Mexico shows a high prevalence of obesity in children and adolescents. Geographical location and cultural environment could play a role in the promotion of healthy lifestyles in terms of physical activity (PA), sedentary behavior (SB) and nutrition. The purpose of this study was to assess rural and urban differences in body composition (BC), physical fitness (PF), PA and nutritional status of adolescents from the state of Jalisco (Mexico). The study involved 469 students aged 13-17 years (55.0% girls) from 8 high schools. BC was analyzed by bioimpedance, and PF by standardized field tests. Objective measurements of PA and SB were taken in a subsample (n=240). Energy intake (EI) was calculated from two 24h recalls. Rural residents presented a higher prevalence of overweight, waist circumference, trunk fat mass, regional fat free mass and muscle handgrip strength (all p<0.05, ηp2<0.06). Cardiorespiratory fitness was similar among participants, whereas urban adolescents showed higher muscle power, speed-agility and flexibility scores (all p<0.05, ηp2<0.07). Overall lifestyle behavior in urban adolescents was more sedentary (p<0.05, ηp2= 0.11). EI was similar in both locations. In conclusion, urban Mexican adolescents presented a generally higher sedentary behavior and better fitness and fatness profile than their rural peers.

(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. Yet, several complications were reported, like vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.

Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R) was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1R and AT2R on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1R and 2.97% through 4.57% for AT2R. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, AT1 and AT2 receptors was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1 and AT2 receptors on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1 and 2.97% through 4.57% for AT2. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

Geotechnology techniques were used to specialize the occurrences of the species, based on forest inventories and information available in open-access databases, as well as data from herbaria with catalogs available online, and bibliographical references indicating places of occurrence in the Amazon. GIS-integrated Weighted Mean Ordination (WMO) was chosen as the technique for evaluating the topoclimatic index. Thirteen topoclimatic variables were used, applying principal component analysis techniques such as multidimensional preference to compare the participation of each variable in the two components; Biplot to identify the relationships between the variables and cluster to identify the average distance between proximal classes. The interpolated surfaces of the specialized climatic variables were separated into frequency bands that helped calculate the probability of occurrence, from which a scale of 0 to 10 was established, indicating lower and higher probabilities. Three potential zones were identified, classified as high, medium and low, where areas with high potential occupied 32% of the territory of Pará, medium areas 36% and 32% with low potential for cultivation and presence. The intermediate class had the highest percentage, totaling 36% of the state, explained by the average ratio between the weights adopted.

Micro-nano-plastics (MNPs) are an important constituent of atmospheric aerosol. However, there is still no standard procedure for their sampling and size fractionation, which is an obstacle to the aggregation and critical analysis of results obtained by different research groups. This review focuses on the sampling and fractionation methodologies used for MNPs. Moreover, a straightforward optimized methodology for the sampling and fractionation is proposed.

Peri-implantitis continues to be one of the major reasons for implant failures. We propose a new approach for incorporating MTA into Zirconia implant surfaces with Nd:YAG laser and investigate the biological response of peri-implant cells as well as the microbiological response. Discs of Zirconia stabilized with Yttria and Titanium were produced according 4 tested groups: Nd:YAG laser textured Zirconia coated with MTA (Zr MTA); Nd:YAG laser textured Zirconia (Zr Textured); Zirconia and Titanium discs (Zr and Ti ). Contact profilometry was used to evaluate surface roughness. Human osteoblasts, gingival fibroblasts and S. oralis were cultured on samples. Cell adhesion and morphology, cell viability, cell differentiation markers and bacterial growth were assessed. Zr Textured roughness was significantly higher compared to all other groups. Cellular adhesion was observed at 1 day in all samples in both cell lines. Osteoblasts viability was lower in Zr MTA group, unlike fibroblasts viability was shown to be higher in Zr MTA group compared to Zr Textured group at 3 and 7 days. Osteocalcin and IL-8 release by osteoblasts were higher in Zr MTA. Zr Textured showed higher IL-8 values released by fibroblasts. No differences in S. oralis CFUs were observed between groups. The results suggest that Zirconia implant surfaces coated with MTA seems to promote fibroblasts proliferation and osteoblasts differentiation, however does not appear to have antibacterial properties.

Tabebuia aurea (Silva Manso) Benth. & Hook. f. The ex S.Moore (yellow ipe), belonging to the Bignoniaceae family, used in the popular for fever, inflammation and healing of skin wounds. The extract was prepared by maceration, using 70% ethanol. Through HPLC analysis, it was possible to identify substances, mainly phenolic, such as lapachol, present in Bignoniaceae. The phenolic content was 21.36 mg / Eag in the antioxidant activity, the effective concentration of 50% was 53.03 ± 1.14 µg / mL. The antimicrobial activity against S.aureus, E. coli and C. albicans was evaluated by microdilution in broth, which verified action against the tested microorganisms. Cell viability has been inhibited for tumor cells, although this has not been observed for normal cells. The LD50 against A.aegypti mosquito larvae was 3504.6 mg / L and there was no mortality in the concentration tested for the snail B.glabrata. Nontoxic or low toxicity for A. salina and T. molitor, respectively, and did not exhibit hemolytic action at concentrations of antibacterial effect. Given the above, it was concluded that the bark extract of the studied species has bioprospecting potential for the future development of antimicrobial products.

In the semi-arid region of Brazil, it is common to use saline or brackish water for crop production. However, this practice can negatively affect the soil, nutrient balance, and fruit quality and production. From this perspective, this study aimed to evaluate the effect of fertilization combinations with nitrogen (N), phosphorus (P), and potassium (K) on the production and quality of West Indian cherry grown under salt stress in the second year of production. The study was conducted in a protected environment following a randomized block design with treatments distributed in a 2 x 10 factorial arrangement referring to two levels of electrical conductivity of irrigation water (ECw) (0.6 and 4.0 dS m-1) and 10 NPK fertilization combinations (80-100-100; 100-100-100; 120-100-100; 140-100-100; 100-80-100; 100-120-100; 100-140-100; 100-100-80; 100-100-120 e 100-100-140% of the recommendation in the second year of production), with three replicates and one plant per lysimeter. The results indicate that irrigation of West Indian cherry crop irrigation at the water salinity of 4.0 dS m-1 negatively affected all fruit production variables. The interaction between the ECw of 0.6 dS m-1 and the 100-80-120 NPK fertilization combination increased the total number of fruits and the total fruit weight of West Indian cherry.

Objective: To evaluate the direct costs of treating patients with neuromyelitis optica spectrum disorders (NMOSD) in outpatient care, from a hospital and Unified Health System (SUS) perspective. Methods: Observational study with data collection by microfunding, carried out with patients diagnosed with neuromyelitis optics, treated at a university hospital, in the city of Rio de Janeiro. Mann-Whitney tests were performed to measure cost differences between patient groups by disease severity and analysis perspective. Results: Nine individuals with a median age of 48 years (IQR 30 - 59 years) were included. The median total costs for patients with greater severity from the perspective of the SUS and the hospital were R$ 21,638.22 (IIQ: R$ 15,614.63; R$ 25,985.32) and R$ 32,094.11 (IIQ: R$ 25,610 .60; R$ 38,617.25) respectively. For patients with moderate severity the median was R$ 7,339.85 (IIQ: R$ 6,235.45; R$ 11,912.05) from the SUS perspective and R$ 11,505.80 (IIQ: R$ 7,339.85; R$ 22,424.76) from the perspective of the hospital, where the use of medications had a major impact. Conclusion: The main cost drivers were medicines, especially those used off-label, and procedures.

Background: Homologous Recombination (HR) is the most accurate repair pathway for double-strand breaks and replication fork disruption that is capable of faithfully restoring the original nucleotide sequence of the broken DNA. The deficiency in this mechanism is a frequent event in tumorigenesis. Therapies that exploit defects in HR have been explored essentially in breast, ovarian, pancreas, and prostate cancers, but poorly in colorectal cancers (CRC) although CRC ranks second in mortality worldwide. Methods: Tumor specimens and matched healthy tissues from 63 patients with CRC were assessed for gene expression of HR key components and MMR status, which were correlated with clinicopathological features, progression-free survival, and overall survival (OS). Results: Enhanced expression of MRE11A, the gene encoding a key molecular actor for resection is significantly overexpressed in CRC, is associated with the occurrence of primary tumors particularly T3-T4 and is found in more than 90% of the right-side of CRC, the location with worst prognostic. Importantly, we also found that high MRE11A transcript abundance is associated with 16.7 months shorter OS and a 3.5 higher risk of death. Conclusion: Monitoring MRE11 expression could be used both as a predictor of outcome and as a marker to select CRC patients for treatments thus far adapted for HR deficient cancers.

Abstract: The spectral and dynamic properties of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)

The cannabis plant has been known for millennia for its properties such as textile fiber, food, recreational and medicinal use. Since the origin of its domestication in Asia, cannabis has been transported to the rest of the continents by merchants, nomads, settlers, and slaves, who have also carried with them valuable knowledge about its uses. Its medical use was one of the major contributions of this plant in the various civilizations through which it passed. This article aims to understand its origins, dissemination, and medical use over the years to the present day.

Cryptococcus neoformans is a fungus that mainly affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, part of the first line of defense, important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse" taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal or capsule total did not present toxic effects for the DH82 macrophage cell line. However, it was possible to demonstrate that phagocytic activity was decreased after treatment with polysaccharides. In addition, yeasts recovered from macrophages treated with the polysaccharides, after phagocytosis, could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR- expression. Furthermore, our data suggests that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.

