Enhancing Lung Recellularization with Mesenchymal Stem Cells via Photobiomodulation Therapy: Insights into Cytokine Modulation and Sterilization.

Several lung diseases can cause structural damage, making lung transplantation the only therapeutic option for advanced disease stages. However, the transplantation success rate remains limited. Lung bioengineering using the natural extracellular matrix (ECM) of decellularized lungs is a potential alternative. The use of undifferentiated cells to seed the ECM is practical; however, sterilizing the organ for recellularization is challenging. Photobiomodulation therapy (PBMT) may offer a solution, in which the wavelength is crucial for tissue penetration. This study aimed to explore the potential of optimizing lung recellularization with mesenchymal stem cells using PBMT (660 nm) after sterilization with PBMT (880 nm). The lungs from C57BL/6 mice were decellularized using 1% SDS and sterilized using PBMT (880 nm, 100 mW, 30 s). Recellularization was performed in two groups: (1) recellularized lung and (2) recellularized lung + 660 nm PBMT (660 nm, 100 mW, 30 s). Both were seeded with mesenchymal stem cells from human tooth pulp (DPSc) and incubated for 24 h at 37 °C and 5% CO2 in bioreactor-like conditions with continuous positive airway pressure (CPAP) at 20 cmH2O and 90% O2. The culture medium was analyzed after 24 h. H&E, immunostaining, SEM, and ELISA assays were performed. Viable biological scaffolds were produced, which were free of cell DNA and preserved the glycosaminoglycans; collagens I, III, and IV; fibronectin; laminin; elastin; and the lung structure (SEM). The IL-6 and IL-8 levels were stable during the 24 h culture, but the IFN-γ levels showed significant differences in the recellularized lung and recellularized lung + 660 nm PBMT groups. Greater immunological modulation was observed in the recellularized groups regarding pro-inflammatory cytokines (IL-6, IFN-γ, and IL-8). These findings suggest that PBMT plays a role in cytokine regulation and antimicrobial activity, thus offering promise for enhanced therapeutic strategies in lung bioengineering.

Rare genetic variants of NLRP12 in Admixed Latino-American Children with SARS-CoV-2-related Multisystem Inflammatory Syndrome.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole-exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.

Visual experience reduces the spatial redundancy between cortical feedback inputs and primary visual cortex neurons.

The role of experience in the organization of cortical feedback (FB) remains unknown. We measured the effects of manipulating visual experience on the retinotopic specificity of supragranular and infragranular projections from the lateromedial (LM) visual area to layer (L)1 of the mouse primary visual cortex (V1). LM inputs were, on average, retinotopically matched with V1 neurons in normally and dark-reared mice, but visual exposure reduced the fraction of spatially overlapping inputs to V1. FB inputs from L5 conveyed more surround information to V1 than those from L2/3. The organization of LM inputs from L5 depended on their orientation preference and was disrupted by dark rearing. These observations were recapitulated by a model where visual experience minimizes receptive field overlap between LM inputs and V1 neurons. Our results provide a mechanism for the dependency of surround modulations on visual experience and suggest how expected interarea coactivation patterns are learned in cortical circuits.

Correction: Borges et al. The Roles of Potassium and Calcium Currents in the Bistable Firing Transition. Brain Sci. 2023, 13, 1347.

Funding Updated [...].

Extracellular matrix of lung scaffolds submitted to different means of sterilization: a systematic review.

Chronic respiratory diseases often necessitate lung transplantation due to irreversible damage. Organ engineering offers hope through stem cell-based organ generation. However, the crucial sterilization step in scaffold preparation poses challenges. This study conducted a systematic review of studies that analysed the extracellular matrix (ECM) conditions of decellularised lungs subjected to different sterilisation processes. A search was performed for articles published in the PubMed, Web of Sciences, Scopus, and SciELO databases according to the PRISMA guidelines. Overall, five articles that presented positive results regarding the effectiveness of the sterilisation process were selected, some of which identified functional damage in the ECM. Was possible concluded that regardless of the type of agent used, physical or chemical, all of them demonstrated that sterilisation somehow harms the ECM. An ideal protocol has not been found to be fully effective in the sterilisation of pulmonary scaffolds for use in tissue and/or organ engineering.

Estrogenic Responsiveness of Brown Trout Primary Hepatocyte Spheroids to Environmental Levels of 17α-Ethinylestradiol.

