Investigation of thallium as a contaminant in dietary supplements marketed for weight loss and physical fitness.

Dietary supplements are drastically growing as a category of consumer products all over the world. The abuse of supplements marketed for slimming purposes and physical fitness has been observed worldwide in recent years, which raises concerns in terms of public health. In this study, different types of dietary supplements marketed and delivered through the e-commerce were studied for the determination of thallium as a hazardous inorganic contaminant. The total content of thallium was determined by a sensitive voltammetric method after a microwave-assisted oxidative digestion of the sample. In addition, a comparative spectrometric method was applied for validation of the results in the samples. The maximum concentration found for thallium was found to be 2.89 mg kg-1, which well agree with the comparative measurement. Considering the 32 studied formulations, it can be pointed out that ∼24% of the of dietary supplements presented Tl concentrations at concentrations higher than 1 mg kg-1. The results permitted the assessment of the health risk related to thallium from contaminated samples, based on the calculation of the estimated daily intake (EDI) and the risk quotient (HQ). The highest daily intake of thallium was calculated as 82.0 µg day-1 in a protein-based supplement, which is equivalent to an EDI of 1.17 µg kg-1 day-1. This work highlights the need to develop regulations on the limits of toxic elements such as thallium in widely consumed dietary supplements, as well as an in-depth look at the adverse effects caused by this element in the human body.

Disentangling doping and strain effects at defects of grown MoS2 monolayers with nano-optical spectroscopy.

The role of defects in two-dimensional semiconductors and how they affect the intrinsic properties of these materials have been a widely researched topic over the past few decades. Optical characterization techniques such as photoluminescence and Raman spectroscopies are important tools to probe the physical properties of semiconductors and the impact of defects. However, confocal optical techniques present a spatial resolution limitation lying in a µm-scale, which can be overcome by the use of near-field optical measurements. Here, we use tip-enhanced photoluminescence and Raman spectroscopies to unveil the nanoscale optical properties of grown MoS2 monolayers, revealing that the impact of doping and strain can be disentangled by the combination of both techniques. A noticeable enhancement of the exciton peak intensity corresponding to trion emission quenching is observed at narrow regions down to a width of 47 nm at grain boundaries related to doping effects. Besides, localized strain fields inside the sample lead to non-uniformities in the intensity and energy position of photoluminescence peaks. Finally, two distinct MoS2 samples present different nano-optical responses at their edges associated with opposite strains. The edge of the first sample shows a photoluminescence intensity enhancement and energy blueshift corresponding to a frequency blueshift for E2g and 2LA Raman modes. In contrast, the other sample displays a photoluminescence energy redshift and frequency red shifts for E2g and 2LA Raman modes at their edges. Our work highlights the potential of combining tip-enhanced photoluminescence and Raman spectroscopies to probe localized strain fields and doping effects related to defects in two-dimensional materials.

Boring systematics: A genome skimmed phylogeny of ctenostome bryozoans and their endolithic family Penetrantiidae with the description of one new species.

Ctenostomes are a group of gymnolaemate bryozoans with an uncalcified chitinous body wall having few external, skeletal characters. Hence, species identification is challenging and their systematics remain poorly understood, even more so when they exhibit an endolithic (boring) lifestyle. Currently, there are four Recent families of endolithic bryozoans that live inside mineralized substrates like mollusk shells. In particular, Penetrantiidae Silén, 1946 has received considerable attention and its systematic affinity to either cheilostomes or ctenostomes has been debated. Species delimitation of penetrantiids remains difficult, owing to a high degree of colonial and zooidal plasticity. Consequently, an additional molecular approach is essential to unravel the systematics of penetrantiids, their phylogenetic placement and their species diversity. We therefore sequenced the mitochondrial (mt) genomes and two nuclear markers of 27 ctenostome species including nine penetrantiids. Our phylogeny supports the Penetrantiidae as a monophyletic group placed as sister taxon to the remaining ctenostomes alongside paludicellids, arachnidioids and terebriporids. The boring family Terebriporidae d'Orbigny, 1847 were previously considered to be among vesicularioids, but our results suggest an arachnidioid affinity instead. Ctenostome paraphyly is supported by our data, as the cheilostomes nest within them. A Multiporata clade is also well supported, including the former victorelloid genus Sundanella. Altogether, this study provides new insights into ctenostome systematics, assists with species delimitation and contributes to our understanding of the bryozoan tree of life.

