Nonfebrile Seizures in Pediatrics: Key Points to Remember.

Seizures are the most common neurological disorder in pediatrics, and their initial approach aims at clinical stabilization. A thorough patient evaluation may provide important clues for the etiological diagnosis. A 12-month-old female child was observed in the emergency department after experiencing her first apyretic seizure. She had a history of congenital alopecia and, on physical examination, presented subtotal alopecia and milia. Initial investigation revealed hypocalcemia; therefore, intravenous calcium correction was started with a partial response. The analytical study was extended, revealing hypophosphatemia, elevated parathormone, and 1,25(OH)2 vitamin D with normal 25(OH) vitamin D. The genetic analysis confirmed hereditary vitamin D-resistant rickets (HVDRR). The integration of the findings was crucial to diagnostic reasoning and to guide further investigation. HVDRR is a rare disorder, with more severe clinical presentations associated with alopecia. Early diagnosis and treatment are fundamental to minimize the impact on growth and the development of other comorbidities.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Seasonal characterization of mercury contamination along the Portuguese coast: human health and environmental risk assessment.

A seasonal characterization of mercury (Hg) accumulation in three different estuaries along the Portuguese coast (i.e. Ria de Aveiro, Tagus estuary and Ria Formosa) was done. For that, it was evaluated: (1) Hg concentrations in abiotic (water) and biotic matrices (flora and fauna); (2) the risk of consumption of local seafood species (e.g. bivalves) to human health; and (3) the environmental risk to Hg exposure. During 1 year, water and biological samples were collected during low tide, in each system for Hg quantification. Our findings revealed that total Hg concentrations in surface waters were higher in Ria de Aveiro and Tagus estuary than in Ria Formosa. In Ria de Aveiro, a particular attention should be given in autumn periods, where Hg levels (≈ 100 µg L-1) were considered quite high according to European quality parameters. The same was observed for the Tagus estuary during spring time. Regarding macrofauna Hg levels, no clear seasonal trend was observed. Also, total Hg concentrations in edible species (< 0.5 µg. g-1 ww) represent no risk for consumption. However, considering the environmental risk, in Ria de Aveiro, there is a moderate risk (RQ > 0.1) in autumn periods, which can be a matter of concern.

Biomarkers Associated with Thrombosis in Patients with Peripherally Inserted Central Catheter: A Systematic Review and Meta-Analysis.

BACKGROUND: The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC). OBJECTIVES: This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT. METHODS: Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871). RESULTS: Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 µg/mL, 95% CI 0.02, 0.72; p = 0.04, I2 = 92%; p for heterogeneity < 0.00001) and with higher platelets (8.76 × 109/L, 95% CI 1.62, 15.91; p = 0.02, I2 = 41%; p for heterogeneity = 0.06). CONCLUSIONS: High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.

Different concentrations of fetal bovine serum affect cytokine modulation in Lipopolysaccharide-activated apical papilla cells in vitro.

BACKGROUND: Fetal bovine serum (FBS) is the most used supplement in culture media; however, it may interfere with in vitro assays via effects on cell proliferation and cytokine production. The ideal FBS concentration for assays using apical papilla cells (APCs) remains unknown. Therefore, this study aimed to evaluate the effects of FBS on APC activation, cell viability/proliferation, and cytokine production. METHODOLOGY: Human APCs were cultured, plated, and maintained in media containing increasing concentrations of FBS for 24 h, 48 h, 72 h, 7 days, and 14 days in the presence of Lipopolysaccharide (LPS - 1 µg/mL). At each time point, the cells were subjected to the MTT assay. The cytokines transforming growth factor (TGF)-ß1, osteoprotegerin (OPG), and interleukin (IL)-6, along with the chemokine CCL2, were quantified using the enzyme-linked immunosorbent assay at the 24-h time-point. Statistical analysis was performed using two-way analysis of variance (ANOVA) followed by Tukey's post-hoc test (p<0.05). RESULTS: In general, APCs exhibited increasing metabolic activity in an FBS concentration-dependent fashion, regardless of the presence of LPS. In contrast, FBS interfered with the production of all the cytokines evaluated in this study, affecting the response induced by the presence of LPS. CONCLUSION: FBS increased APC metabolism in a concentration-dependent manner and differentially affected the production of TGF-ß1, OPG, IL-6, and CCL2 by APCs in vitro.