Three-dimensional (3D) fish hepatocyte cultures are promising alternative models for replicating in vivo data. Few studies have attempted to characterise the structure and function of fish 3D liver models and illustrate their applicability. This study aimed to further characterise a previously established spheroid model obtained from juvenile brown trout (Salmo trutta) primary hepatocytes under estrogenic stimulation. The spheroids were exposed for six days to environmentally relevant concentrations of 17α-ethinylestradiol-EE2 (1-100 ng/L). The mRNA levels of peroxisome (catalase-Cat and urate oxidase-Uox), lipid metabolism (acyl-CoA long chain synthetase 1-Acsl1, apolipoprotein AI-ApoAI, and fatty acid binding protein 1-Fabp1), and estrogen-related (estrogen receptor α-ERα, estrogen receptor ß-ERß, vitellogenin A-VtgA, zona pellucida glycoprotein 2.5-ZP2.5, and zona pellucida glycoprotein 3a.2-ZP3a.2) target genes were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemistry was used to assess Vtg and ZP protein expressions. At the highest EE2 concentration, VtgA and ZP2.5 genes were significantly upregulated. The remaining target genes were not significantly altered by EE2. Vtg and ZP immunostaining was consistently increased in spheroids exposed to 50 and 100 ng/L of EE2, whereas lower EE2 levels resulted in a weaker signal. EE2 did not induce significant changes in the spheroids' viability and morphological parameters. This study identified EE2 effects at environmentally relevant doses in trout liver spheroids, indicating its usefulness as a proxy for in vivo impacts of xenoestrogens.

Clinical guidelines for herpes labialis: recommendations and quality evaluation according to AGREE II.

Cold sores require Healthcare professionals to employ specific approaches for prevention and management, with the need for effective therapeutic guidelines and ongoing improvement in patient care. AIM: To evalúate the methodological quality of Clinical Guidelines (CG), clinical guides and manuals for care of the population affected by herpes labialis, to verify their compliance with evidence-based health standards. MATERIALS AND METHOD: A search was conducted for CG on labial herpes in the MedicalLiteratureAnalysis andRetrieval System Online (Medline) database, Google Scholar, Brazilian Virtual Health Library (BVS), and sites of institutions/professional categories, using the descriptors "herpes labialis" or "oral herpes". Document quality was assessed using the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II). The Kappa test was used to avoid randomness or poor agreement between results. RESULTS: Analysis of the 12 selected publications on the management of labial herpes revealed flaws in quality, as the publications did not follow a quality standard. The main quality flaws identified were in "rigor in development" and "applicability. ". CONCLUSIONS: Priorities need to be redefined in the development of CG for clinical practice related to fever blisters to reduce the variability of the quality standard, and generate reliable, applicable recommendations.

A Herpes labial requer dos profissionais abordagens específicas para prevenido e manejo, com a ne-cessidade de diretrizes terapéuticas eficazes e continuo aprimoramento do cuidado ao paciente. OBJETIVO: avaliar a qualidade metodológica de documentos que abordaram Diretrizes Clínicas (DC), guias clínicos e manuais para o cuidado da populando afetada pelo herpes labial, verificando sua conformidade com padroes de saúde baseados em evidencias. MATERIAIS E MÉTODO: As DC sobre herpes labial foram pesquisadas na base de dados Medical Literature Analysis and Retrieval System Online (Medline), Google Académico, Biblioteca Virtual em Saúde (BVS) e em sites de instituigoes/categorias profissionais, utilizando os descritores "herpes labial" ou "herpes oral". Utilizamos aferramenta The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) para a avaliagdo da qualidade. O teste Kappa também foi utilizado para evitar aleatoriedade ou baixa concordáncia entre os resultados. RESULTADOS: Na análise das 12 publicagoes selecionadas sobre o manejo do herpes labial, foram identificadas falhas na qualidade dos documentos, que ndo seguiram um padrdo de qualidade. As principais falhas de qualidade identificadas foram em "rigor no desenvolvimento" e "aplicabilida-de". CONCLUSÃO: é necessário um reenfoque para definir prioridades no desenvolvimento de DC para a prática clínica do herpes labial, a fim de reduzir a variabilidade do padrdo de qualidade e gerar recomendagoes que possam ser confiáveis e aplicáveis.

Tag SNP selection for prediction of adaptation traits in Braford and Hereford cattle using Bayesian methods.