This study compares lifestyles behaviour in Italian and Latvian university students, to assess if there are differences for sex, age, university or studies specialties. An online questionnaire investigating 8 lifestyle dimensions has been compiled by 156 (43,6 % females) from Italy and 105 from Latvia (82,9% females). Answers were collected between April and December 2020. Presence of smokers are negligible. The questionnaire showed to have a good internal consistency (Cronbach α =.929). On the total group, significant statistically differences were found for all the dimensions regarding age, sex, study specialty and university. Physical activity was associated with healthier lifestyles choices. Geographical-induced differences were found (eating and sleep behaviours, alcohol awareness) as well as socio-economic differences. Female students shown to be more stressed than males. Occupational wellness increased by age. Sport students shown more health awareness. Many of the differences found in the total group disappeared when comparing only sport students of the two university, showing females increasing their scores. This result can be explained by a masculinization effect of sport.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p< 0.0001) and NAC+Pb groups (p<0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

This study compares lifestyles behaviour in Italian and Latvian university students, to assess if there are differences for sex, age, university or studies specialties. An online questionnaire investigating 8 lifestyle dimensions has been compiled by 156 (43,6 % females) from Italy and 105 from Latvia (82,9% females). Answers were collected between April and December 2020. Presence of smokers are negligible. The questionnaire showed to have a good internal consistency (Cronbach α =.929). On the total group, significant statistically differences were found for all the dimensions regarding age, sex, study specialty and university. Physical activity was associated with healthier lifestyles choices. Geographical-induced differences were found (eating and sleep behaviours, alcohol awareness) as well as socio-economic differences. Female students shown to be more stressed than males. Occupational wellness increased by age. Sport students shown more health awareness. Many of the differences found in the total group disappeared when comparing only sport students of the two university, showing females increasing their scores. This result can be explained by a masculinization effect of sport.

Rats, including those of the Sprague Dawley strain, may kill mice. Because of this muridical behavior, it is standard practice in many research animal housing facilities to separate mice from rats (i.e., the predators) to minimize stress for the mice. We therefore tested the effect of cohousing on the stress levels of mice from either the C57BL/6J (BL6) or the CD1 strain and Sprague Dawley (SD rat) by determining their fecal corticosterone or cortisol metabolites (FCM) concentration and investigated how cohousing impacts a behavioral assay, i.e., conditioned place preference for intragenus (i.e., mouse-mouse or rat-rat) dyadic social interaction (DSI CPP) that had been shown be sensitive to social factors, especially to handling by humans. We found that the two delivery batches of BL6 mice or SD rats, respectively, had different stress levels at delivery that were statistically significant for the BL6 mice. Even so, the BL6 mice cohoused with rats had significantly increased FCM concentrations, indicative of higher stress levels, as compared to (1) BL6 mice housed alone or (2) BL6 mice at delivery. In contrast to their elevated stress levels, the attractiveness for contextual cues associated with mouse-mouse social interaction (DSI CPP) even increased in rat-cohoused BL6 mice, albeit nonsignificantly. Thus, cohousing BL6 mice and rats did not impair a behavioral assay in BL6 mice that had proved to be sensitive to handling stress by humans in our laboratory. SD rats cohoused with BL6- or CD1 mice and CD1 mice cohoused with SD rats showed DSI CPP that was not different from our previously published data on SD rats and BL6 mice of the Jackson- or NIH substrain obtained in the absence of cohousing. Our findings suggest that the effect of cohousing rats and mice under the conditions described above on their stress levels as opposed to their behavior might be less clearcut than generally assumed and might be overriden by conditions that cannot be controlled, i.e., different deliveries. Our findings can help to use research animal housing resources, which usually are limited, more efficiently.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia giving rise to oligodendrocytes, the myelin forming cells in the central nervous system (CNS). While OPCs are highly proliferating during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated, they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar, a barrier mainly formed by reactive astrocytes, microglia, and the deposition of inhibitory extracellular matrix components. If, on one hand, glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

Memristors were proposed in the early ’70s of the XXth century by Leon Chua as a new electrical element linking the charge and the flux. Since that first introduction, these devices have positioned themselves to be considered as possibly fundamental for the new generations of electronic devices. It has to be mentioned that actual memristors have only been recognized to exist as physical elements. In this paper, we apply a modeling framework to generate a model describing experimental measurements performed on a ReRAM. We show how to apply the Dynamic Route Map technique in the general case to obtain an approximation to the differential equation that determines the behaviour of the device.

Most recent university campuses follow the North American model, built on city limits or countryside, with large separate buildings in open green spaces. Studies suggest that prevalence and severity of mental health issues among university students are increasing over the past decade in most countries. University services were created to face this growing problem, however individual based interventions have limited effects on mental health and well-being of a large population. Our aim was to verify if and how the natural environment in Campuses is focused on programs to cope with the issue of mental health and well-being among students. Systematic review of literature was undertaken with search in Scopus and LILACS with the keywords “green areas” AND “well-being” AND “Campus”, following PRISMA guidelines. As a result, 32 articles were selected. Research on the topic is recent, mostly in the USA, Bulgaria, and China. Most studies used objective information on campuses’ greenness and/or university students’ perception. Mental health was usually measured by validated scores. Findings of all the studies indicated positive association between campus greenery and well-being of students. We conclude that there is a large potential for use of university campuses in programs and sites for students´ restoration and stress relief.

In this short communication, following a brief introduction, we undertake a comprehensive analytical study of the weighted Simpson index. Our primary emphasis concerns the precise determination of the optimal point (minimizer) coordinates and of the minimum value of the index, a differentiable convex function, which is related to the harmonic mean concept. Furthermore, we address and solve the inversion problem and show the tight connection between both approaches. Last, we give some insights and final remarks on this subject.

The purpose of this paper is to examine if there are links between interpersonal trust and competences, relations and cooperation in Polish telecom companies. It examines what factors affect trust in coworkers and managers in sustainable organizations. The paper surveys a sample of 175 employees of telecom companies in Poland by means of a questionnaire. The results indicate that the competences, relations and cooperation are related to interpersonal trust. Regression analysis showed that the competences and relations predict a significant variance in trust amongst coworkers. Additionally, cooperation contributes to prediction of trust in mangers. Given the importance of trust in sustainable organizations, a better comprehension of what factors are related to team confidence provides valuable information for stakeholders. The results provide valuable clues how to improve interpersonal trust in sustainable organizations.

Understanding tourist behaviour during and after major tourism crises is essential to help destinations recover. The COVID-19 pandemic, a period of uncertainty and risk, makes it relevant to assess factors that influence travel intentions. There has been little research on tourist behaviour during health crises and, in particular, on perceived health risk and uncertainty effects on travel intentions. This study was carried out during the first months of the pandemic in Brazil and aims to investigate the role of health risk perception and intolerance of uncertainty on travel intentions for 2020 and 2021. We applied an online survey to 1,150 Brazilian participants from March to May of 2020. Our findings indicate that perceived COVID-19 severity, perceived probability of contracting it, and expected pandemic duration are significant predictors of travel intentions for both years. This paper sheds new light on tourist behaviour in the context of global health crises.

Plasma medicine is a new field focusing on biomedical and clinical applications of cold physical plasmas, including their anticancer effects. Cold plasmas can be applied directly or indirectly as plasma activated liquids (PAL). The effect of plasma activated cell growth medium (PAM) and plasma activated phosphate buffered saline (PAPBS) were tested using a plasma pen generating streamer corona discharge in ambient air, on different cancer cell lines (melanoma A375, glioblastoma LN229 and pancreatic cancer MiaPaCa-2) and normal cells (human dermal fibroblasts HDFa). The viability reduction and apoptosis induction were detected in all cancer cells after incubation in PAL. In melanoma cells we focused on detailed insights to the apoptotic pathways. The anticancer effects depend on the plasma treatment time or PAL concentration. The first 30 minutes of incubation in PAL were enough to start processes leading to the cell death. In fibroblasts, no apoptosis induction was observed, only PAPBS, activated for longer time, slightly decreased their viability. Anticancer effects of PAM and PAPBS on cancer cells showed selectivity compared to normal fibroblasts, depended on correctly chosen activation time and PAL concentration. This selectivity, supported by optimum ratio of hydrogen peroxide and nitrites in PAL, is very promising for potential clinical applications.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

This scholarly article introduces the "Change Through Play: Rethinking Masculinity" program, a potential intervention designed to address gun violence in the United States by targeting its societal roots, particularly through the lens of gender socialization. The program focuses on transforming children’s, particularly young boys', perceptions of masculinity away from gun violence by influencing the types of toys they play with. By promoting non-violent play, the initiative aims to foster a future generation less inclined to engage in gun violence. This community-interactive and educational approach emphasizes the importance of evidence-based interventions that respect community values and cultural dynamics. The program employs a mixed-methods approach, combining qualitative and quantitative research to evaluate its effectiveness. The program highlights the necessity of sustained, collective action to transform the entrenched practices and beliefs that perpetuate violence, ultimately striving for a society that prioritizes peace, justice, and safety.

. Gut microbiome reflects healthy and predicts possible disease in hosts. A holistic view of this community is needed, focused on identification species, and on the dissection of how species interact with their host and with each other, regardless of whether their presence is beneficial, inconsequential, or detrimental. Distribution of gut-associated eukaryotes within and across NHPs is likely driven by host behavior and ecology. To ascertain the existence of free-living amoebae (FLA) in the gut of wild and captive non-human primates (NHPs), 01 sample stools were collected and submitted to culture-dependent and microscopy examination and DNA sequencing. FLAs were detected in 45.4% (46/101) of fecal samples analysed and their morphological characteristics matching those of Acanthamoeba spp, Vermamoeba spp, and fan-shaped amoebae of the family Vannellidae. Sequence analysis of the PCR- products revealed that the suspected amoebae are highly homologous (99% identity and 100% query coverage) with Acanthamoeba genotype T4 and Vermamoeba vermiformis amoebae. The results showed a great diversity of FLAs in the NHP microbiome, which may pose a potential risk to the health of NHPs. To the best of our knowledge, this is the first report the presence of FLAs in NHPs naturally infected. However, it is not known whether gut-borne FLA are exploiting a viable ecological niche, or whether they are simply transient residents in the gut.