Elastic Provisioning of Network and Computing Resources at the Edge for IoT Services.

The fast growth of Internet-connected embedded devices demands new system capabilities at the network edge, such as provisioning local data services on both limited network and computational resources. The current contribution addresses the previous problem by enhancing the usage of scarce edge resources. It designs, deploys, and tests a new solution that incorporates the positive functional advantages offered by software-defined networking (SDN), network function virtualization (NFV), and fog computing (FC). Our proposal autonomously activates or deactivates embedded virtualized resources, in response to clients' requests for edge services. Complementing existing literature, the obtained results from extensive tests on our programmable proposal show the superior performance of the proposed elastic edge resource provisioning algorithm, which also assumes an SDN controller with proactive OpenFlow behavior. According to our results, the maximum flow rate for the proactive controller is 15% higher; the maximum delay is 83% smaller; and the loss is 20% smaller compared to when the non-proactive controller is in operation. This improvement in flow quality is complemented by a reduction in control channel workload. The controller also records the time duration of each edge service session, which can enable the accounting of used resources per session.

Combined Effects of Temperature and Dietary Lipid Level on Body Composition, Growth, and Freshness Profile in European Seabass, Dicentrarchus labrax.

A fish trial was carried out to evaluate the combined effects of temperature and dietary lipid level on the body composition, growth performance, and freshness profile of the European seabass (Dicentrarchus labrax). Fish were kept for 56 days at 20 °C and 24 °C and fed on two diets, with 16% and 20% lipid. At the end of the trial, fish were euthanized at two temperature conditions (0.6 °C or -0.6 °C) and kept on ice for 10 days at 4 °C to evaluate their freshness condition. Findings demonstrated that fish reared at 24 °C presented a lower lipid level and a higher daily growth index than those at 20 °C. Additionally, sensory analysis (Quality Index Method-QIM) and microbiological analysis revealed that fish reared at 24 °C showed better freshness conditions than those at 20 °C. However, the 16S rRNA metabarcoding analyses revealed a higher proliferation of genera associated with fish-spoiling bacteria in the skin microbiome of fish reared at 24 °C, i.e., Vibrio and Acinetobacter, which was not observed in the skin microbiome of fish reared at 20 °C. Nevertheless, the dietary lipid level did not have any influence on fish freshness. Therefore, our data suggest that the increase in temperature to 24 °C is beneficial for the growth and freshness profile (lower QIM and lower CFUs/cm2) of this particular species. Additionally, the lower euthanasia temperature (-0.6 °C) seems to lead to higher fish freshness than the normal temperature (0.6 °C).

Endophytic species of Induratia from coffee and carqueja plants from Brazil and its potential for the biological control of toxicogenic fungi on coffee beans by means of antimicrobial volatiles.

Several endophytic fungi have been reported to have produced bioactive metabolites. Some of them, including the Induratia species, have the capacity to emit volatile compounds with antimicrobial properties with broad spectrum against human and plant pathogens. The present study aimed to prospect the Induratia species producing volatile organic compounds (VOCs), in carqueja plants used in alternative medicine and coffee plants in Brazil. A total of 11 fungal isolates producing volatile metabolites were obtained by a parallel growth technique, using I. alba 620 as a reference strain. Phylogenetic relationships revealed the presence of at least three distinct species, I. coffeana, I. yucatanensis, and Induratia sp. SPME/GC/MS analyses of the VOCs in the headspace above the mycelium from Induratia species cultured for 10 days on PDA revealed the volatile profile emitted by I. coffeana CCF 572, I. coffeana COAD 2055, I. yucatanensis COAD 2062, and Induratia sp. COAD 2059. Volatile organic compounds produced by I. coffeana isolates presented antimicrobial activity against Aspergillus ochraceus, A. sclerotiorum, A. elegans, A. foetidus, A. flavus, A. tamari, A. tubingensis, A. sydowii, A. niger, A. caespitosus, A. versicolor, and A. expansum, sometimes by decreasing the growth rate or, mainly, by fully inhibiting colony growth. Fifty-eight percent of the target species died after 6 days of exposure to VOCs emitted by I. coffeana CCF 572. In addition, VOCs emitted by the same fungus inhibited the growth in A. ochraceus inoculated into coffee beans, which indicates that plants which have I. coffeana as an endophyte may be protected from attacks by this plant pathogen.