This study utilized Bayesian inference in a genome-wide association study (GWAS) to identify genetic markers associated with traits relevant to the adaptation of Hereford and Braford cattle breeds. We focused on eye pigmentation (EP), weaning hair coat (WHC), yearling hair coat (YHC), and breeding standard (BS). Our dataset comprised 126,290 animals in the pedigree. Out of these, 233 sires were genotyped using high-density (HD) chips, and 3750 animals with medium-density (50 K) single-nucleotide polymorphism (SNP) chips. Employing the Bayes B method with a prior probability of π = 0.99, we identified and tagged single nucleotide polymorphisms (Tag SNPs), ranging from 18 to 117 SNPs depending on the trait. These Tag SNPs facilitated the construction of reduced SNP panels. We then evaluated the predictive accuracy of these panels in comparison to traditional medium-density SNP chips. The accuracy of genomic predictions using these reduced panels varied significantly depending on the clustering method, ranging from 0.13 to 0.65. Additionally, we conducted functional enrichment analysis that found genes associated with the most informative SNP markers in the current study, thereby providing biological insights into the genomic basis of these traits.

Influence of Silver Nanoparticles on the Metabolites of Two Transgenic Soybean Varieties: An NMR-Based Metabolomics Approach.

This study investigated the effect of AgNPs and AgNO3, at concentrations equivalent, on the production of primary and secondary metabolites on transgenic soybean plants through an NMR-based metabolomics. The plants were cultivated in a germination chamber following three different treatments: T0 (addition of water), T1 (addition of AgNPs), and T2 (addition of AgNO3). Physiological characteristics, anatomical analyses through microscopic structures, and metabolic profile studies were carried out to establish the effect of abiotic stress on these parameters in soybean plants. Analysis of the 1H NMR spectra revealed the presence of amino acids, organic acids, sugars, and polyphenols. The metabolic profiles of plants with AgNP and AgNO3 were qualitatively similar to the metabolic profile of the control group, suggesting that the application of silver does not affect secondary metabolites. From the PCA, it was possible to differentiate the three treatments applied, mainly based on the content of fatty acids, pinitol, choline, and betaine.

Identifying Effective Connectivity between Stochastic Neurons with Variable-Length Memory Using a Transfer Entropy Rate Estimator.

Information theory explains how systems encode and transmit information. This article examines the neuronal system, which processes information via neurons that react to stimuli and transmit electrical signals. Specifically, we focus on transfer entropy to measure the flow of information between sequences and explore its use in determining effective neuronal connectivity. We analyze the causal relationships between two discrete time series, X:=Xt:t∈Z and Y:=Yt:t∈Z, which take values in binary alphabets. When the bivariate process (X,Y) is a jointly stationary ergodic variable-length Markov chain with memory no larger than k, we demonstrate that the null hypothesis of the test-no causal influence-requires a zero transfer entropy rate. The plug-in estimator for this function is identified with the test statistic of the log-likelihood ratios. Since under the null hypothesis, this estimator follows an asymptotic chi-squared distribution, it facilitates the calculation of p-values when applied to empirical data. The efficacy of the hypothesis test is illustrated with data simulated from a neuronal network model, characterized by stochastic neurons with variable-length memory. The test results identify biologically relevant information, validating the underlying theory and highlighting the applicability of the method in understanding effective connectivity between neurons.

Don't Let the Sun Rise on Small Bowel Obstruction Without Surgical Consultation-Redefining Nonoperative Management Pathways.

Introduction: Small bowel obstruction (SBO) is a common cause of hospital admission leading to resource utilization. The majority of these patients require non-operative management (NOM) which can lead to increased length of stay (LOS), readmissions, resource utilization, and throughput delays. Early surgical consultation (SC) for SBO may improve efficiency and outcomes. Methods: We implemented an institution-wide intervention (INT) to encourage early SC (<1 day of diagnosis) for SBO patients in July 2022. A retrospective analysis was performed on all patients with SBO requiring NOM from January 2021 to June 2023, categorized into pre- and post-INT groups. The primary outcome was the number of SC's and secondary outcomes were early SC (<1 day of diagnosis), utilization of SBFT, LOS, 30-day readmission, and costs of admission. Results: A total of 670 patients were included, 438 in the pre-INT and 232 in the post-INT group. Overall, SBFT utilization was significantly higher in cases with SC (17.2% vs 41.4%, P < .001). Post-INT patients were more likely to receive SC (94.0% vs 83.3%, P < .001) and increased SBFT utilization (47.0% vs 33.6%, P = .001). Additionally, early SC improved significantly in the post-INT group (74.3% vs 65.7%, P = .03). There was no difference in LOS between groups (4.0 vs 3.8 days, P = .48). There was a trend toward decreased readmission rates in the INT group at 30 days (7.3% vs 11.0%, P = .13) and reduced direct costs in the INT group (US$/admission = 8467 vs 8708, P = .1). Conclusion: Hospital-wide interventions to increase early surgical involvement proved effective by improving early SC, increased SBFT utilization, and showed a trend towards decreased readmission rates and direct costs.