Cervical cancer is the fourth most common type of cancer in the world that causes death in women. It is mainly caused by persistent infection by human papillomavirus (HPV) that triggers a chronic inflammatory process. Therefore, the use of anti-inflammatory drugs is a potential treatment option. The effects of piperine, an amino alkaloid derived from Piper nigrum, are poorly understood in cervical cancer inflammation, making it a target of research. This work aimed to investigate the antitumor effect of piperine on cervical cancer and to determine whether this effect is modulated by the cyclooxygenase 2 (PTGS2) pathway using in vitro model of cervical cancer (HeLa, SiHa, CaSki), and non-tumoral (HaCaT) cell lines. The results showed that, piperine reduces in vitro parameters associated with neoplastic evolution such proliferation, viability and migration by cell cycle arrest in the G1/G0 and G2/M phases, with subsequent induction of apoptosis. This action was modulated by downregulated of cyclooxygenase 2 (PTGS2) pathway, which in turn regulates the secretion of cytokines and the expression of mitogen activated protein kinases (MAPKs), metalloproteinases (MMPs), and their antagonists (TIMPs). These findings indicate the phytotherapeutic potential of piperine as complementary treatment in cervical cancer.

Pesticide exposure is a growing concern for public health. Although Brazil is the world's largest consumer of pesticides, few studies addressed the health effects among farmers. This study aimed to evaluate whether pesticide exposure is associated with respiratory outcomes among rural workers and relatives in Brazil during the crop and off-seasons. 82 family farmers were interviewed about occupational history and respiratory symptoms, and cholinesterase tests were conducted in the crop-season. Spirometry was performed during the crop and off-season. Respiratory outcomes were compared between seasons and multiple regressions were conducted to search for associations with exposure indicators. Participants were occupationally and environmentally exposed to multiple pesticides from an early age. During the crop and off-season, respectively, they presented a prevalence of 40% and 30.7% for cough, 30.7% and 24% for nasal allergies, and 24% and 17.3% for chest tightness. Significant relations between spirometry impairments and exposure indicators were found both during the crop and off-season. These findings provide complementary evidence about the association of pesticide exposure with adverse respiratory effects among family farmers in Brazil. This situation requires special attention as it may increase the risk of pulmonary dysfunctions, and the morbidity and mortality burden associated with these diseases.

Humans learn from a lot of information sources to make decisions. Once this information is learned in the brain, spatio-temporal associations are made, connecting all these sources (variables) in space and time represented as brain connectivity. In reality, to make a decision, we usually have only part of the infor-mation, either as a limited number of variables, or limited time to make the decision, or both. The brain functions as spatio-temporal associative memory. Inspired by the ability of the human brain, a brain-inspired spatio-temporal associative memory was proposed earlier, that utilizes the NeuCube brain-inspired spiking neural network framework. Here we apply the STAM framework to develop STAM for neuroimaging data, on the cases of EEG and fMRI, resulting in STAM-EEG and STAM-fMRI. The paper shows that once a NeuCube STAM classification model is trained on a complete spatio-temporal EEG or fMRI data, it can be recalled using only part of the time series, or/and only part of the used variables. We evaluate accordingly the temporal association accuracy and spatial association accuracy. This is a pilot study that opens the field for the development of multimodal classification systems on other multimodal neuroimaging data, such as the also shown longitudinal MRI data, trained on complete data, but recalled on partial data collected across different settings, in different labs and clinics, that may vary in terms of variables, time of data collection, and other parameters. The proposed methods will allow also for brain diagnostic/prognostic marker discovery using spatio-temporal neuroimaging data.

Historically the use of artificial intelligence (AI) in paediatrics dates back to 1984 with the intro-duction of a computer-assisted medical decision-making system called SHELP. Since then, research on the use of AI in pediatrics has become much more popular, and the number of reviewed publications largely increased. Consequently, a need for a holistic research landscape enabling researchers and other interested parties to gain insights into, deepen their knowledge about or inform them about the use of AI in pediatrics arised. To fill this gap a novel methodology named synthetic knowledge synthesis was applied. Using SKS we identified most prolific countries, in-stitutions, source titles, funding agencies, research themes, research gaps and hot spots.

The possibility of using additive manufacturing (AM) in the medicine area has created a new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described herein a medical-grade thermoplastic polyurethane (S-TPU), which was developed and then formed into a filament for Fused Deposition Modeling (FDM) 3D printers during a melt-extrusion process. S-TPU consisting of aliphatic hexamethylene 1,6-diisocyanate (HDI), amorphous α,ω-dihydroxy(ethylene-butylene adipate) (PEBA) and 1,4 butandiol (BDO) as a chain extender, was synthesized without the use of a catalyst. The filament properties were characterized by rheological, mechanical, physico-chemical and in vitro biological properties. The tests showed biocompatibility of the obtained filament as well as revealed no significant effect of the filament formation process on its properties. This study may contribute to expanding the range of medical-grade flexible filaments for standard low-budget FDM printers.

Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ), remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy (ITZ+KI) com-pared with ITZ monotherapy. Cats were randomly allocated in two treatment groups: G1 - ITZ 100 mg/cat/day and G2 - ITZ 100mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicates that clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered as the first-line treatment in the presence of negative predictors.

The aim of this paper is to study the main areas in which Artificial Intelligence (AI) will impact the field of project management that relates to cost, risk and scheduling. The research model was based on a previous study of the ten project management knowledge areas presented in the PMI’s PMBOK 6th edition where project schedule-, cost- and risk management knowledge areas were identified as being the ones most likely to be affected by the development of AI. A group of experts that participated in the study agreed that AI will affect the project management profession in the future. Different elements of the three knowledge areas were considered to be affected more by AI than others. The schedule baseline is the element believed to be affected the most out of the project schedule management elements. For project cost management, the estimation of resource cost is believed to be affected the most. In the case of project risk management, the application of AI will have the strongest impact on the probability and impact format.

This paper maps the causes of the demographic, economic and social decline of a selected border micro-region during the last century. The decline occurred due to the location being remote, lacking natural resources and having an unsuitable industrial structure. Historical events associated with the post-war deportation of the German population and efforts to create a classless society also played a role in the decline. The results are an 87% population decrease, the demise of most companies, a very low level of human capital and unemployment reaching up to 5%. In order to comprehend the current state of the border micro-region and predict future development, it is necessary to understand the development that has occurred since approximately the middle of the nineteenth century. The European countryside is certainly not homogeneous, and different regions have shown unique mixes of positional, natural, economic and political factors. Some hope has been raised in relation to the transition to a post-productive economy, a transition that turns the remoteness of the region into an advantage. This is confirmed by the positive migration balances of the smallest municipalities in the last decade.

Keywords: Forest management; sustainability; FSC; PEFC; research; market share

Groundwater habitats in the Dinaric Karst are home to the only known cave-adapted genus of bivalve mollusks, which currently survives as three distinct species with a highly fragmented distribution. Over the past few decades, Congeria populations suffered a steep decline across their range, as a result of human activities. Here, we identify the most pressing issues concerning the current conservation status of Congeria and identify key priorities for its scientific study. The building of dams and other hydrotechnical constructions have led to a significant decrease in the water inputs that used to supply underground systems where Congeria lives, contributing to a reduction of the cave habitats feasible for bivalve settlement. This is relatively well documented in Popovo polje where, as a result of hydrotechnical interventions on Trebisnjica river, water level drop destroyed well over 99 % of Congeria kusceri population in Zira cave and caused their complete disappearance in other caves. Similar factors are likely to have also affected the sister species Congeria jalzici in the Lika region. In addition, the salinization of Neretva river, lack of proper wastewater management, intense agriculture, tourist exploitation, and additional hydrotechnical plans add to the ongoing decline of the quality of Congeria habitats. These threats are expected to least to drastic reductions in population size within the next few decades, and this situation might be further aggravated by the lack of regulations and active measures for Congeria protection, as well by the limited understanding of its biology. Future scientific studies should be aimed at better elucidating microhabitat preference, defining the range of tolerance of environmental parameters, and assessing the size and genetic viability of existing Congeria populations. However, we highlight that these efforts would most certainly require the collaboration of local authorities and the allocation of appropriate financial resources in order to be effective.

Existing literature on the relationship between ride-hailing (RH) and transit services is limited to empirical studies that lack real-time spatial contexts. To fill this gap, we took a novel real-time geospatial analysis approach. With source data on ride-hailing trips in Chicago, Illinois, we computed real-time transit-equivalent trips for all 7,949,902 ride-hailing trips in June 2019; the sheer size of our sample is incomparable to the samples studied in existing literature. An existing Multinomial Nested Logit Model was used to determine the probability of a ride-hailer selecting a transit alternative to serve the specific O-D pair, P(Transit|CTA)[1]. We find that 31% of ride-hailing trips are replaceable, whereas 61% of trips are not replaceable. The remaining 8% lie within a buffer zone. We measured the robustness of this probability using a parametric sensitivity analysis and performed a two-tailed t-test. Our results indicate that of the four sensitivity parameters, the probability was most sensitive to the total travel time of a transit trip. The main contribution of our research is our thorough approach and fine-tuned series of real-time spatiotemporal analyses that investigate the replaceability of ride-hailing trips for public transit. The results and discussion intend to provide perspective derived from real trips and we anticipate that this paper will demonstrate the research benefits associated with the recording and release of ride-hailing data. [1] This value defines the replaceability of the trip, where a value ranging from 0 to 0.45 is considered not-replaceable (NR), and a value ranging from 0.55 to 1.0 is considered replaceable (R).

Microplastic pollution (MP) in marine environments around the globe is severe and enough precautions have not been taken so far for its prevention. The focus of this study is to quantify MPs from beach sediment and seawater samples and to identify their distribution and types along the western coast of Sri Lanka from the Kelani River estuary to the Mahaoya estuary. Nine sites along this 42 km stretch were selected and random sampling was employed to collect a minimum of 8 sediment samples from each site between October and December 2021. Water samples were also collected, parallel to the sediments, from the ocean surface. FTIR analysis revealed that most of the MPs found were polyethylene(PE), polypropylene(PP), polystyrene(PS), polyethylene terephthalate(PET), and phenol formaldehyde resin. The mean abundance of MPs varied from 2.0 ± 0.6 items/L to 161.0 ± 15.7 items/L in water samples and, from 3.0 ± 0.3 items/m2 to 656.0 ± 34.5 items/m2 in sediment samples. The MPs found were identified in different shapes as fragments (80.2%), pellets (14.9%), fibers (2.7%) and foams (2.5%). Analysis revealed that the beach sediments were contaminated with PS, phenol formaldehyde resin, PET, PP and PE, while surface seawater is dominated by phenol formaldehyde resin, PS, PP and PE.