Quantification of insecticides in commercial seafood sold in East Asian markets: risk assessment for consumers.

The extraction of 21 insecticides and 5 metabolites was performed using an optimized and validated QuEChERS protocol that was further used for the quantification (GC-MS/MS) in several seafood matrices (crustaceans, bivalves, and fish-mudskippers). Seven species, acquired from Hong Kong and Macao wet markets (a region so far poorly monitored), were selected based on their commercial importance in the Indo-Pacific region, market abundance, and affordable price. Among them, mussels from Hong Kong, together with mudskippers from Macao, presented the highest insecticide concentrations (median values of 30.33 and 23.90 ng/g WW, respectively). Residual levels of fenobucarb, DDTs, HCHs, and heptachlors were above the established threshold (10 ng/g WW) for human consumption according to the European and Chinese legislations: for example, in fish-mudskippers, DDTs, fenobucarb, and heptachlors (5-, 20- and tenfold, respectively), and in bivalves, HCHs (fourfold) had higher levels than the threshold. Risk assessment revealed potential human health effects (e.g., neurotoxicity), especially through fish and bivalve consumption (non-carcinogenic risk; ΣHQLT > 1), and a potential concern of lifetime cancer risk development through the consumption of fish, bivalves, and crustaceans collected from these markets (carcinogenic risk; ΣTCR > 10-4). Since these results indicate polluted regions, where the seafood is collected/produced, a strict monitoring framework should be implemented in those areas to improve food quality and safety of seafood products.

Different concentrations of fetal bovine serum affect cytokine modulation in Lipopolysaccharide-activated apical papilla cells in vitro

Abstract Fetal bovine serum (FBS) is the most used supplement in culture media; however, it may interfere with in vitro assays via effects on cell proliferation and cytokine production. The ideal FBS concentration for assays using apical papilla cells (APCs) remains unknown. Therefore, this study aimed to evaluate the effects of FBS on APC activation, cell viability/proliferation, and cytokine production. Methodology Human APCs were cultured, plated, and maintained in media containing increasing concentrations of FBS for 24 h, 48 h, 72 h, 7 days, and 14 days in the presence of Lipopolysaccharide (LPS - 1 µg/mL). At each time point, the cells were subjected to the MTT assay. The cytokines transforming growth factor (TGF)-β1, osteoprotegerin (OPG), and interleukin (IL)-6, along with the chemokine CCL2, were quantified using the enzyme-linked immunosorbent assay at the 24-h time-point. Statistical analysis was performed using two-way analysis of variance (ANOVA) followed by Tukey's post-hoc test (p<0.05). Results In general, APCs exhibited increasing metabolic activity in an FBS concentration-dependent fashion, regardless of the presence of LPS. In contrast, FBS interfered with the production of all the cytokines evaluated in this study, affecting the response induced by the presence of LPS. Conclusion FBS increased APC metabolism in a concentration-dependent manner and differentially affected the production of TGF-β1, OPG, IL-6, and CCL2 by APCs in vitro.

Viabilidade de fibroblastos do ligamento periodontal estimulados com sobrenadante necrótico de células de polpa dental in vitro / Viability of periodontal ligament fibroblasts stimulated with necrotic supernatant from dental pulp cells in vitro