Anabolic steroids and the evaluation of patients with acute PM tendon rupture using microscopy and MRI.

This study presented a pioneering investigation of the changes in the magnetic resonance imaging images of pectoralis major muscle (PMM) tendon rupture. In all, 26 men were evaluated with acute total PMM rupture (<3 months since injury) with a mean age of 37.3 years (SD = 9.7 years) and 10 control patients with a mean age of 32.6 years (SD = 4.2 years). The evaluation of the tendon PMM injuries was based on the magnetic resonance imaging exam and the histological analysis. The magnetic resonance imaging of the surgically showed two (7.1%) contralateral sides were normal, 16 (57.1%) showed superior tendinopathy, and 10 (35.7%) had total tendinopathy. Inferior tendinopathy was not observed. The tendon histology revealed degenerative changes in 16 (66.7%) fragments, with 12 (50.0%) considered as mild (<25%), and four considered as (16.7%) high (>50.0%) tendinopathy. Total acute rupture of the PMM tendon among weightlifters might be associated with tendinous degeneration prior to injury.

Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection.

Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs). Methods and results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. Conclusion: This work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.

Blocking the CTLA-4 and PD-1 pathways during pulmonary paracoccidioidomycosis improves immunity, reduces disease severity, and increases the survival of infected mice.

Immune checkpoint pathways, i.e., coinhibitory pathways expressed as feedback following immune activation, are crucial for controlling an excessive immune response. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) are the central classical checkpoint inhibitory (CPI) molecules used for the control of neoplasms and some infectious diseases, including some fungal infections. As the immunosuppression of severe paracoccidioidomycosis (PCM), a chronic granulomatous fungal disease, was shown to be associated with the expression of coinhibitory molecules, we hypothesized that the inhibition of CTLA-4 and PD-1 could have a beneficial effect on pulmonary PCM. To this end, C57BL/6 mice were infected with Paracoccidioides brasiliensis yeasts and treated with monoclonal antibodies (mAbs) α-CTLA-4, α-PD-1, control IgG, or PBS. We verified that blockade of CTLA-4 and PD-1 reduced the fungal load in the lungs and fungal dissemination to the liver and spleen and decreased the size of pulmonary lesions, resulting in increased survival of mice. Compared with PBS-treated infected mice, significantly increased levels of many pro- and anti-inflammatory cytokines were observed in the lungs of α-CTLA-4-treated mice, but a drastic reduction in the liver was observed following PD-1 blockade. In the lungs of α-CPI and IgG-treated mice, there were no changes in the frequency of inflammatory leukocytes, but a significant reduction in the total number of these cells was observed. Compared with PBS-treated controls, α-CPI- and IgG-treated mice exhibited reduced pulmonary infiltration of several myeloid cell subpopulations and decreased expression of costimulatory molecules. In addition, a decreased number of CD4+ and CD8+ T cells but sustained numbers of Th1, Th2, and Th17 T cells were detected. An expressive reduction in several Treg subpopulations and their maturation and suppressive molecules, in addition to reduced numbers of Treg, TCD4+, and TCD8+ cells expressing costimulatory and coinhibitory molecules of immunity, were also detected. The novel cellular and humoral profiles established in the lungs of α-CTLA-4 and α-PD-1-treated mice but not in control IgG-treated mice were more efficient at controlling fungal growth and dissemination without causing increased tissue pathology due to excessive inflammation. This is the first study demonstrating the efficacy of CPI blockade in the treatment of pulmonary PCM, and further studies combining the use of immunotherapy with antifungal drugs are encouraged.

Quantitative Peptidomics Using Reductive Methylation of Amines.

A number of different approaches have been used for quantitative peptidomics. In this protocol, we describe the method in which peptides are reacted with formaldehyde and sodium cyanoborohydride, which converts primary and secondary amines into tertiary amines. By using different combinations of regular reagents, deuterated reagents (2H), and reagents containing deuterium and 13C, it is possible to produce five isotopically distinct forms of the methylated peptides, which can be quantified by mass spectrometry. Peptides with free N-termini that are primary amines incorporate two methyl groups using this procedure, which differ by 2 Da for each of the five isotopic combinations. Peptides that contain unmodified lysine residues incorporate additional pairs of methyl groups, leading to larger mass differences between isotopic forms. The reagents are commercially available, relatively inexpensive, and chemically stable.