The main purpose of this article is to identify key areas of research on climate change in the context of the SDGs, focusing on the potential development impacts on Bolivia and Paraguay. Application of the Delphi technique with the involvement of a panel of experts allowed the consolidation of different perspectives and knowledge on climate change, focusing on those that experts considered to have the greatest potential impact on the regions. The results of this study constitute a valuable guide for decision-makers and funding bodies, highlighting research areas that could have a significant impact at the national and regional levels, as well as for researchers, identifying specific research areas crucial for regional development and climate change mitigation.

Most research on colostrum quality and colostrum management focuses on maternal IgG transfer to the newborn calf. However, in addition to being a source of antibodies, colostrum has other components that influence passive immune transfer, nutrition, gut maturation, and thermoregulation. In this review, the constituents in the bovine colostrum, as well as their variation, are explored and it is discussed the biological role of colostrum on the newborn calf. Protein is the nutrient in higher concentration and fat is the nutrient with the most variation. There is a pronounced amplitude in the total solids content of colostrum, but the average concentration does not vary much between studies (24.7%). Bovine colostrum major components can vary with several factors, such as the region, season, breed, dry period length, and nutritional aspects of the dam. Bioactive components, cells, and microbiome variability are less understood, besides IgG. Regardless, they play crucial distinct roles in the physiological development of the newborn. However, a multi-interactive effect between these components, cells, and microorganisms is more likely to occur. Recently researched components in colostrum like miRNA, nucleo(t)sides, the milk fat globule membrane, oligosaccharides, minor proteins, and the microbiome are examples of promising interest areas of study.

The current management of colorectal cancer liver metastasis (CRCLM) patients involves a multidisciplinary approach with surgical resection remaining the primary curative option. The advances in liver surgery have improved outcomes, enabling more patients to undergo surgery successfully. In addition, the development of imaging software has improved the preoperative planning and patient selection for surgery and other interventions. Systemic therapies, such as targeted therapies and immunotherapies have enhanced the chances of complete resection. Targeted agents in combination with chemotherapy, have shown efficacy in downstaging tumors and increasing resectability.

Nowadays, frameworks and models are critical to enabling organizations to identify their current sustainability integration into business and to follow up on these initiatives over time. In this context, the maturity models offer a structured way of analyzing how a supply chain meets specific sustainability requirements and which areas demand attention to reach maturity levels. This study proposes a five-level maturity model to help supply chains identify their level of engagement with sustainability practices combining three perspectives: intra and inter-organizational sustainability practices, triple-bottom-line approach and critical areas for sustainability. All the steps followed in constructing the maturity model were based on a literature review, and case studies supported its improvement, application, and testing. The proposed model presents many advantages, such as being used as a self-assessment tool, a roadmap for sustainability behaviour improvement, and a benchmarking tool to evaluate and compare standards and best practices among organizations and supply chains.

The aim of this article is to summarize recent bioinformatic and statistical developments applicable to NMR-based metabolomics. Extracting relevant information from large multivariate datasets by statistical data analysis strategies may be of considerable complexity. Typical tasks comprise for example classification of specimens, identification of differentially produced metabolites, and estimation of fold changes. In this context it is of prime importance to minimize contributions from unwanted biases and experimental variance prior to these analyses. This is the goal of data normalization. Therefore, special emphasize is given to different data normalization strategies. In the first part, we will discuss the requirements and the pros and cons for a variety of commonly applied strategies. In the second part, we will concentrate on possible solutions in case that the requirements for the standard strategies are not fulfilled. In the last part, very recent developments will be discussed that allow reliable estimation of metabolic signatures for sample classification without prior data normalization. In this contribution special emphasis will be given to techniques that have worked well in our hands.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relation exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms." Bibliographic references from relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

We describe a competitive colorimetric assay that enables rapid and sensitive detection of galactose and reduced nicotinamide adenine dinucleotide (NADH) via colorimetric readouts and demon-strates its usefulness for monitoring NAD+-driven enzymatic reactions. We present a sensitive plasmonic sensing approach for assessing galactose concentration and the presence of NADH using galactose dehydrogenase immobilized gold nanostars (AuNS-PVP-GalDH). The AuNS-PVP-GalDH assay remains turquoise blue in the absence of galactose and NADH; however, as galactose and NADH concentrations grow, the reaction well color changes to a characteristic red color in the presence of an alkaline environment and metal ions catalyst (detection solution). As a result, when galactose is sensed in the presence of H2O2, the colored response of the AuNS-PVP-GalDH assay transforms from turquoise blue to light pink, then to wine red in a con-centration-dependent manner discernible to the human eye. This competitive AuNS-PVP-GalDH assay could be a viable analytical tool for rapid and convenient galactose quantification in re-source-limited areas.

The introduction on Zinc oxide nanoparticles (ZnOn) in sunscreens solved the issue of poor spreadability of these formulations, which often left a white film on the skin. However, safety concerns have arisen regarding the topical application of ZnOn. Some studies employed commercial sunscreens to address the safety issues of the topical application of ZnOn; however, commercial formulations are often complex and contain a wide range of ingredients that could attenuate the potential damage caused by the ZnOn. Therefore, in this study we aimed to develop a simple stable formulation containing 20% of coated and uncoated ZnOn, characterize the formulations and the nanoparticles, and assess the skin penetration in Franz diffusion cell. The Feret's diameter for the uncoated and coated ZnOn was 137 nm and 134 nm, respectively. For the uncoated ZnOn the hydrodynamic size in water was 368 nm and for the coated ZnOn, the average hydrodynamic size in ethyl acetate was 135 nm. The incorporation of ZnOn led to formulations more consistent and easier to spread, as suggested by the lower work of shear and higher values of firmness, cohesiveness, consistency and index of viscosity compared with the vehicle. The stability assessment at 45ºC suggested that the formulations containing the ZnOn were stable for 30 days and the vehicle was stable for 90 days. The assessment off the skin penetration by reflectance confocal laser microscopy indicated that the formulations did not permeate into the deepest layers of the skin, but accumulated on the skin furrows, hair and hair follicle.

Acne vulgaris is a prevalent dermatological disorder that impacts the quality of life for millions of people around the world. The multifactorial nature of this disorder requires innovative and effective treatment strategies. Over time, there has been a growing interest regarding the use of natural topical therapies, with cannabinoids emerging as a promising group of compounds for investiga-tion. In the context of acne treatment, cannabinoids are of particular interest due to their anti-acne properties, namely, lipostatic, anti-inflammatory, antiproliferative, and antimicrobial activities. Among these bioactive compounds, cannabidiol stands out as a notable derivative, exhibiting a promising spectrum of therapeutic actions. Pre-clinical and clinical studies have proven its ability to modulate sebum production, reduce inflammation, and inhibit bacterial proliferation - all of which are critical components in the pathogenesis of this dermatosis. This review provides a comprehen-sive overview of cannabinoids' potential as a novel and holistic approach to acne vulgaris treatment and summarizes recent developments in this area.

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of death due to cancer. About 30% of patients with PCa who have been castrated develop a castration-resistant form of the disease (CRPC), which is incurable. In the last decade, new treatments that control the disease have emerged, slowing progression and spread, and prolonging survival while maintaining the quality of life. These include immunotherapies; however, we do not yet know the optimal combination and sequence of these therapies with the standard ones. All therapies are not always suitable for every patient due to co-morbidities or adverse effects of therapies or both, so there is an urgent need for further work on new therapeutic options. Advances in cancer immunotherapy with an immune checkpoint inhibition mechanism (e.g., ipilimumab, an anti-CTLA-4 inhibitor) have not shown a survival benefit in patients with CRPC. Other immunological approaches have also not given clear results, which has indirectly prevented breakthrough for this type of therapeutic strategy into clinical use. Currently, the only approved form of immunotherapy for patients with CRPC is a cell-based medicine, but it is only available to patients in some parts of the world. Based on the experience gained from recently completed clinical research on immunotherapy with dendritic cell-based immunohybridomas, the aHyC dendritic cell vaccine, for patients with CRPC, we highlight the current status, and possible alternatives that should be considered in the future.

Carbon monoxide (CO) is a cytoprotective endogenous gas that is ubiquitously produced by the stress response enzyme heme-oxygenase. Being a gas, CO rapidly diffuses through tissues and binds to hemoglobin (Hb) increasing carboxyhemoglobin (COHb) levels. COHb can be formed in the erythrocytes or in plasma from cell-free Hb. Herein, it is discussed whether endogenous COHb is or is not an innocuous and inevitable metabolic waste product and it is hypothesized that COHb has a biological role. In the present review literature data is presented to support this hypothesis based on two main premises: (i) there is no direct correlation between COHb levels and CO toxicity; and (ii) COHb seems to have a direct cytoprotective and antioxidant role in erythrocytes and in hemorrhagic models in vivo. Moreover, CO is also antioxidant by generating COHb, which protects against the pro-oxidant damaging effects of cell free Hb. Up to now COHb has been considered as a sink for both exogenous and endogenous CO generated during CO intoxication or heme metabolism, respectively. Hallmarking COHb as an important molecule with a biological (and eventually beneficial) role is a turning point on CO Biology research, namely in CO intoxication and CO cytoprotection.