Seeing further into the early steps of the endangered atlantic goliath grouper (Epinephelus itajara): Eye lenses high resolution isotopic profiles reveal ontogenetic trophic and habitat shifts.

Estuarine mangroves are often considered nurseries for the Atlantic Goliath grouper juveniles. Yet, the contributions of different estuarine primary producers and habitats as sources of organic matter during early ontogenetic development remain unclear. Given the species' critically endangered status and protection in Brazil, obtaining biological samples from recently settled recruits in estuaries is challenging. In this study, we leveraged a local partnership with fishers and used stable isotope (C and N) profiles from the eye lenses of stranded individuals or incidentally caught by fishery to reconstruct the trophic and habitat changes of small juveniles. The eye lens grows by the apposition of protein-rich layers. Once these layers are formed, they become inert, allowing to make inferences on the trophic ecology and habitat use along the development of the individual until its capture. We used correlations between fish size and the entire eye lens size, along with estuarine baselines, to reconstruct the fish size and trophic positions for each of the lens layers obtained. We then used dominant primary producers and basal sources from mangrove sheltered, exposed estuarine and marine habitats to construct an ontogenetic model of trophic and habitat support changes since maternal origins. Our model revealed marine support before the juveniles reached 25 mm (standard length), followed by a rapid increase in reliance on mangrove sheltered sources, coinciding with the expected size at settlement. After reaching 60 mm, individuals began to show variability. Some remained primarily supported by the mangrove sheltered area, while others shifted to rely more on the exposed estuarine area around 150 mm. Our findings indicate that while mangroves are critical for settlement, as Goliath grouper juveniles grow, they can utilize organic matter produced throughout the estuary. This underscores the need for conservation strategies that focus on seascape connectivity, as protecting just one discrete habitat may not be sufficient to preserve this endangered species and safeguard its ecosystem functions.

Rootstocks affect the vulnerability to embolism and pit membrane thickness in Citrus scions.

Embolism resistance of xylem tissue varies among species and is an important trait related to drought resistance, with anatomical attributes like pit membrane thickness playing an important role in avoiding embolism spread. Grafted Citrus trees are commonly grown in orchards, with the rootstock being able to affect the drought resistance of the whole plant. Here, we evaluated how rootstocks affect the vulnerability to embolism resistance of the scion using several rootstock/scion combinations. Scions of 'Tahiti' acid lime, 'Hamlin', 'Pera' and 'Valencia' oranges grafted on a 'Rangpur' lime rootstock exhibit similar vulnerability to embolism. In field-grown trees, measurements of leaf water potential did not suggest significant embolism formation during the dry season, while stomata of Citrus trees presented an isohydric response to declining water availability. When 'Valencia' orange scions were grafted on 'Rangpur' lime, 'IAC 1710' citrandarin, 'Sunki Tropical' mandarin or 'Swingle' citrumelo rootstocks, variation in intervessel pit membrane thickness of the scion was found. The 'Rangpur' lime rootstock, which is known for its drought resistance, induced thicker pit membranes in the scion, resulting in higher embolism resistance than the other rootstocks. Similarly, the rootstock 'IAC 1710' citrandarin generated increased embolism resistance of the scion, which is highly relevant for citriculture.

The neurobiological effects of senescence on dopaminergic system: A comprehensive review.

Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.

Interaction of the antifungal ketoconazole and its diphenylphosphine derivatives with lipid bilayers: Insights into their antifungal action.