Methods for Intracellular Peptidomic Analysis.

Peptides have broad biological significance among different species. Intracellular peptides are considered a particular class of bioactive peptides, whose generation is initiated by proteasomal degradation of cytosolic, nuclear, or mitochondrial proteins. To extract and purify intracellular peptides, which may apply for biological peptides in general, it is important to consider the initial source: tissue, cell, or fluid. First, it is important to proceed fast with inactivation of proteases and/or peptidases commonly present in the biological source of peptides, which might rapidly degrade peptides during the initial process of extraction. The incubation of biological tissues, cells, and fluids at 80 °C for up to 20 min have been sufficient to fully inactivate proteases or peptidases activities. It is particularly important not to acidify the samples at high temperature, because it can lead to nonspecific hydrolysis reactions; particularly, the Asp-Pro peptide bond can be cleaved at acidic environments and elevated temperatures. Unfortunately, not every sample can have proteinases and peptidases denatured by heating the biological source of intracellular peptides. Plasma, for example, when heated at temperatures higher than 55 °C can clot and trap peptides within the fibrin net. Therefore, alternative conditions for inactivating proteinases and peptidases must apply for plasma samples. In this chapter, the most successful methods used in our laboratory to extract intracellular peptides are described.

Peptidomics of Zebrafish Brain in a 6-OHDA-Induced Neurodegeneration Model.

Bioactive peptides such as neuropeptides and peptide hormones are largely understood in their involvement in a variety of physiologic systems. In addition to the neuropeptides produced and processed by the classic secretory pathway, intracellular peptides (InPeps) have shown biological activity in studies involving different organisms. A model that has become attractive in many research fields is the zebrafish (Danio rerio), which has allowed correlating behavioral responses or physiological processes with underlying molecular pathways or signaling cascades, improving the understanding of homeostasis mechanisms of the central nervous system, as well as pathological processes such as neurodegenerative diseases. Here, we provide a detailed description of the protocol of treatment with 6-OHDA, which mimics some features of Parkinson's Disease, as well as the validation of the treatment by evaluation of the locomotor activity and the protocol of peptide extraction followed by isotopic labeling to peptide relative quantitation by mass spectrometry.

Complexed amino acid minerals vs. bis-glycinate chelated minerals: Impact on the performance of old laying hens.

The present study was to evaluate the effect of trace minerals (Zn, Mn, and Cu) from complexed amino acid minerals (ZMCAA) and bis-glycinate chelated minerals (ZMCGly) in laying hen diets on performance, internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. From 78 to 98 weeks of age, 400 White LSL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 × 2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low (20, 20, and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high (40, 40, and 7 mg/kg of Zn, Mn, and Cu, respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey's test (P < 0.05). The source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production (P = 0.01), egg weight (P = 0.02), egg mass (P = 0.01), and lower feed conversion ratio (P = 0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height (P = 0.01), albumen weight (P = 0.01), and eggshell thickness (P < 0.01). The deposition of Zn (P < 0.01), Mn (P < 0.01), and Cu (P < 0.01) in the egg yolk was greater for hens received ZMCAA. Tibia weight (P = 0.04) and bone densitometry (P < 0.01) in the tibia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi (P = 0.02) and shorter crypt depth (P = 0.01) in the duodenum. Jejunum and ileum measurements were influenced by the level and source of trace minerals (P < 0.05). Laying hens fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

Unusual Sesquiterpenes from Streptomyces olindensis DAUFPE 5622.