Due to the use of structural and seismic techniques an attempt has been made in this study to determine the hydrocarbon potential and future exploration in Pakistan's Lower Indus basin area and offshore region. In addition to the possibility of hydrocarbon accumulation, the major goals of this research are to analyze structural patterns in the subsurface of the study region, identify the horizons of various formations using surface seismic, and interpret seismic lines. Seismic data has been used to find and integrate the exposed Cretaceous/Tertiary basalt at Ranikot in the lower Indus basin to the well-known Deccan basalts of the Indo-Pak plate, which is the secondary goal of the current investigation. According to the interpretation of seismic data, the Indo-Pakistan plate has experienced rifting because of tectonic activity. Graben and horst structures have been identified in the study area horizon, which indicates that the area has undergone major structural and depositional changes. While faults provide a pathway for hydrocarbons to migrate from their source to reservoir rock, grabens are principally responsible for the accumulation of hydrocarbons. We further deduce that the prior exploration failures in the area were due to a lack of knowledge of the subsurface formations and structural trends, which are essential for characterizing the hydrocarbon play and trap features. Our results can be productive for the local hydrocarbon drilling projects as well as worldwide tectonic stratigraphy studies on passive continental edges.

Intussusceptive pillars, regarded as a hallmark of intussusceptive angiogenesis, have been described in developing vasculature of many organs and organisms. The aim of this study was to resolve the question about pillar formation and their further maturation employing zebrafish caudal vein plexus (CVP). The CVP development was monitored by in vivo confocal microscopy in high spatio-temporal resolution using the transgenic zebrafish model Fli1a:eGPF//Gata1:dsRed. We tracked back the formation of pillars (diameter ≤4µm) and intercapillary meshes (diameter >4µm) and analysed their morphology and behaviour. Transluminal pillars in the CVP arose by a combination of sprouting, lumen expansion, and/or by creation of intraluminal folds, and those mechanisms were not associated directly with blood flow. The follow-up of pillars indicated that one third of them disappeared between 28-48 hours post fertilisation (hpf) and of the remaining ones only 1/17 changed their cross-section area by >50%. The majority of the bigger meshes (39/62) increased their cross-section area by >50%. Plexus simplification and establishment of hierarchy was dominated by the dynamics of intercapillary meshes, which formed mainly by sprouting angiogenesis. These meshes were observed to grow, reshape, and merge with each other. Our observations suggested an alternative view on intussusceptive angiogenesis in the CVP.

Surimi consists in a technique for concentrating myofibrillar proteins with gelling ability, which aims to make use of by-products from fish slaughter, such as bullfrog back, which can be basis for the manufacture of emulsified products. Due to the strategic need to develop clean label foods, products such as collagen have been reported as potential natural additives with bioactive properties. The objective was to elaborate a surimi from the mechanically separated bullfrog back and to develop an emulsion, replacing the soy lecithin used by hydrolyzed collagen, evaluating its emulsifying and antioxidant potential during 120 days of storage under freezing. Three meat emulsions were prepared: EC0 (100% soy lecithin), EC50 (50% soy lecithin + 50% collagen), and EC100 (100% collagen), which were subjected to analysis of chemical composition, emulsion stability, water holding capacity, luminosity, whiteness, texture profile, TBARS and antioxidant activity. Insertion of collagen increased whiteness, lightness, hardness, and chewiness values compared to the EC0, but showed greater fluid loss. All treatments showed stable WHC values (88 – 91%) over time. Replacement with collagen was satisfactory as an emulsifier and as an antioxidant, and the EC50 and EC100 treatments were not negatively affected in the investigated parameters.

Academic publishing is undergoing a highly transformative process, and many rules and value systems that were in place for years are being challenged in unprecedented forms leading to the evolution of novel ways of dealing with new pressures. One of the most important aspects of an integrated and valid academic literature is the ability to screen publications for errors during peer review to weed out mistakes, fraud and inconsistencies, such that the final published product represents a product that has value, intellectually, and otherwise. It is difficult to claim the existence of perfect manuscripts. The level of errors that exist in a manuscript will depend on the rigor of the research group and of the peer review process that was used to screen that paper. When errors slip into a final published paper, either through honest error or misconduct, and are not detected during peer review and editorial screening, but are spotted during post-publication peer review, an opportunity is created to set the record straight, and to correct it. To date, the most common forms of correcting the literature have been errata, corrigenda, expressions of concern, and retractions. Despite this range of corrective measures, which represent artificially created corrals around pockets of imperfect literature, certain cases do not quite fit this mold, and new suggested measures for correcting the literature have been proposed, including manuscript versioning, amendments, partial retractions and retract and replace. In this commentary, a discussion of the evolving correction of the literature is provided, as are perspectives of the risks and benefits of such new measures to improve it.

Viruses with encephalitogenic potential can cause neurological conditions of clinical and epidemiological importance, such as Saint Louis encephalitis virus, Venezuelan equine encephalitis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, dengue virus, Zika virus, Chikungunya virus, Mayaro virus and West Nile virus. The objective of the present study was to determine the number of arboviruses with neuroinvasive potential isolated in Brazil that corresponds to the collection of viral samples belonging to the Section of Arbovirology and Hemorrhagic Fevers (SAARB/IEC) of the Laboratory Network of National Reference for Arbovirus Diagnosis from 1954 to 2022. A total of 1,090 arbovirus samples with encephalitogenic potential were isolated from mice. From a total of 7,054 samples intended for cell culture. The isolates from mosquitoes totaled 659 viruses. The emergence of new arboviruses may be responsible for diseases still unknown to humans, making the Amazon region a hotspot for infectious diseases due to its fauna and flora species characteristics. The detection of circulating arboviruses with the potential to cause neuroinvasive diseases is constant, which justifies the continuation of active epidemiological surveillance work that offers adequate support to the public health system regarding the virological diagnosis of circulating arboviruses in Brazil.

This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this special issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need of great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is sometimes overlooked with non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented

Nowadays, the growing concern about improving thermal comfort in textiles, asphalt pavements and buildings has stimulated research into phase change materials (PCMs). However, the incorporation of PCMs directly causes mechanical impacts. Therefore, this study herein reported focuses on designing coaxial phase change fibres using commercial cellulose acetate (CA) or recycled CA obtained from cotton fabrics (CAt) as a coating and polyethylene glycol (PEG) 2000 as a core. The phase change fibres (PCF) were produced by wet spinning, varying the parameters: (i) CA concentration, molecular weight and source (virgin versus recycled); and (ii) PEG concentration and ejection. For phase change recycled fibres (PCFt), PEG concentration and ejection were varied. The fibres were assessed for their optical, chemical, thermal and mechanical properties. Bright-field microscopy images and Scanning Electron Microscopy (SEM) micrographs proved the coaxial structure. Fourier Transform Infrared spectroscopy (FTIR) confirmed the presence of PEG in the core. Thermogravimetric Analysis (TGA) proved the ability of PCFs to tolerate high temperatures. Differential Scanning Calorimetry (DSC) attested to the presence of PEG2000 peaks, since their melting points were close to those of virgin PEG2000, with a slight change in the PCFs and PCFts caused by the protective sheath of CA and CAt.

Transitioning towards net zero emissions is critical in the chemical and process industries to combat climate change and ensure environmental sustainability. Key focus areas of this review include the reduction of carbon emissions, the efficient utilization of energy resources, and the adoption of sustainable practices. Cutting-edge technologies such as biomass utilization, biotechnology applications, and waste management strategies are crucial in achieving this transition. Industries, including cement production, encounter unique challenges in their quest for sustainability and must actively seek innovative solutions to mitigate their carbon footprint effectively. The role of hydrogen as a clean fuel and its potential to revolutionize the chemical and process sectors is also discussed. The European Green Deal and Sustainable Development Goals (SDGs) are significant for the chemical industry. They provide a clear roadmap and framework for promoting sustainability, driving innovation, and reducing the industry's environmental impact. By aligning with these initiatives, the chemical industry can enhance its competitiveness, contribute to societal well-being, and foster collaboration across sectors to achieve shared sustainability objectives.

The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in babies of ZIKV-infected women. This study provides a descriptive analysis, since the onset of symptoms to the delivery, of a cohort who were registered as having ZIKV infection in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Brazilian Amazonian region. A total of 834 women with suspected ZIKV in pregnancy were included, of whom 91.4% had confirmed pregnancy. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKV infection in 42.2% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (abortion, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (4.96%) and ZIKV-negative (2.15%) cases. Women with suspected ZIKV infection were much more likely to have adverse pregnancy outcomes if they were symptomatic during the first trimester of pregnancy (odds ratio 10.5; 95% confidence interval 4.0–27.0; p<0.001). Among pregnant women with suspected ZIKV infection, the occurrence of symptoms in the first trimester is associated with an especially high risk of severe adverse pregnancy outcomes.

Climate change in the coming decades could intensify extreme events such as severe droughts. Combined with the possible increase of water demands, these changes exert a large pressure on the water systems. In order to confirm this assumption, a set of scenarios was proposed in this study to consider the combined impact of climate changes and the increase in water demand on the main multiple-use reservoirs of São Francisco River, Brazil. For this purpose, five CMIP6 climate models were used considering two greenhouse gas emissions scenarios: the SSP2-4.5 and SSP5-8.5. The naturalized and withdraw streamflows were estimated to the adopted reser-voirs considering all existing, new and projected demands. The conjunction of scenarios indicat-ed an increase in Potential Evapotranspiration, a possible significant reduction in water availa-bility, a growth in water demand mainly for irrigation and a substantial reduction in the perfor-mance of the evaluated reservoirs.

