%, respectively) under the same conditions. The [197m/gHg]Hg-p-SCN-Bn-TCMC complex was kinetically inert when challenged against human serum and glutathione. To understand the differences in labeling between the commercial chelators and their bifunctional counterparts, non-radioactive natHg2+ complexes were assessed using NMR spectroscopy and DFT calculations. The NMR spectra of Hg- TCMC and Hg-p-SCN-Bn-TCMC suggested binding of the Hg2+ ion through the cyclen backbone framework. DFT studies indicated that binding of the Hg2+ ion within the backbone forms a thermodynamically stable product. However, competition can form between isothiocyanate binding and binding through the macrocycle, which was experimentally observed. The isothiocyanate bound coordination product was dominant at the radiochemical scale as, in comparison, the macrocycle bound product was seen at the NMR scale, agreeing with the DFT result. Furthermore, a bioconjugate of TCMC (TCMC- PSMA) targeting prostate-specific membrane antigen was synthesized and radiolabeled, resulting in an apparent molar activity of 0.089 MBq/nmol. However, the complex demonstrated significant degradation over 24 h when exposed to human serum and glutathione. Subsequently, cell binding assays were conducted, revealing a K, value ranging from 19.0 to 19.6 nM. This research provides crucial insight into the effectiveness of current commercial chelators in the context of 197m/gHg2+ radiolabeling. It underscores the necessity for the development of specific and customized chelators to these unique "soft" radiometals to advance 197m/gHg2+ radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Orthodontic adhesives with antimicrobial and remineralizing properties may be an alternative to control white spot lesions around brackets. The aim of this study is to develop an experimental orthodontic adhesive containing boron nitride nanotubes (BNNT) and alkyl trimethyl ammonium bromide (ATAB). Methacrylate (BisGMA and TEGDMA) monomers were used to formulate the adhesives. Four experimental groups were produced with the addition of 0.1 wt.% BNNT (GBNNT); 0.1 wt.% ATAB (GATAB); and 0.2 wt.% BNNT with ATAB (GBNNT/ATAB); in the control group, no fillers were added (GCtrl). The degree of conversion, cytotoxicity, softening in solvent, contact angle and free surface energy, antibacterial activity, shear bond strength, and mineral deposition were evaluated. Adhesives achieved degree of conversion higher than 50% and cell viability higher than 90%. GBNNT and GATAB adhesives exhibited reduced softening in solvent. Mean free surface energy was decreased in the GBNNT adhesive. Significant reduction in bacterial growth was observed in the GBNNT/ATAB. No statistical difference was found for shear bond strength. Mineral deposition was found in GBNNT, GATAB, and GBNNT/ATAB groups after 14 and 28 days. The addition of 0.2% BNNT/ATAB to an experimental orthodontic adhesive inhibited bacterial growth and induced mineral deposition without affecting the properties of the material. [ABSTRACT FROM AUTHOR]

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first‐line anti‐leishmanial drugs. Despite being pro‐inflammatory, the in vitro generated uninfected lipid‐laden macrophages (LLMs) or adipose‐tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL‐10 and lower IL‐12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti‐leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high‐fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+CD11b+CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first‐line anti‐leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host‐protective immune response and reducing the efficacy of antiparasitic drug therapies. [ABSTRACT FROM AUTHOR]

The 2030 Agenda for Sustainable Development and the SDGs are currently a central pillar of action for international organizations, determining development and cooperation actions at a global scope. From a technical perspective, to build and systematize information for the alignment and subsequent monitoring of policies and indicators implies a significant effort. Especially at the sub-national level, this collides with small local governments often lacking experience and resources when it comes to monitoring policies, which affects their ability to keep track of their performance towards SDGs. This article presents the adaptation of RIA methodology for SDGs monitoring at a local level. Its empirical application in six departmental governments in Uruguay made it possible to assess their contributions to the fulfillment of the 2030 Agenda and to deepen debates regarding the prerogatives and quality of policies at sub-national levels. [ABSTRACT FROM AUTHOR]

Angiogenesis, the complex process of formation of new blood vessels from pre-existing blood vessels, which involves the participation of several pro- and anti-angiogenic factors, is implicated in many physiological and pathological conditions. Nanoparticle-based anti-angiogenic activity at the tumour tissue, harnessed by the Enhanced Permeability and Retention Effect (EPR effect), could potentially become a breakthrough therapy to halt tumour progression. Herein, we evaluate the anti-angiogenic effect of ZnWO4 nanoparticles (NPs). The nanoparticles were obtained by microwave-assisted hydrothermal synthesis (MAHS) at 120 °C for 60 min and were structurally characterised by X-ray diffraction (XRD) and micro-Raman (MR) spectroscopy. The mean size and polydispersity index were estimated by Zeta potential analysis. The XRD analysis revealed structural organisation at a long-range order, with an average crystallite size of around 3.67 nm, while MR revealed short-range order for ZnWO4. The anti-angiogenic potential of zinc tungstate nanoparticles was investigated through the chorioallantoic membrane assay (CAM) using fertilised chicken eggs. We demonstrate, in an unprecedented way, that nanocrystalline ZnWO4 NPs obtained by MAHS, at low reaction temperatures, showed excellent anti-angiogenic properties even at low concentrations. The ZnWO4 NPs were further evaluated for its cytotoxicity in vitro. [ABSTRACT FROM AUTHOR]

Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for the treatment of solid tumors or hematological malignancies. The polymer carrier and drug pharmacokinetics were independently evaluated to elucidate the relationship between the nanosystem structure and its distribution in the body. Positron emission tomography and optical imaging demonstrated enhanced tumor accumulation of the polymer carriers in 4T1-bearing mice with increased tumor-to-blood and tumor-to-muscle ratios. Additionally, there was a significant accumulation of doxorubicin bound to various polymer carriers in EL4 tumors, as well as excellent in vivo therapeutic activity in EL4 lymphoma and moderate efficacy in 4T1 breast carcinoma. The linear nanomedicine showed at least comparable pharmacologic properties to the star-like nanomedicines regarding doxorubicin transport. Therefore, if multiple parameters are considered such as its optimized structure and simple and reproducible synthesis, this polymer carrier system is the most promising for further preclinical and clinical investigations. [Display omitted] [ABSTRACT FROM AUTHOR]