In nature, the vast majority of sesquiterpenes are produced by type I mechanisms, and glycosylated sesquiterpenes are rare in actinobacteria. Streptomyces olindensis DAUFPE 5622 produces the sesquiterpenes olindenones A-G, a new class of rearranged drimane sesquiterpenes. Olindenones B-D are oxygenated derivatives of olindenone A, while olindenones E-G are analogs glycosylated with dideoxysugars. 13C-isotope labeling studies demonstrated olindenone A biosynthesis occurs via the methylerythritol phosphate (MEP) pathway and suggested the rearrangement is only partially concerted. Based on the structures, one potential mechanism of olindenone A formation proceeds by cyclization of the linear terpenoid precursor, likely occurring via a terpene cyclase-mediated type II mechanism whereby the terminal alkene of the precursor is protonated, triggering carbocation-driven cyclization followed by rearrangement. Diphosphate hydrolysis may occur either before or after cyclization. Although a biosynthetic route is proposed, the terpene cyclase gene responsible for producing olindenones currently remains unidentified.

Breaking barriers in Candida spp. detection with Electronic Noses and artificial intelligence.

The timely and accurate diagnosis of candidemia, a severe bloodstream infection caused by Candida spp., remains challenging in clinical practice. Blood culture, the current gold standard technique, suffers from lengthy turnaround times and limited sensitivity. To address these limitations, we propose a novel approach utilizing an Electronic Nose (E-nose) combined with Time Series-based classification techniques to analyze and identify Candida spp. rapidly, using culture species of C. albicans, C.kodamaea ohmeri, C. glabrara, C. haemulonii, C. parapsilosis and C. krusei as control samples. This innovative method not only enhances diagnostic accuracy and reduces decision time for healthcare professionals in selecting appropriate treatments but also offers the potential for expanded usage and cost reduction due to the E-nose's low production costs. Our proof-of-concept experimental results, carried out with culture samples, demonstrate promising outcomes, with the Inception Time classifier achieving an impressive average accuracy of 97.46% during the test phase. This paper presents a groundbreaking advancement in the field, empowering medical practitioners with an efficient and reliable tool for early and precise identification of candidemia, ultimately leading to improved patient outcomes.

Diagnostic accuracy of ultrasonography in relation to salivary gland biopsy in Sjögren's syndrome: a systematic review with meta-analysis.

OBJECTIVES: To evaluate the accuracy of major salivary gland ultrasonography (SGUS) in relation to minor salivary gland biopsy (mSGB) in the diagnosis of Sjögren's syndrome (SS). METHODS: A systematic review and meta-analysis were performed. Ten databases were searched to identify studies that compared the accuracy of SGUS and mSGB. The risk of bias was assessed, data were extracted, and univariate and bivariate random-effects meta-analyses were done. RESULTS: A total of 5000 records were identified; 13 studies were included in the qualitative synthesis and 10 in the quantitative synthesis. The first meta-analysis found a sensitivity of 0.86 (95% CI: 0.74-0.92) and specificity of 0.87 (95% CI: 0.81-0.92) for the predictive value of SGUS scoring in relation to the result of mSGB. In the second meta-analysis, mSGB showed higher sensitivity and specificity than SGUS. Sensitivity was 0.80 (95% CI: 0.74-0.85) for mSGB and 0.71 (95% CI: 0.58-0.81) for SGUS, and specificity was 0.94 (95% CI: 0.87-0.97) for mSGB and 0.89 (95% CI: 0.82-0.94) for SGUS. CONCLUSIONS: The diagnostic accuracy of SGUS was similar to that of mSGB. SGUS is an effective diagnostic test that shows good sensitivity and high specificity, in addition to being a good tool for prognosis and for avoiding unnecessary biopsies. More studies using similar methodologies are needed to assess the accuracy of SGUS in predicting the result of mSGB. Our results will contribute to decision-making for the implementation of SGUS as a diagnostic tool for SS, considering the advantages of this method.

Potential of Ocotea indecora Essential Oil for Controlling Drosophila suzukii: Molecular Predictions for Toxicity and Selectivity to Beneficial Arthropods.