Recent years have shown that traditional regulatory techniques alone are not effective in achieving behavior change in important fields such as environmental sustainability. Governments all over the world have been progressively including behaviourally informed considerations in policy and law-making with the aim of improving the acceptance and impact of sustainability-oriented measures. This led to the arrival of alternative regulatory tools, such as nudges. The effectiveness of nudges for environmental sustainability (green nudges) has been largely reported but the practical and ethical implications are still largely neglected by academic research. In this contribution, “nudges” are conceptually distinguished from “boosts” and their ethical briefly explained. The analysis is made at the light of the current mostly European and US American academic literature.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

Urban tourism has witnessed significant growth in recent years, driven by various factors that foster the transformation of urban areas into tourist hotspots. These factors include a rising interest in culture and heritage, ongoing urban redevelopment and conversion processes, and the introduction of new experiences and activities. Two particularly influential factors contributing to this growth are low-cost travel, which facilitates more accessible access to urban destinations, and the emergence of new types of accommodation, such as short-term rental (also known as local accommodation or Airbnb-type accommodation). This sudden and continuous growth of this type of tourist accommodation brings new challenges to cities and local communities. On the positive side, it contributes to job opportunities, the dynamism of the local economy, and urban revitalization. On the other hand, it also represents more difficulty in retaining the local population in city centers, as more and more buildings are converted into hostels and tourist apartments. In this context, it becomes essential to conduct studies evaluating the impacts of these dynamics in urban areas and how they influence residents' and visitors' perspectives. Therefore, this study aims to identify the main transformations resulting from short-term rental (STR) development, focusing on the impacts felt by tourists and residents in Porto. A questionnaire was distributed to tourists and residents in Porto's city center in June 2023. The results reveal differences in opinions between tourists and residents, particularly concerning historical heritage preservation, local population relocation, and reduced housing availability for residents. Nevertheless, there is a similarity in their opinions regarding the stimulus that local accommodation brings to the economy and the rehabilitation of buildings and urban areas. This study reinforces the need to pay more attention to the future development of tourist accommodation in city centers, especially regarding local policies and territorial planning, to balance better tourism development and local communities' quality of life.

The evolution of knowledge in biological and medical areas which made possible scientific and technological advances are attributed to anatomical studies, physiology and immunology in animals, contributing to the discovery of prophylactic measures and treatments of diseases that affect humans and animals. Currently, substitution is suggested by alternative methods that do not use laboratory animals, however in vitro methods may never be able to provide similar results to in vivo methods. Mice and rats are the most used animals in experimental researches, the anatomical, histological and genetic differences between species should be carefully evaluated, to better apply the study model and avoid unnecessary waste avoid. This study, aimed at an anatomical comparative and histological relationship between a rat´s and a mouse´s organs, is of great importance in experimental studies. For such, 30 Mus musculus (Swiss) mice and 15 Rattus norvegicus (Wistar) male and heterogenic rats, were used. All animals were kept free of pathogenic microorganisms, with the absence of surgical interventions that could cause anatomical and physiological changes. It was possible to observe significant anatomical and histological differences between spleens, brains, hearts, stomachs and intestines, livers, eyes, lungs and kidneys among species, which will serve as a basis to assist in choosing the most satisfactory research model. Few studies relate specific characteristics among laboratory animals, being restricted to a few veterinary and zoology books. The greater the organic, physiological and anatomical similarities are with the human being, the greater is the applicability of the animals in studies. However, it is not possible to lay down general rules to validate the extrapolation from one species to another.

(1) Background: In Eugenia Stipitata Mac Vaugh (Arazá), there is an abundance of flavonoids, carotenoids, and phenolic acids, which are bioactive compounds with antioxidant, anticarcinogenic, antimicrobial, anti-inflammatory, antispasmodic, antiulcer, and cardiovascular disease prevention benefits. Therefore, the aim of this review is to compile the compounds that have been identified in the fruit and gather information about secondary metabolites to establish their potential preventive and therapeutic effects; (2) Methods: a literature search was conducted in repositories and databases such as Science Direct, Scopus, PubMed, Web of Science, Agriculture Collection Gale, SAGE, OXFORD University, DOAJ, among others. Articles identifying and quantifying bioactive compounds present in Arazá were included; (3) Results: Five studies meeting the inclusion criteria were incorporated, resulting in the compilation of 82 compounds, of which 24 were identified and quantified, while 58 were solely identified. This review was able to identify and report the concentration, and in some cases, the quantity, of phenolic compounds with antioxidant and anti-inflammatory capabilities present in Arazá; (4) Conclusions: With this scope, it was possible to obtain a more comprehensive understanding of the fruit's potential to potentially enhance health aspects, thereby providing greater prominence and added value to this product, allowing for more frequent inclusion in the diets of consumers, and even enabling exportation.

Large office buildings are responsible for a substantial portion of energy consumption in urban districts. However, thorough assessments regarding the Nordic countries are still lacking. In this paper we analyse the largest dataset to date for a Nordic office building, by considering a case study located in Stockholm, Sweden, that is occupied by nearly a thousand employees.Distinguishing the lighting and occupants’ appliances energy use from heating and cooling, we can estimate the impact of occupancy without any schedule data. A standard frequentist analysis is compared with Bayesian inference, and the according regression formulas are listed in tables that are easy to implement into building performance simulations (BPS). Monthly as well as seasonal correlations are addressed, showing the critical importance of occupancy.A simple method, grounded on the power drain measurements aimed at generating boundary conditions for the BPS, is also introduced; it shows how, for this type of data and number of occupants, no more complexities are needed in order to obtain reliable predictions. For an average year, we overestimate the measured cumulative consumption by only 4.7%. The model can be easily generalised to a variety of datasets.

The authors introduce the GRASS GIS add-on module g.citation as an initial implementation of a fine-grained software citation concept. The module extends the existing citation capabilities of GRASS GIS, which until now only provide for automated citation of the software project as a whole, authored by the GRASS Development Team, without reference to individual persons. The functionalities of the new module enable individual code citation for each of the over 500 implemented functionalities, including add-on modules. Three different classes of citation output are provided in a variety human- and machine-readable formats. The implications of this reference implementation of scientific software citation for both for the GRASS GIS project and the OSGeo foundation are outlined.

The health benefits of extra virgin olive oil (EVOO) are related with its chemical composition and the presence of bioactive compounds with antioxidant properties. The aim of this study was evaluate antioxidant compounds (pigments, CoQ10 and phenolic compounds) and antioxidant properties of EVOO from the same region comparing different cultivars (Hojiblanca and Arbequina), harvest year and crop stage. Antioxidant properties of oils were studied before and after a gastrointestinal digestion process, by in vitro assays (DPPH, ABTS and FRAP) and antioxidant markers in Caco-2 cells (reactive oxygen species production). The content of bioactive compounds measured was significantly affected by cultivar and harvest year (except for carotenoids) and by the crop stage (except for coenzyme Q10). Higher amount of coenzyme Q10 was observed in Hojiblanca than in Arbequina EVOO. Total phenol content and antioxidant properties were also different depending on cultivar and harvest year and the in vitro digestion process strongly improved antioxidant marker values. Antioxidant potential in bioaccessible fractions was mainly related with content of coenzyme Q10 and phenolic compounds in EVOO. Chemometric analysis showed that the oils were clearly classified by cultivars, harvest and crop stage, according with chemical composition and antioxidant activity analyzed in the present study

In the present paper four passive micromixers designs (G1, G2, G3 and G4) inspired on distillation columns trays were proposed. The devices performance was assessed by numerical simulations. The mixing performance was investigated for a Reynolds number range from 0.01 to 100 and channel height of 200 µm, 500 µm and 1000 µm for oil/ethanol flow. G1 and G4 designs provided high mixing index (> 0.975). The G1 device achieved superior mixing performance with a moderate pressure drop (about 0.5 MPa) due to the induced flow recirculation pattern for a relative high flow rate of 0.21 L/min, highlighting the potential use of such microdevice for scale-up and numbering-up of microdevices in modular chemical plant processing.

Cryphonectria is a fungal genus associated with economically significant disease of trees. Herein we characterized a novel double-stranded RNA virus from the fungal species Cryphonectria naterciae, a species unexplored as a virus host. De novo assembly of RNA-seq data and Sanger sequencing of RACE (rapid amplification of cDNA ends) clones gave the complete, non-segmented genome (10,164 bp) of the virus termed Cryphonectria naterciae fusagravirus (CnFGV1) that was phylogenetically placed within the previously proposed viral family Fusagraviridae. Of 31 field-collected strains of C. naterciae, 40% tested CnFGV1-positive. Co-cultivation resulted in within-species transmission of CnFGV1 to virus-free strains of C. naterciae. Comparison of the mycelium phenotype and the growth rate of CnFGV1-infected and virus-free isogenic strains revealed frequent sectoring and growth reduction in C. naterciae. Co-culturing also led to cross-species transmission of CnFGV1 to Cryphonectria carpinicola and Cryphonectria radicalis, but not to Cryphonectria parasitica. The virus-infected C. naterciae and the experimentally infected Cryphonectria spp. readily transmitted CnFGV1 through asexual spores to the next generation. CnFGV1 strongly reduced conidiation and in some cases vegetative growth of C. carpinicola, which is involved in the European hornbeam disease. This study is the first report of a fusagravirus in the family Cryphonectriaceae and lays the groundwork for assessing a hypovirulence effect of CnFGV1 against the hornbeam decline in Europe.

Molecular studies regarding regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humanity, and it is still a challenge to prevent and treat it. The control of the infection as well as its diagnosis are still complex, and treatments used are linked to several side effects. This study aimed to investigate miRNA’s expression profile to identify possible biomarkers for tuberculosis. We applied NGS techniques to investigate miRNA’s global expression profile from blood samples of infected patients with tuberculosis, their respective healthy physicians, and external healthy individuals as controls. Samples from 22 individuals run through a differential expression, target genes, gene set enrichment, and miRNA-gene network analysis. We observed 153 altered miRNAs, among which, only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results propose that miRNAs may be involved in immune modulation, regulating the repertoire of genes expressed in the immune system’s cells. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.

Background: Physiotherapy and chronic low back pain (CLBP) form a broad and fast developing research area. The aim of the article was to holistically, thematically and chronologically analyze and synthesise literature production and identify most prolific research entities and research themes. Methods: The article quantitatively and quantitatively analyzed research literature production harvested from the Scopus bibliometric database. using a triangulation of bibliometric and thematic analysis. For this, Excell and VOSwiever software were used. Results: In the Scopus database, 2843 data sources were found, which were published between 1974 and February 26, 2024. The growth trend has been linearly positive since the beginning of publication, and after 2018, exponential growth began. A review of the most prolific entities showed that the most literature was published in America, Europe and Australasia. The thematic analysis of the information sources identified six main themes, while the chronological analysis revealed three main areas of developments: assessment tools, CLBP processing and study methodology. Conclusions: The results of the bibliometric study presents a good starting point for further research providing Taxonomy and research landscapes as a holistic framework offering multidisciplinary knowledge about CLBP, while chronological analysis provides a basis for identifying prospective research trends.

