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.

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.

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.

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.

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.

Enzymatic Modulators from Induratia spp.

In the present work, ethyl acetate extracts, consisting of non-volatile compounds, from the culture of endophytic fungi isolated from coffee plants, Induratia coffeana and Induratia yucatanensis, were prospected in enzyme modulation tests that act in human hemostasis. Dry extracts of the fungi were diluted in dimethyl sulfoxide p.a. 99.9% (DMSO), and then tested. Bothrops atrox venom was used as an enzyme source and tool to induce the activities. Prior to the evaluation of the activities, incubations of the extracts with the venom were performed in the proportions 1: 0.01, 1: 0.25, 1: 0.5, and 1: 1 (venom: extract; mass: mass). The extracts of all fungi promoted a significant increase in the clotting time induced by the venom, which was even longer when the extracts were previously incubated with the citrated plasma. The activity of phospholipases A2 did not significantly change when evaluated in the presence of fungal extracts. However, the evaluated extracts inhibited proteases by 73% and 30% in the thrombolytic and caseinolytic tests, respectively. In addition, the extracts did not induce cytotoxicity on human erythrocytes when evaluated in the absence of the venom. Thus, it is possible to suggest the presence of specific interactions between molecules present in extracts of Induratia spp. and venom proteases, highlighting non-volatile metabolites as promising sources of compounds of medical and scientific interest.

Environmental characterization of 4,4'-dichlorobenzophenone in surface waters from Macao and Hong Kong coastal areas (Pearl River Delta) and its toxicity on two biological models: Artemia salina and Daphnia magna.

The Pearl River Delta (PRD) is one of the areas with higher environmental concentration of organochlorine pesticides (OCPs), being DDT one of the most abundant. In this work, 4,4'-dichlorobenzophenone (4,4'-DCBP), a common metabolite of dicofol (DDT related) and DDT, was quantified in surface waters of Hong Kong and Macao, together with the analysis of physicochemical and nutrients parameters. Hong Kong presented higher 4,4'-DCBP mean levels (12.50 ng/L) than Macao (4.05 ng/L), which may be due to the use of dicofol as a pesticide and DDT as antifouling-paint for ships. The region presented a possible eutrophication state due to the high nutrients' concentration. For the first time, toxicity evaluation of this metabolite in Artemia salina and Daphnia magna was done, in order to compute valid EC50s and theoretically evaluate the risk in the PRD. The toxicity results (EC50 = 0.27 mg/L for A. salina; and EC50 = 0.17 mg/L and LC50 = 0.26 mg/L for D. magna), together with the 4,4'-DCBP levels quantified, indicated a low environmental risk.

Production and chemical characterization of pigments in filamentous fungi.

Production of pigments by filamentous fungi is gaining interest owing to their use as food colourants, in cosmetics and textiles, and because of the important biological activities of these compounds. In this context, the objectives of this study were to select pigment-producing fungi, identify these fungi based on internal transcribed spacer sequences, evaluate the growth and pigment production of the selected strains on four different media, and characterize the major coloured metabolites in their extracts. Of the selected fungal strains, eight were identified as Aspergillus sydowii (CML2967), Aspergillus aureolatus (CML2964), Aspergillus keveii (CML2968), Penicillium flavigenum (CML2965), Penicillium chermesinum (CML2966), Epicoccum nigrum (CML2971), Lecanicillium aphanocladii (CML2970) and Fusarium sp. (CML2969). Fungal pigment production was influenced by medium composition. Complex media, such as potato dextrose and malt extract, favoured increased pigment production. The coloured compounds oosporein, orevactaene and dihydrotrichodimerol were identified in extracts of L. aphanocladii (CML2970), E. nigrum (CML2971), and P. flavigenum (CML2965), respectively. These results indicate that the selected fungal strains can serve as novel sources of pigments that have important industrial applications.

Partial least squares model and design of experiments toward the analysis of the metabolome of Jatropha gossypifolia leaves: Extraction and chromatographic fingerprint optimization.