The protection of soft-skinned fruits against Drosophila suzukii has relied primarily on the efficacy of a few synthetic molecules. Despite their short-term efficacy, these molecules can cause environmental pollution, unintendedly affect non-target organisms, and fail to provide sustainable control. The shortfalls of using synthetic pesticides warrant the search for alternatives, such as essential oils extracted from plants, with greater eco-friendlier properties. Here, we chemically characterized and evaluated the toxicity of the essential oil extracted from leaves of Ocotea indecora (Schott) Mez (Lauraceae) against D. suzukii via two exposure pathways (ingestion and contact). We also assessed the selectivity of the essential oil to two predatory natural enemies, Eriopis connexa and Chrysoperla externa and two pollinator bees, Apis mellifera and Partamona helleri. In addition, we conducted in silico predictions to investigate potential interactions between the major compound of the essential oil and the insects' transient receptor potential (TRP) channels. Our chromatographic analysis revealed sesquirosefuran (87%) as the major compound. Higher toxicity to adults of D. suzukii was observed in contact exposure (LC50 = 0.43 µL mL-1) compared to ingestion (LC50 = 0.72 µL mL-1). However, the essential oil did not cause mortality to the non-target organisms tested here, even when applied at 2.20 µL mL-1. Molecular predictions demonstrated that sesquirosefuran binds more stably to the TRP channels of D. suzukii than to those expressed in beneficial arthropods. Collectively, our findings provide the initial framework for the potential use of O. indecora essential oil as a sustainable alternative for managing D. suzukii infestations.

Leveraging inter-individual transcriptional correlation structure to infer discrete signaling mechanisms across metabolic tissues.

Inter-organ communication is a vital process to maintain physiologic homeostasis, and its dysregulation contributes to many human diseases. Given that circulating bioactive factors are stable in serum, occur naturally, and are easily assayed from blood, they present obvious focal molecules for therapeutic intervention and biomarker development. Recently, studies have shown that secreted proteins mediating inter-tissue signaling could be identified by 'brute force' surveys of all genes within RNA-sequencing measures across tissues within a population. Expanding on this intuition, we reasoned that parallel strategies could be used to understand how individual genes mediate signaling across metabolic tissues through correlative analyses of gene variation between individuals. Thus, comparison of quantitative levels of gene expression relationships between organs in a population could aid in understanding cross-organ signaling. Here, we surveyed gene-gene correlation structure across 18 metabolic tissues in 310 human individuals and 7 tissues in 103 diverse strains of mice fed a normal chow or high-fat/high-sucrose (HFHS) diet. Variation of genes such as FGF21, ADIPOQ, GCG, and IL6 showed enrichments which recapitulate experimental observations. Further, similar analyses were applied to explore both within-tissue signaling mechanisms (liver PCSK9) and genes encoding enzymes producing metabolites (adipose PNPLA2), where inter-individual correlation structure aligned with known roles for these critical metabolic pathways. Examination of sex hormone receptor correlations in mice highlighted the difference of tissue-specific variation in relationships with metabolic traits. We refer to this resource as gene-derived correlations across tissues (GD-CAT) where all tools and data are built into a web portal enabling users to perform these analyses without a single line of code (gdcat.org). This resource enables querying of any gene in any tissue to find correlated patterns of genes, cell types, pathways, and network architectures across metabolic organs.

Adverse alcohol use and oral health.

OBJECTIVE: To determine whether different alcohol intake dimensions: average alcohol volume consumed (AVC), binge drinking (BD), and alcohol-related consequences (ARC) are associated with self-rated oral health (SROH). METHODS: Secondary cross-sectional analysis of The Brazilian National Health Survey of 2019 data. BD was considered when an individual reported a past-month heavy drinking episode. ARC referred to experiences such as past-year blackouts, concerns from others, or failure in routine activities. Adjusted multivariate Poisson regression models with robust variance were employed to calculate the prevalence ratios (PR) and 95% confidence intervals (CI) of SROH across the entire sample and stratified by sex and age. RESULTS: The sample comprised 88,531 participants aged 18 years or older. Individuals experiencing at least one past-year ARC had an 11% (95% CI: 1.07, 1.15) higher prevalence of poor SROH than their abstainers' counterparts. Associations were more pronounced among men aged less than 50 (PR = 1.09; 95% CI: 1.03, 1.15) and women aged 50 years or more (PR = 1.15; 95% CI: 1.01, 1.30). CONCLUSION: Alcohol-related consequences predicted poor SROH. Oral health inquiries should include the screening for ARC in addition to traditional measurements of AVC or BD, since such exposures may not fully capture the role of alcohol on oral health impairment.

Understanding the interaction between leukaemia stem cells and their microenvironment to improve therapeutic approaches.