There has recently been interest in the development of small-molecule inhibitors of the oligomerization of Bacillus anthracis protective antigen for therapeutic use. Some of the proposed lead compounds have, however, unfavorable solubility in aqueous medium, which prevents their clinical use. In this computational work, we have designed several hundreds of derivatives with progressively higher hydrosolubility and tested their ability to dock the relevant binding cavity. The highest-ranking docking hits were then subjected to 125 ns-long simulations to ascertain the stability of the binding modes. Several of the potential candidates performed quite disappointingly , but two molecules showed very stable binding modes throughout the complete simulations. Besides the identification of these two promising leads, these molecular dynamics simulations allowed the discovery of several insights that shall prove useful in the further improvement of these candidate towards higher potency and stability.

The objective of this study was to evaluate the genetic effects involved on pepper fruit post-harvest water loss, and correlated to morphology traits. Fruits of eight landraces of C. baccatum, and their 28 hybrids, were evaluated in a randomized complete block design. Analysis of variance, diallel analysis, phenotypic and genotypic correlation were performed to compare fruit water loss (WL), width (FW), length (FL), total soluble solids (TSS), dry matter content (DMC), pericarp thickness (PT), cuticle thickness (CT), and exocarp thickness (ET). WL varied from 14 to 68% during storage. Non-additive effects played more important role than additive, including CT, EP and TSS. Effective strategies to reduce WL should be achieved by repeated backcrosses followed by selection in segregating populations (SP). Therefore, the selection of hybrids should follow high specific combining ability traits. Selecting fruits with higher CT and lower TSS values are indirectly selecting fruits with lower WL. Varieties with low WL can be breed using landraces 04 and 58 as parents or by the hybrid 04 x 44 in open lines in SP. Brazilian C. baccatum landraces are a source of genetic variability, and the SP emerging from crossing lines with reduced WL should develop new ways for conventional breeding.

Sleep is of vital necessity for health, it has a restorative and protective function for children and adolescents with chronic conditions and their families. The purpose was to identify the scientific production on sleep patterns in children and adolescents with chronic conditions and their families. This integrative review was developed in March and June 2022, of the MEDLINE, Web of Science, CINAHL and PSYCInfo. The articles included were original papers published be-tween January 2007 and mid-2022. Excluded were review studies that did not evaluate sleep and whose participants did not have chronic conditions or were not children, adolescents and/or their families. The searches returned 814 abstracts. After exclusions, 47 studies were selected to be read in full; of these, 29 were selected and were grouped empirically into four categories: major alterations in sleep patterns of children and adolescents with chronic conditions; the relationship between sleep disorders and symptoms in children and adolescents with chronic conditions; impaired sleep patterns of families of children and adolescents with chronic conditions; sleep alterations and their relationship with other problems in families of children and adolescents with chronic conditions. All studies showed sleep pattern impairment in children and adolescents with chronic conditions and their families.

Recent deep learning frameworks draw a strong research interest in the application of ego-motion estimation as they demonstrate a superior result compared to geometric approaches. However, due to the lack of multimodal datasets, most of these studies primarily focused on a single sensor-based estimation. To overcome this challenge, we collect a unique multimodal dataset named LboroAV2, using multiple sensors including camera, Light Detecting And Ranging (LiDAR), ultrasound, e-compass and rotary encoder. We also propose an end-to-end deep learning architecture for fusion of RGB images and LiDAR laser scan data for odometry application. The proposed method contains a convolutional encoder, a compressed representation and a recurrent neural network. Besides feature extraction and outlier rejection, the convolutional encoder produces a compressed representation which is used to visualise the network's learning process and to pass useful sequential information. The recurrent neural network uses this compressed sequential data to learn the relation between consecutive time steps. We use the LboroAV2 and KITTI VO datasets to experiment and evaluate our results. In addition to visualising the network's learning process, our approach gives superior results compared to other similar methods. The code for the proposed architecture is released in GitHub and accessible publicly.

Barley straw was used to reinforce PHB in a discontinuous semi-industrial process. Four different fibres were used as reinforcing material : sawdust (SW), defibred (DFBF), delignified (DBF) and bleached (BBF) fibres. Looking at the mechanical properties, onlythe elastic moduli (Et) revealed an improvement. Oppositely, the strengths at break, under both tensile and bending assays, tended to decrease, evidencing a poor affinity between both components. Thanks to the mechani-cal treatment applied on the fibre, DFBF appeared as the most promising filler with the mechani-cal properties of the composites closest to those of neat PHB. DFBF-based composites were then produced by means of a process intensification using a twin-screw extruder, and then moulded into flowerpots. Mechanical results showed almost the same properties between the discontinuous and intensification processes. The suitability of the material to be used on agriculture flowerpots was demonstrated by simulation. . PHB-DFBF composite material can be considered an alterna-tive to replace petrol-based products for applications in agriculture and horticulture.

Understanding the motor patterns underlying the movement of people with Parkinson's disease (PD) is fundamental to the effective targeting of non-pharmacological therapies. This study aims to analyze the gait pattern in relation to the evolutionary stage between I-II and III-IV according to the Hoehn and Yahr scale (H&amp;Y) in people affected by PD. The study was conducted with the participation of 37 PD patients, with a mean age of 70.09±9.53 years, and of whom 48.64% were women. The inclusion criteria were: 1. To be diagnosed with PD; 2. To be in an evolutionary stage of the disease of between I and IV and; 3. To be able to walk independently and without any assistance. Kinematic and spatial-temporal parameters of the gait were analyzed. The results show differences in speed of movement, cadence, stride length, support duration, swing duration, step width, walking cycle duration and double support time between the stages analyzed. These results confirm the differences in PD gait pattern between stages I-II and III-IV. Different behaviors of the same variable were recorded depending on whether the right or left sides were affected by PD.

Cambodia is a predominantly agrarian society, with a majority of the population residing in rural areas and relying on agriculture for food and income. The primary sources of food for the Khmer society are rice and fish. However, the country faces vulnerabilities due to climate change, natural disasters, impacts of hydropower and infrastructure development, and land grabs, which disrupt food sources and the livelihoods of local communities. Since 2015, the Royal Government of Cambodia (RGC) has been actively promoting rice production for export, resulting in increased rice farming seasons and annual rice production. Despite these efforts, a significant portion of the population still experiences food insecurity. Therefore, this study aims to explore the reasons why food security issues persist despite the government program to increase rice production. The study involves a review of existing literature and an examination of food security in three provinces in the Cambodian Mekong Delta. It concludes that, on the one hand, the increased rice production has increased food availability, but access to and utilization of food have been challenged by indebtedness, increased cost of production and migration, and on the other hand, the rights to foods have been challenged by land crabs, water conflicts, and lack of sectoral integrations of food systems; and compounded by climate change and environmental degradation, which all contribute to food security.

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

Background: The purpose of this review is to clarify the natural course of Benign Paroxysmal Torticollis (BPT) and to update the relationship of this disorder with migraine. BPT belongs to a group of “episodic syndromes that may be associated with migraine” and is diagnosed when according to diagnostic criteria of the International Classification of Headache Disorders, 3rd edition. It is present in infants and young children and it is an underdiagnosed manifestation, because it is not well recognized and in most cases with a benign evolution, but requires careful differential diagnosis. It was first described by Snyder in 1969 as a movement disorder, a cervical dystonia consequent to labyrinthic disorder.Materials and methods: The PubMed and Web of Science databases were consulted from 1968 to 2024, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines ,2020.( PRISMA)Results: 113 articles were identified, 86 selected and 20 considered for the purpose of this review. The clinical studies were considered in relation to evolution, cognitive and motor development, to genetic and not genetic etiology, to the relationship with migraine with and without aura, vestibular migraine, hemiplegic migraine, and paroxysmal vertigo.

The hazard and the carcinogenic risks due to the exposure to some potentially toxic elements by the Santiago Island (Cape Verde) population where calculated, considering soil ingestion, inhalation and dermal contact as exposure pathways. The topsoil of Santiago Island is enriched in Co, Cr, Cu, Ni, V, Zn, Mn and Cd to upper crust values. Hazard indices (HI) were calculated for these metals and As exposures, of Santiago Island population and the calculations were performed for children and adults. For children HI are higher than 1 for Co, Cr and Mn. So there is indication of potential non-carcinogenic risk for children, due to the high Co (HI=2.995), Cr (HI=1.329) and Mn (HI=1.126), values in soils. For the other elements and for adults there is no potential non-carcinogenic risk. Cancer risk was calculated for As, Cd, Cr and Ni exposures, for adults and children and the results are always lower than the carcinogenic target risk of 1x10-6, for As, Cd, and Ni. However, cancer risk are higher than the carcinogenic target risk for Cr, for adults. Regarding As, for children the fraction due to Riskingestion represents 51.6%, while Riskinhalation represents 48.0% and Riskdermalcontact represents only 0.4% of total risk. For adults Riskinhalation represents 81.3%, Riskingestion represents 16.6% and Riskdermal contact represents 2.1%. These results reflect the higher daily ingestion dose for children and the higher inhalation rate and higher dermal contact surface for adults. For the other elements and for adults the cancer risk due to Cr, Ni and Cd inhalation is always higher than for children, reflecting the higher inhalation rate for adults.