As células necróticas são capazes de induzir a instalação de processos inflamatórios importantes, mesmo em ambientes estéreis, e o papel de remanescentes necróticos pulpares ainda não é conhecido na periodontite apical. O objetivo deste estudo foi investigar a capacidade de modulação in vitro de fibroblastos do ligamento periodontal (FLP) pelo sobrenadante necrótico (SN) de polpa dental. Cultura de fibroblastos de polpa dental (FPD) (n=1) e de ligamento periodontal (n=1) foram obtidas a partir do biobanco. Os FPDs passaram por ciclos de congelamento/descongelamento e o SN submetido a diluições 1/2, 1/10 e 1/20. Os FLPs foram estimulados com o SN de FPD. Para avaliar se o SN interfere na viabilidade celular do FLP foi realizado o ensaio de alamarBlue nos períodos de 24h, 48h e 72h. Nos grupos 24h, 48h e 72h não se observou diferença estatisticamente significativa. Porém, foi notado que no grupo de 72h o tratamento com SN resultou em uma maior ativação celular nas concentrações 1/10 e 1/20 em relação ao controle (p<00,5). O ensaio de MTT avaliou o efeito do SN na viabilidade celular do FLP. No grupo de 24h o SN resultou em uma ativação celular expressiva nas concentrações 1/2, 1/10 e 1/20 em relação ao controle. Nos grupos 48h e 72h não houve diferença estatisticamente significativa (p< 0,05). Os FLPs foram tratados com SN de FPD para avaliar os efeitos da produção de citocinas. A produção de OPG se apresentou maior no grupo com diluição 1/2 em comparação com as demais (p<0,05). A IL-6 apresentou-se aumentada no grupo com menor diluição e reduzida nos grupos com SN mais diluído (p<0,05). A expressão de CCL2 demonstrou-se menor nos grupos com diluição 1/10 e 1/20 (p<0,05). Diante desses resultados, observou-se que o sobrenadante de fibroblastos de polpa dental foi capaz de ativar células de ligamento periodontal in vitro modulando a produção de OPG, IL-6 e CCL2 de forma diluição-dependente.

Arcopilus eremanthusum sp. nov. as sources of antibacterial and antioxidant metabolites.

In this study, we evaluated the antibacterial and antioxidant activities of ethyl acetate (EtOAc) extracts of Arcopilus eremanthusum sp. nov. (CML3766) isolated from E. erythopappus. The fungi were identified using the sequences of the internal transcribed spacer (ITS), large subunit (LSU), and RNA polymerase II second largest subunit (RPB2). Antibacterial activity was determined using the minimum bactericidal concentration (MBC) method. Antioxidant activity was evaluated using free radical scavenging methods with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+) assays and the ß-carotene-linoleic acid system. The total phenolic compound content was measured using the Folin-Ciocalteu method. The endophytic fungal extract presented bactericidal activity, with an MBC of 2.44 and 19.5 µg/mL against Staphylococcus aureus GL 8702 and GL 5674, respectively, and 625 µg/mL for Salmonella enterica serovar Enteritidis. In addition, this fungus demonstrated an antioxidant activity of 52.30% protection in the ß-carotene method. The total concentration of phenolic compounds was 23.73 mg gallic acid equivalent (GAE)/g. Ferulic acid, trans-cinnamic acid, chlorogenic acid, catechin, vanillin, p-coumaric acid, and caffeic acid were quantified using high-performance liquid chromatography with diode array detection. The results demonstrate the potential of A. eremanthusum sp. nov. to serve as a source of antibacterial and antioxidant metabolites with possible future biotechnological applications.

How can environmental conditions influence dicofol genotoxicity on the edible Asiatic clam, Meretrix meretrix?

Genotoxic effects of dicofol on the edible clam Meretrix meretrix were investigated through a mesocosm experiment. Individuals of M. meretrix, were exposed to environmental concentration (D1 = 50 ng/L) and supra-environmental concentration (D2 = 500 ng/L) of dicofol for 15 days, followed by the same depuration period. DNA damage (i.e., strand breaks and alkali-labile sites) was evaluated at day 1, 7 and 15, during uptake and depuration, using Comet assay (alkaline version) and nuclear abnormalities (NAs) as genotoxicity biomarkers. The protective effects of dicofol against DNA damage induced by ex vivo hydrogen peroxide (H2O2) exposure were also assessed. Comet assay results revealed no significant DNA damages under dicofol exposure, indicating 1) apparent lack of genotoxicity of dicofol to the tested conditions and/or 2) resistance of the animals due to optimal adaptation to stress conditions. Moreover, ex vivo H2O2 exposure showed an increase in the DNA damage in all the treatments without significant differences between them. However, considering only the DNA damage induced by H2O2 during uptake phase, D1 animals had significantly lower DNA damage than those from other treatments, revealing higher protection against a second stressor. NAs data showed a decrease in the % of cells with polymorphic, kidney shape, notched or lobbed nucleus, along the experiment. The combination of these results supports the idea that the clams used in the experiment were probably collected from a stressful environment (in this case Pearl River Delta region) which could have triggered some degree of adaptation to those environmental conditions, explaining the lack of DNA damages and highlighting the importance of organisms' origin and the conditions that they were exposed during their lives.