Although chemotherapeutic regimens can eliminate blasts in leukaemia patients, such therapies are associated with toxicity and often fail to eliminate all malignant cells resulting in disease relapse. Disease relapse has been attributed to the persistence of leukaemia cells in the bone marrow (BM) with the capacity to recapitulate disease; these cells are often referred to as leukaemia stem cells (LSCs). Although LSCs have distinct characteristics in terms of pathobiology and immunophenotype, they are still regulated by their interactions with the surrounding microenvironment. Thus, understanding the interaction between LSCs and their microenvironment is critical to identify effective therapies. To this end, there are numerous efforts to develop models to study such interactions. In this review, we will focus on the reciprocal interactions between LSCs and their milieu in the BM. Furthermore, we will highlight relevant therapies targeting these interactions and discuss some of the promising in vitro models designed to mimic such relationship. LINKED ARTICLES: This article is part of a themed issue on Cancer Microenvironment and Pharmacological Interventions. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.2/issuetoc.

The high biodiversity of benthic organisms in a coastal ecosystem revealed by an integrative approach / A alta biodiversidade de organismos bentônicos em um ecossistema costeiro revelada por uma abordagem integrativa

Abstract Increasing habitat modification and species loss demand consistent efforts to describe and understand biodiversity patterns. The BIOTA/FAPESP Program was created in this context and it has been a successful initiative to promote studies on biodiversity and conservation in Brazil. The BIOTA/Araçá is an interdisciplinary project that provided a detailed evaluation of the biodiversity of Araçá Bay, a coastal seascape located on the North coast of the state of São Paulo, Southeast Brazil. The bay encompasses multiple habitats, such as beaches, mangroves, rocky shores, and a tidal flat, and provides important ecosystem services. Unfortunately, the bay is the subject of complex social-environmental conflicts that oppose economic, social, and environmental demands (i.e., the expansion of neighboring harbor activities vs. small-scale artisanal fisheries and protection of biodiversity). The present study presents a survey of the benthic species occurring in the different habitats of Araçá Bay, including data obtained during the BIOTA/Araçá project and previous assessments of the area. The benthic species play an important role in marine environments and studying the diversity of these organisms that live associated with the bottom is indispensable for comprehending the environment's functioning. The macrofauna, meiofauna, and microorganisms associated with soft and hard bottom were listed, and additional information, such as the habitat and geographical distribution, were provided for each species. The checklist includes 826 species, almost 70% recorded during the BIOTA/Araçá project. The most speciose taxa were the annelids (225 spp.), mollusks (194 spp.), and crustaceans (177 spp.). Seven benthic species are endemic to Araçá Bay, 14 are considered threatened, and seven are economically exploited. Furthermore, the bay is the type locality of many taxa, and 11 new benthic species were described based on specimens sampled during the project. This project shows the importance of Araçá Bay as a unique biologically rich environment and highlights the need for conservation efforts in light of the current threats.

Resumo O aumento da modificação dos habitats e da perda de espécies demanda esforços consistentes para descrever e compreender os padrões de biodiversidade. O programa BIOTA/FAPESP foi criado nesse contexto e é uma iniciativa de sucesso para promover estudos em biodiversidade e conservação no Brasil. O BIOTA/Araçá é um projeto interdisciplinar que promoveu uma avaliação detalhada da biodiversidade da Baía do Araçá, um ecossistema costeiro localizado ao Norte do estado de São Paulo, Sudeste do Brasil. A baía engloba múltiplos habitats, tais como praias, manguezais, costões rochosos, e uma planície de maré, e também fornece importantes serviços ecossistêmicos. Infelizmente, a baía está sujeita à conflitos sócio-ambientais complexos que contrastam demandas econômicas, sociais e ambientais (i.e. a expansão das atividades do porto vizinho vs. a pesca artesanal de pequena escala e a proteção da biodiversidade). O presente estudo apresenta um levantamento das espécies bentônicas que ocorrem nos diferentes habitats da Baía do Araçá, incluindo dados obtidos durante o projeto BIOTA/Araçá e de investigações realizadas anteriormente na área. As espécies bentônicas desempenham um papel importante no ambiente marinho, e estudar a diversidade desses organismos que vivem associados ao fundo é indispensável para compreender o funcionamento do meio ambiente. A macrofauna, meiofauna, e microorganismos associados aos fundos consolidado e inconsolidado foram listados, e informações adicionais foram fornecidas para cada espécie, tais como a distribuição geográfica e nos habitats. O checklist inclui 826 espécies, quase 70% registradas durante o projeto BIOTA/Araçá. Os taxa mais especiosos foram os anelídeos (225 spp.), moluscos (194 spp.), e crustáceos (177 spp.). Entre as espécies bentônicas listadas, sete são endêmicas da Baía do Araçá, 14 são consideradas ameaçadas de extinção, e sete são exploradas economicamente. A baía é a localidade tipo de vários taxa, e 11 novas espécies bentônicas foram descritas com base em espécimes amostrados durante o projeto. Este projeto mostra a importância da Baía do Araçá como um ambiente de riqueza biológica única e demonstra a necessidade de esforços para a sua conservação considerando as atuais ameaças.