Invasive macrophytes are considered problematic in natural environments and hydroelectric reservoirs. Climate changes, the occurrence of watercourses, and biotic interactions influence the biological invasion of macrophytes. Native species can correlate with invasives positively or negatively. Urochloa subquadripara is an invasive in natural or disturbed habitats co-occurring with the natives Eichhornia crassipes and Salvinia minima. Aquatic plant communities can be altered by climate change, so species distribution models (SDMs) are important tools for predicting in-vaded areas. This work aimed to make an SDM for U. subquadripara correlating with the poten-tial distribution of native species E. crassipes and S. minima. Occurrence data for U. subquadripara, E. crassipes, and S. minima were collected from databases and in consultation with the published literature. Parameters encompassing biological information of the species were entered into the CLIMEX software and used to generate the Ecoclimatic Index (EI). The species co-occurrence was performed based on multicriteria decision-making (MCDM), and weights were assigned using the analytical hierarchy process (AHP). It was observed that U. subquadripara, E. crassipes, and S. minima have a higher occurrence in tropical and subtropical regions; however, it is predicted that, from climatic changes, these species may move to high latitudes. According to climate change, the risk of invasion by U. subquadripara in the northern hemisphere is mainly in lakes, while in the southern hemisphere, the areas conducive to invasions are rivers and reservoirs. In general, emerging and floating macrophyte species such as U. subquadripara, E. crassipes, and S. minima will be favored, causing suppression of submerged species. Therefore, identifying the potential distribution of these species allows the creation of pre-invasion intervention strategies.

Thermal comfort is extremely important in architecture, especially in environments with more people spending longer on studies or intellectual activities. This research describes a case study to investigate university buildings' energy and thermal performance as a part of the ANEEL program. Due to this importance, and the need to save energy in Brazilian public buildings, the ANEEL-the Brazilian Energy Electricity Regulatory Agency, launched 2016 a national program focusing on energy efficiency in public universities around the country. University offices and classrooms require high intellectual effort; thus, environmental comfort is critical for maintaining its users' physical and mental health. This study included a pre-diagnosis of the performance of the envelope, lighting, and air conditioning systems and a survey about the quality of the environments from the users' point of view. The Prescriptive Method of the Brazilian Labeling Program (PBE) for Commercial, Service, and Public Buildings (RTQ-C) assessed the building performance. Statistical analysis was applied to correlate the quality and thermal preference of the users from the PMV/PPD. The results showed a high rate of thermal discomfort in both environments of the studies, even when using air conditioning.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

Identifying ambient noise-based (ANb) signatures of streams can help in the estimation of their erosive potential (EP) that promotes reverie landslides and soil losses in the fluvial valleys. This is particularly imperative on flooding or rainy days, leading to stronger erosion-prone conditions (colluvium and boulders) of the valley beds inferred from georadar attribute analysis. Developing such research direction can benefit the local communities, as is the case with the Cerrado region of Brazil, where these phenomena have high destructive potential with social, economic, and climatic implications. For the present study, a seasonal stream in the Federal District of Brazil was investigated by ANb monitoring supported by Ground Penetration Radar (GPR) for site characterization. The ANb monitoring was conducted (at a safe distance) with a seismometer over several durations of dry and rainy conditions. The power spectral density (PSDs) was computed as a function of several variables, including weather conditions (rainfall, wind speed, and pressure), time-frequency spectrograms, and ambient noise displacement root mean square (RMS). This analysis also considered the single station horizontal-to-vertical spectral ratio (HVSR), where rain, wind, pressure, river flow and anthropogenic signatures were evident (at selective frequency ranges). Multi-peaks that emerged on the HVSR curve were further analyzed to identify amplitude and frequency changes, and the three peaks shift on average to a lower position during the rainy period. The GPR amplitude and waveform variation features were attributed to the stratigraphy (i.e., the boundary between valid and invalid regions and coherence value) of the floodplain and regions susceptible to erosion (erosion-prone lithological spots). This approach provides the basis for non-destructive monitoring tools enabling the detection of 'seismic signatures' and weak spots of the fluvial channels for improving environmental management.

Airborne wind energy (AWE) systems use tethered flying devices to harvest higher-altitude winds to produce electricity. For a successful deployment of these systems, it is crucial to understand how the public perceives them. If public concerns about the technology are not taken seriously, implementation could be delayed or, in some cases, prevented, resulting in increased costs for project developers and a lower contribution of the sector to renewable energy targets. This literature review assessed the current state of knowledge on public responses to AWE. An exhaustive literature search led to the identification of 40 relevant publications that were reviewed. The literature assumed that the safety, visibility, acoustic emissions, ecological impacts, and the siting of AWE systems shape public responses to the technology. The reviewed literature views people’s responses to AWE very optimistically but lacks scientific evidence to back up its claims. It seems to overlook that the influence of AWE’s characteristics (e.g., visibility) on public responses will also depend on a range of situational and psychological factors (e.g., people’s general attitude towards AWE, the public’s trust in project developers). Therefore, empirical social scientific research is needed to increase the field’s understanding of public responses to AWE and thereby facilitate deployment.

In response to droughts, various media campaigns and water saving instructions are released, often however, with only temporary water conservation effects. A promising development is this regard are Digital Water Meters (DWM) that provide near real-time water-use feedback. Despite extensive DWM experience in some water-stressed regions, a profound understanding of the initial attitude towards DWM and message tailoring opportunities are rarely empirically explored. Therefore, we aim to obtain insights into the attitude towards the introduction of DWM and explore opportunities for message tailoring, a topic of extra relevance as we may be on the threshold of a large-scale implementation in many world regions. Messages tailored to (i) normative beliefs and attitudes on drinking water, (ii) water-use activity and (iii) phase of decision-making, seem particularly compatible with DWM. Through a survey (n=1037) in the Netherlands, we observe that 93% of respondents have no objections utility investments in DWM and that 78% would accept a free DWM because of improved leakage detection, lower costs and environmental considerations. Finally, instead of sociodemographic factors, we observed that an attitude-based customer segmentation approach proved an especially useful predictor of respondent’s motivation to endorse DWM and forms a promising basis for water conservation message-tailoring strategies.

As part of a project ordered by the Ministry of Science, Technology and Innovation of Brazil, an assessment of Brazilian biological collections was conducted by the Brazilian Societies of Botany, Microbiology, Virology and Zoology to obtain data on the current state of these collections. The goal was to provide subsidies for future public policies, including financial support and prioritization policies. Herein, we present the results of the microbiological collections, which play a fundamental role in the ex situ conservation of biodiversity and support research, development and innovation. A survey was sent to public and private institutions in Brazil and answered by 168 microbiological collections from 79 different institutions. Among these, 73 comprise public research institutions and universities, demonstrating the State's importance in preserving and safeguarding Brazilian microbial diversity. The main taxonomic groups are bacteria (present in 70.24% of the collections) and fungi (52.98% of the collections) from different Brazilian ecosystems and biomes, including several type strains. Furthermore, the collections preserve microorganisms with biotechnological potential for application in environmental protection, public health, industry, and agribusiness. However, despite all these economic and biotechnological potentials, the data analysis showed serious limitations and fragilities, especially regarding physical infrastructure and human resources, and raises alerts about the risk that Brazilian collections are subjected to.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. The compounds were subjected to screening against L. amazonensis promastigotes, and their cytotoxicity was assessed in NIH/3T3 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes while demonstrating reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM, 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in NIH/3T3 cells (CC50 &gt; 200 µM). Although these results are promising, additional investigations focusing on intracellular amastigotes are required to determine the antileishmanial activity of the compounds. In conclusion, the identified selenium-containing compounds hold considerable potential as antileishmanial drug candidates and warrant further exploration in subsequent studies. These findings represent a significant step towards the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

Objectives: This study aimed to assess the impact of a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis from a single center between 2015 to 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features and Gleason score (GS). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. using the Kaplan-Meier survival function and Cox regression model were assessed. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after curative prostatectomy were 5%, 13%, and 21%, respectively. The survival analysis showed that adverse MRI features as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GS≥8, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE- and GS &lt;(4+4)) the presence of adverse MRI features, has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision-making; mECE+, TCCL, capsular disruption, and GS≥8 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who would benefit from closer monitoring.

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

The topography and chemical composition modification of the titanium (Ti) implants play a decisive role in improving biocompatibility and bioactivity, accelerating osseointegration, and, thus, determining clinical success. In spite of the development of surface modification strategies, bacterial contamination is a common cause of failure. The use of systemic antibiotic therapy does not guarantee action at the contaminated site. In this work, we proposed a surface treatment for Ti implant that aim to improve its osseointegration and reduce bacterial colonization in surgery site due to local release of antibiotic. The Ti disks were hydrothermally treated with 3M NaOH solution to form a nanostructured layer of titanate on the Ti surface. Metronidazole was impregnated on these nanostructured surfaces to allow its local release. The samples were coated with poly(vinyl alcohol) - PVA films with different thickness to evaluate a possible control of drug release. Gamma irradiation was used to crosslink the polymer chains leading to a hydrogel layer formation and to sterilize the samples. The samples were characterized by XRD, SEM, FTIR, contact angle measurements, “in vitro” bioactivity, and drug release analysis. The alkaline hydrothermal treatment successfully produced intertwined, web-like nanostructures on the Ti surface, providing wettability and bioactivity to Ti samples (Ti+TTNT samples). Metronidazole was successfully loaded and released from Ti+TTNT samples coated or not with PVA. Although the polymeric film acted as a physical barrier to drug delivery, all groups reached the minimum inhibitory concentration for anaerobic bacteria. Thus, the surface modification method presented is a potential approach to improve the osseointegration of the Ti implant and to associate local drug delivery to dental implants, preventing early infections and bone failure.

During embryo development, the endoplasmic reticulum (ER) acts as an important site for protein biosynthesis, however, in vitro culture (IVC) can negatively affect ER homeostasis. Thereby, the aim of our study was to evaluate the effects of supplementation of tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, in the IVC of bovine embryos. Two experiments were carried out: Exp. 1: evaluation of blastocyst rate, hatching kinetics and gene expression of hatched embryos after being treated with different concentrations of TUDCA (50, 200 or 1,000 μM) in the IVC; Exp. 2: evaluation of the re-expansion, hatching, and gene expression of hatched embryos previously treated with 200 µM of TUDCA at IVC and submitted to vitrification. There was no increase in the blastocyst and hatched blastocyst rates treated with TUDCA in the IVC. However, embryos submitted to vitrification after treatment with 200 µM of TUDCA, increased hatching rate post-warming, together with a down-regulation in the expression of ER stress-related genes and the accumulation of lipids. In conclusion, this work showed that the addition of TUDCA during in vitro culture can improve the cryotolerance of the bovine blastocyst through the putative modulation of ER and oxidative stress.