A major challenge in metabolomic studies is how to extract and analyze an entire metabolome. So far, no single method was able to clearly complete this task in an efficient and reproducible way. In this work we proposed a sequential strategy for the extraction and chromatographic separation of metabolites from leaves Jatropha gossypifolia using a design of experiments and partial least square model. The effect of 14 different solvents on extraction process was evaluated and an optimized separation condition on liquid chromatography was estimated considering mobile phase composition and analysis time. The initial conditions of extraction using methanol and separation in 30 min between 5 and 100% water/methanol (1:1 v/v) with 0.1% of acetic acid, 20 µL sample volume, 3.0 mL min(-1) flow rate and 25°C column temperature led to 107 chromatographic peaks. After the optimization strategy using i-propanol/chloroform (1:1 v/v) for extraction, linear gradient elution of 60 min between 5 and 100% water/(acetonitrile/methanol 68:32 v/v with 0.1% of acetic acid), 30 µL sample volume, 2.0 mL min(-1) flow rate, and 30°C column temperature, we detected 140 chromatographic peaks, 30.84% more peaks compared to initial method. This is a reliable strategy using a limited number of experiments for metabolomics protocols.

Longitudinal impact of the Cyber Friendly Schools program on adolescents' cyberbullying behavior.

Cyberbullying is a major public health problem associated with serious mental, social, and academic consequences for young people. To date, few programs addressing cyberbullying have been developed and empirically tested. The Cyber Friendly Schools (CFS) group-randomized controlled trial measured the longitudinal impact of a whole-school online cyberbullying prevention and intervention program, developed in partnership with young people. Non-government secondary schools in Perth, Western Australia, (N = 35; 3,000+ students) were randomized to an intervention (n = 19) or usual practice control group (n = 16 schools). Students completed online questionnaires in 2010, 2011, and at 1-year follow-up in 2012, measuring their cyberbullying experiences during the previous school term. The intervention group received the program in Grades 8 and 9 (aged 13-14 years). Program effects were tested using two-part growth models. The program was associated with significantly greater declines in the odds of involvement in cyber-victimization and perpetration from pre- to the first post-test, but no other differences were evident between the study conditions. However, teachers implemented only one third of the program content. More work is needed to build teacher capacity and self-efficacy to effectively implement cyberbullying programs. Whole-school cyberbullying interventions implemented in conjunction with other bullying prevention programs may reduce cyber-victimization more than traditional school-based bullying prevention programs alone. Aggr. Behav. 42:166-180, 2016. © 2015 Wiley Periodicals, Inc.

Aqueous self-assembly and cation selectivity of cobaltabisdicarbollide dianionic dumbbells.

The anion [3,3'-Co(C2B9H11)2](-) ([COSAN](-)) produces aggregates in water. These aggregates are interpreted to be the result of C-H⋅⋅⋅H-B interactions. It is possible to generate aggregates even after the incorporation of additional functional groups into the [COSAN](-) units. The approach is to join two [COSAN](-) anions by a linker that can adapt itself to act as a crown ether. The linker has been chosen to have six oxygen atoms, which is the ideal number for K(+) selectivity in crown ethers. The linker binds the alkaline metal ions with different affinities; thus showing a distinct degree of selectivity. The highest affinity is shown towards K(+) from a mixture containing Li(+), Na(+), K(+), Rb(+) and Cs(+); this can be indicative of pseudo-crown ether performance of the dumbbell. One interesting possibility is that the [COSAN](-) anions at the two ends of the linker can act as a hook-and-loop fastener to close the ring. This facet is intriguing and deserves further consideration for possible applications. The distinct affinity towards alkaline metal ions is corroborated by solubility studies and isothermal calorimetry thermograms. Furthermore, cryoTEM micrographs, along with light scattering results, reveal the existence of small self-assemblies and compact nanostructures ranging from spheres to single-/multi-layer vesicles in aqueous solutions. The studies reported herein show that these dumbbells can have different appearances, either as molecules or aggregates, in water or lipophilic phases; this offers a distinct model as drug carriers.

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.

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.

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.