Ketoconazole (Ke) is an important antifungal drug, and two of its diphenylphosphinemethyl derivatives (KeP: Ph2PCH2-Ke and KeOP: Ph2P(O)CH2-Ke) have shown improved antifungal activity, namely against a yeast strain lacking ergosterol, suggesting alternative modes of action for azole compounds. In this context, the interactions of these compounds with a model of the cell membrane were investigated, using POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) large unilamellar vesicles and taking advantage of the intrinsic fluorescence of Ke, KeP and KeOP. Steady-state fluorescence spectra and anisotropy, including partition and aggregation studies, as well as fluorescence lifetime measurements, were carried out. In addition, the ability of the compounds to increase membrane permeability was assessed through carboxyfluorescein leakage. The membrane/water mole fraction partition coefficients (Kp,x): (3.31 ± 0.36) x105, (8.31 ± 1.60) x105 and (4.66 ± 0.72) x106, for Ke, KeP and KeOP, respectively, show that all three compounds have moderate to high affinity for the lipid bilayer. Moreover, KeP, and particularly KeOP interact more efficiently with POPC bilayers than Ke, which correlates well with their in vitro antifungal activity. Furthermore, although the three compounds disturb the lipid bilayer, KeOP is the quickest and most efficient one. Hence, the higher affinity and ability to permeabilize the membrane of KeOP when compared to that of KeP, despite the higher lipophilicity of the latter, points to an important role of Ph2P(O)CH2- oxygen. Overall, this work suggests that membrane interactions are important for the antifungal activity of these azoles and should be considered in the design of new therapeutic agents.

Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes. Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (EGFR) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.7%). Notably, anaplastic lymphoma kinase (ALK) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR, ALK, breast cancer (BRAF) gene, c-ros oncogene 1 (ROS1), and rearranged during transfection (RET) gene, in 32.3% of the patients. Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.

Discovery of new piperaquine hybrid analogs linked by triazolopyrimidine and pyrazolopyrimidine scaffolds with antiplasmodial and transmission blocking activities.

The World Health Organization (WHO) estimated that there were 247 million malaria cases in 2021 worldwide, representing an increase in 2 million cases compared to 2020. The urgent need for the development of new antimalarials is underscored by specific criteria, including the requirement of new modes of action that avoid cross-drug resistance, the ability to provide single-dose cures, and efficacy against both assexual and sexual blood stages. Motivated by the promising results obtained from our research group with [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives, we selected these molecular scaffolds as the foundation for designing two new series of piperaquine analogs as potential antimalarial candidates. The initial series of hybrids was designed by substituting one quinolinic ring of piperaquine with the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine nucleus. To connect the heterocyclic systems, spacers with 3, 4, or 7 methylene carbons were introduced at the 4 position of the quinoline. In the second series, we used piperazine as a spacer to link the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine group to the quinoline core, effectively merging both pharmacophoric groups via a rigid spacer. Our research efforts yielded promising compounds characterized by low cytotoxicity and selectivity indices exceeding 1570. These compounds displayed potent in vitro inhibitory activity in the low nanomolar range against the erythrocytic form of the parasite, encompassing both susceptible and resistant strains. Notably, these compounds did not show cross-resistance with either chloroquine or established P. falciparum inhibitors. Even though they share a pyrazolo- or triazolo-pyrimidine core, enzymatic inhibition assays revealed that these compounds had minimal inhibitory effects on PfDHODH, indicating a distinct mode of action unrelated to targeting this enzyme. We further assessed the compounds' potential to interfere with gametocyte and ookinete infectivity using mature P. falciparum gametocytes cultured in vitro. Four compounds demonstrated significant gametocyte inhibition ranging from 58 % to 86 %, suggesting potential transmission blocking activity. Finally, we evaluated the druggability of these new compounds using in silico methods, and the results indicated that these analogs had favorable physicochemical and ADME (absorption, distribution, metabolism, and excretion) properties. In summary, our research has successfully identified and characterized new piperaquine analogs based on [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine scaffolds and has demonstrated their potential as promising candidates for the development of antimalarial drugs with distinct mechanisms of action, considerable selectivity, and P. falciparum transmission blocking activity.

Clinical guidelines for herpes labialis: recommendations and quality evaluation according to AGREE II / Diretrizes clínicas para o herpes labial: recomendares e avalia$ao de qualidade de acordo com o AGREE II

ABSTRACT Cold sores require Healthcare professionals to employ specific approaches for prevention and management, with the need for effective therapeutic guidelines and ongoing improvement in patient care. Aim To evalúate the methodological quality of Clinical Guidelines (CG), clinical guides and manuals for care of the population affected by herpes labialis, to verify their compliance with evidence-based health standards. Materials and Method A search was conducted for CG on labial herpes in the MedicalLiteratureAnalysis andRetrieval System Online (Medline) database, Google Scholar, Brazilian Virtual Health Library (BVS), and sites of institutions/professional categories, using the descriptors "herpes labialis" or "oral herpes". Document quality was assessed using the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II). The Kappa test was used to avoid randomness or poor agreement between results. Results Analysis of the 12 selected publications on the management of labial herpes revealed flaws in quality, as the publications did not follow a quality standard. The main quality flaws identified were in "rigor in development" and "applicability. " Conclusions Priorities need to be redefined in the development of CG for clinical practice related to fever blisters to reduce the variability of the quality standard, and generate reliable, applicable recommendations.