Temporal trends of blood eosinophilia in severe uncontrolled CRSwNP treated with dupilumab: a real-life study.

PURPOSE: Induced eosinophilia is commonly related to dupilumab treatment. We analysed the temporal trends of blood eosinophilia in patients with severe uncontrolled CRSwNP during the first year of treatment with dupilumab in real-life setting to evaluate its correlation with outcomes of response and adverse events (AEs). METHODS: Seventy-four patients with severe uncontrolled CRSwNP treated with dupilumab at our institution were enrolled. At each visit, we evaluated AEC, outcomes of response to treatment and AEs. RESULTS: A significant increase in AEC was observed since the first month with a peak at 3 months; at 12 months, the values returned comparable to those at baseline. A ≥ 50% increase of the baseline AEC with a value greater than 500 cells/mm3 was documented in 38/74 patients (Group A) regardless of the time of observation, whereas in 36/74 patients (Group B), no changes were observed. Analysing the blood eosinophilia trend over time in group A, we observed a temporary eosinophilia with early onset (within 6 months), persistent eosinophilia with early onset, and eosinophilia with late onset. No differences in terms of outcomes of response to treatment or AEs were found between Group A and Group B, or between patients who developed an AEC ≥ 1500 cells/mm3 or not. CONCLUSION: In our series, we observed that an increase in AEC with different temporal trends may be observed in CRSwNP patients during the first year of treatment with dupilumab. In our series, eosinophilia is not correlated with a negative outcome of response to treatment or a risk of AEs.

Light-Driven Tetra- and Octa-ß-substituted Cationic Zinc(II) Phthalocyanines for Eradicating Fusarium oxysporum Conidia.

Photodynamic inactivation (PDI) is an emerging therapeutic approach that can effectively inactivate diverse microbial forms, including vegetative forms and spores, while preserving host tissues and avoiding the development of resistance to the photosensitization procedure. This study evaluates the antifungal and sporicidal photodynamic activity of two water-soluble amphiphilic tetra- and octa-ß-substituted zinc(II) phthalocyanine (ZnPc) dyes with dimethylaminopyridinium groups at the periphery (ZnPcs 1, 2) and their quaternized derivatives (ZnPcs 1a, 2a). Tetra(1, 1a)- and octa(2, 2a)-ß-substituted zinc(II) phthalocyanines were prepared and assessed as photosensitizers (PSs) for their effects on Fusarium oxysporum conidia. Antimicrobial photoinactivation experiments were performed with each PS at 0.1, 1, 10, and 20 µM under white light irradiation at an irradiance of 135 mW·cm-2, for 60 min (light dose of 486 J·cm-2). High PDI efficiency was observed for PSs 1a, 2, and 2a (10 µM), corresponding to inactivation until the method's detection limit. PS 1 (20 µM) also achieved a considerable reduction of >5 log10 in the concentration of viable conidia. The quaternized PSs (1a, 2a) showed better PDI performance than the non-quaternized ones (1, 2), even at the low concentration of 1 µM, and a light dose of 486 J·cm-2. These cationic phthalocyanines are potent photodynamic drugs for antifungal applications due to their ability to effectively inactivate resistant forms, like conidia, with low concentrations and reasonable energy doses.