Metabolites from Induratia spp. modulating key enzymes in human hemostasis.

Induratia spp. fungi have been poorly evaluated for their non-volatile secondary metabolites. In the present work, we evaluated the effects of non-volatile secondary metabolites released into the culture medium by Induratia spp. upon toxic alterations induced by Bothrops spp. venoms. B. atrox venom phospholipase was inhibited by Induratia spp. around 12 and 16%. The extracts of the two strains inhibited 12-25% of the hemolysis induced by B.moojeni venom. Thrombolysis was inhibited by 30-60% by the compounds present in both extracts. The coagulation induced by B. moojeni venom was prolonged by 26-41 s by the action of the extracts of I. coffeana. The fungal extracts did not exert any cytotoxic effect, nor did they induce any alteration in the other evaluated substrates show the potential use of non-volatile metabolites produced by the fungi evaluated as enzyme modulators, especially for proteases with a fundamental role in human hemostasis.

Endophytic Fungi Assures Tropical Forage Grass Growth by Water Stress Tolerances.

Forage plants is the base of beef and dairy cattle production. While water stress limits agricultural production worldwide, endophytic fungi can play a beneficial role for plants, such as tolerance to biotic and abiotic stresses. The objective of this work was to evaluate the effect of inoculation of the endophytic fungi Paraconiothyrium estuarinum (CML 3695, CML 3696, CML 3699) and Paraconiothyrium cyclothyrioides (CML 3697, CML 3698) on agronomic characteristics of two forage species, Brachiaria brizantha (A. Rich) Stapf. cv. Marandu and Megathyrsus maximus Jacq. cv. BRS Mombaça, under different available water capacities. The treatments simulated a long drought period (LDH) equivalent to 10% of the available water capacity (AWC) and simulated 7 (7 DH) and 14 days of drought (14 DH) without water supply. The grasses were evaluated for length and dry weight of shoots and roots. All treatments reached humidity below the permanent wilting point (PWP) and the highest variation in soil moisture was observed at 14 DH, for both grass species. The endophytic fungi promoted an average 15% increase in shoot length (SL) for B. brizantha and an increase of 34% for SL, 266% for Dry Shoot Mass (SDM), and 340% for Dry Root Mass (RDM) for M. maximus treated with P. estuarinum (CML 3699) at 7 DH. Paraconiothyrium estuarinum (CML 3699) guaranteed the highest tolerance to water deficit and sustainable growth performance to both tested grasses.

Antiviral fungal metabolites and some insights into their contribution to the current COVID-19 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, which started in late 2019, drove the scientific community to conduct innovative research to contain the spread of the pandemic and to care for those already affected. Since then, the search for new drugs that are effective against the virus has been strengthened. Featuring a relatively low cost of production under well-defined methods of cultivation, fungi have been providing a diversity of antiviral metabolites with unprecedented chemical structures. In this review, we present viral RNA infections highlighting SARS-CoV-2 morphogenesis and the infectious cycle, the targets of known antiviral drugs, and current developments in this area such as drug repurposing. We also explored the metabolic adaptability of fungi during fermentation to produce metabolites active against RNA viruses, along with their chemical structures, and mechanisms of action. Finally, the state of the art of research on SARS-CoV-2 inhibitors of fungal origin is reported, highlighting the metabolites selected by docking studies.

Recent Findings in Azaphilone Pigments.

Filamentous fungi are known to biosynthesize an extraordinary range of azaphilones pigments with structural diversity and advantages over vegetal-derived colored natural products such agile and simple cultivation in the lab, acceptance of low-cost substrates, speed yield improvement, and ease of downstream processing. Modern genetic engineering allows industrial production, providing pigments with higher thermostability, water-solubility, and promising bioactivities combined with ecological functions. This review, covering the literature from 2020 onwards, focuses on the state-of-the-art of azaphilone dyes, the global market scenario, new compounds isolated in the period with respective biological activities, and biosynthetic pathways. Furthermore, we discussed the innovations of azaphilone cultivation and extraction techniques, as well as in yield improvement and scale-up. Potential applications in the food, cosmetic, pharmaceutical, and textile industries were also explored.