RESUMO A Herpes labial requer dos profissionais abordagens específicas para prevenido e manejo, com a ne-cessidade de diretrizes terapéuticas eficazes e continuo aprimoramento do cuidado ao paciente. Objetivo avaliar a qualidade metodológica de documentos que abordaram Diretrizes Clínicas (DC), guias clínicos e manuais para o cuidado da populando afetada pelo herpes labial, verificando sua conformidade com padroes de saúde baseados em evidencias. Materiais e Método As DC sobre herpes labial foram pesquisadas na base de dados Medical Literature Analysis and Retrieval System Online (Medline), Google Académico, Biblioteca Virtual em Saúde (BVS) e em sites de instituigoes/categorias profissionais, utilizando os descritores "herpes labial" ou "herpes oral". Utilizamos aferramenta The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) para a avaliagdo da qualidade. O teste Kappa também foi utilizado para evitar aleatoriedade ou baixa concordáncia entre os resultados. Resultados Na análise das 12 publicagoes selecionadas sobre o manejo do herpes labial, foram identificadas falhas na qualidade dos documentos, que ndo seguiram um padrdo de qualidade. As principais falhas de qualidade identificadas foram em "rigor no desenvolvimento" e "aplicabilida-de". Conclusao é necessário um reenfoque para definir prioridades no desenvolvimento de DC para a prática clínica do herpes labial, a fim de reduzir a variabilidade do padrdo de qualidade e gerar recomendagoes que possam ser confiáveis e aplicáveis.

Reproduction of Meloidogyne morocciensis (Tylenchida: Meloidogynidae) in weeds found in Brazil.

Weeds can be hosts of root-knot nematodes of the genus Meloidogyne. The importance of the species Meloidogyne morocciensis parasitizing many crops is recognized, but their reproductive capacity in weeds is not known. The present study hypothesizes the ability of M. morocciensis to parasitize and reproduce in different weed species found in Brazil. The objective was to evaluate the reproduction of M. morocciensis in 36 weed species. The plants were individually inoculated with 5,000 eggs and second stage juveniles and kept in greenhouse for 60 days. The experimental design was completely randomized with twelve replications. The root system of each plant was evaluated for gall index (GI), final nematode population (PF), number of nematode/g of root (NNGR) and reproduction factor (RF). It was verified that M. morocciensis has the capacity to parasite 36 weed species belonging to 16 different botanical families, confirming the hypothesis proposed. From the 36 species evaluated, 77.8% (28) were susceptible (FR ≥ 1.0) to M. morocciensis. The present study is the first to identify different weeds as hosts of M. morocciensis, evidencing its polyphagous habit, indicating species of plants with high capacity to multiply this nematode and that need more attention during the integrated management of these pathogen.

From nuclear track characterization to machine learning based image classification in neutron autoradiography for boron neutron capture therapy.

Knowledge of the 10B microdistribution is of great relevance in BNCT studies. Since 10B concentration assesment through neutron autoradiography depends on the correct quantification of tracks in a nuclear track detector, image acquisition and processing conditions should be controlled and verified, in order to obtain accurate results to be applied in the frame of BNCT. With this aim, an image verification process was proposed, based on parameters extracted from the quantified nuclear tracks. Track characterization was performed by selecting a set of morphological and pixel-intensity uniformity parameters from the quantified objects (area, diameter, roundness, aspect ratio, heterogeneity and clumpiness). Their distributions were studied, leading to the observation of varying behaviours in images generated by different samples and acquisition conditions. The distributions corresponding to samples coming from the BNC reaction showed similar attributes in each analyzed parameter, proving to be robust to the experimental process, but sensitive to light and focus conditions. Considering those observations, a manual feature extraction was performed as a pre-processing step. A Support Vector Machine (SVM) and a fully dense Neural Network (NN) were optimized, trained, and tested. The final performance metrics were similar for both models: 93%-93% for the SVM, vs 94%-95% for the NN in accuracy and precision respectively. Based on the distribution of the predicted class probabilities, the latter had a better capacity to reject inadequate images, so the NN was selected to perform the image verification step prior to quantification. The trained NN was able to correctly classify the images regardless of their track density. The exhaustive characterization of the nuclear tracks provided new knowledge related to the autoradiographic images generation. The inclusion of machine learning in the analysis workflow proves to optimize the boron determination process and paves the way for further applications in the field of boron imaging.