Bilastine 0.6% preservative-free eye drops, an effective once-daily treatment to reduce signs and symptoms of allergic conjunctivitis: A pooled analysis of two randomized clinical trials.

BACKGROUND AND OBJECTIVE: Allergic conjunctivitis is the most common type of ocular allergy. The objective of this study was to evaluate the efficacy of a new once-daily, preservative-free, bilastine 0.6% eye drop formulation for the treatment of allergic conjunctivitis. METHODS: Two double-masked, vehicle controlled, clinical studies (a Phase 2 Dose Ranging Study and a Phase 3 Efficacy Study) were conducted to assess the efficacy of bilastine ophthalmic solution for the treatment of signs and symptoms of allergic conjunctivitis. Both studies used the Ora-CAC® Conjunctival Allergen Challenge (CAC) Model to allow observations of allergic responses under controlled conditions. Each study was analyzed separately and then combined to create an integrated dataset. RESULTS: Efficacy was achieved for the primary efficacy endpoint of ocular itching for three bilastine concentrations (0.2%, 0.4%, and 0.6%) at 15 minutes and 8 hours post-instillation and bilastine 0.6% ophthalmic solution was also efficacious at 16 hours post-instillation. Bilastine 0.6% ophthalmic solution demonstrated non-inferiority to ketotifen 0.025% at the onset of action. From the integrated data set, differences between vehicle and bilastine 0.6% were significant at all time points both at onset (15 minutes) and at a prolonged duration (16 hours) after instillation. CONCLUSION: This multi-trial assessment suggests that bilastine 0.6% ophthalmic solution is efficacious for the treatment of the signs and symptoms of allergic conjunctivitis, with a rapid and prolonged duration of action, and has a favorable safety profile. The added convenience of a once-a-day dosing regimen may contribute to patient adherence and improve their quality of life.

Salivary biomarkers present in patients with periodontitis without clinical distinction: findings from a meta-analysis.

BACKGROUND: A new classification for periodontitis has been adopted in clinical practice. However, there are still discussions regarding this new classification and difficulties in its adoption, both by professionals and researchers. Thus, this study aimed to evaluate which salivary biomarkers are present in periodontitis, following the new classification of periodontal diseases through meta-analysis. MATERIAL AND METHODS: A literature search was carried out in the scientific databases: PubMed, Scielo and Google scholar to select studies. The selection of studies was followed by two authors upon reading of the title, abstract and full text. The necessary data were collected and statistical analyses were performed using the Review Manager statistical software version 5.4, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05. RESULTS: After following the selection criteria, 9 articles were selected for comparison. The studies address the presence of biomarkers in the saliva of patients with periodontitis and their possible use in the monitoring and diagnosis of the disease. For the meta-analytic comparison, a sample size of 1,983 individuals was used. Statistical analyses showed that nitric oxide, IL-6, IL-1B and osteoprotegerin are substances that are significantly present in patients with periodontitis (P < 0.05). CONCLUSIONS: IL-6, nitric oxide, IL-1B, TNF-α and osteoprotegerin are among the most present biomarkers in patients with periodontitis, and may be used in the future as a monitoring of periodontal disease. The present study also revealed that there was no statistically significant difference in the concentration of these biomarkers for clinical distinction from periodontitis.

Bilastine 0.6% preservative-free eye drops, a once-daily treatment for allergic conjunctivitis.

BACKGROUND: Bilastine is a second-generation antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. This trial evaluated the efficacy and safety of a new bilastine 0.6% preservative-free eye-drops formulation for the symptomatic treatment of allergic conjunctivitis. METHODS: This phase 3, multicenter, double-masked, randomized study evaluated the efficacy, safety and tolerability of bilastine 0.6% ophthalmic solution compared to ketotifen 0.025% and vehicle. The primary efficacy endpoint was ocular itching reduction. The Ora-CAC® Allergen Challenge Model was used to assess ocular and nasal symptoms at 15 minutes (onset of action) and 16 hours post-treatment. RESULTS: Subjects (N=228) were 59.6% male, and the mean (SD) age was 44.1 (13.4) years. Bilastine demonstrated efficacy in reducing ocular itching compared to vehicle at both onset of action and 16 hours post-treatment (P <0.001). Ketotifen showed improvement compared to vehicle 15 minutes post-treatment (P <0.001). Bilastine demonstrated statistical non-inferiority to ketotifen for all 3 post-CAC timepoints at 15 minutes post-instillation, based on an inferiority margin of 0.4. Bilastine demonstrated improvement over vehicle (P <0.05) for conjunctival redness, ciliary redness, episcleral redness, chemosis, eyelid swelling, tearing, rhinorrhea, ear and palate pruritus and nasal congestion at 15 minutes post-treatment. Ophthalmic bilastine was safe and well tolerated. Mean drop comfort scores were significantly better (P <0.05) for bilastine compared with ketotifen immediately upon instillation, and similar compared with vehicle. CONCLUSIONS: Ophthalmic bilastine effectively reduced ocular itching for 16 hours post-treatment, suggesting that it could be used as a once-daily treatment for the signs and symptoms of allergic conjunctivitis. ClinicalTrials.gov identifier: NCT03479307.

Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development.

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.

Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study.

BACKGROUND AND OBJECTIVE: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. METHODS: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. RESULTS: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. CONCLUSION: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated.

Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study

Background and objectives: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. Methods: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. Results: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. Conclusions: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated (AU)

Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts / Efeito citotóxico do extrato aquoso de folhas de Vernonanthura polyanthes

Abstract Vernonanthura polyanthes, popularly known as assa-peixe, is a medicinal plant that has been widely used by Brazilian Cerrado population for treatment of diseases without a detailed evaluation of their effectiveness, toxicity, and proper dosage. Thus, more studies investigating the safety of V. polyanthes aqueous extract before the use are needed. The purpose of this study was to evaluate the toxicity, cytotoxicity and genotoxicity of V. polyanthes leaves aqueous extract using the Artemia salina and Allium cepa assays. For the A. salina assay, three groups of 10 larvae were exposed to V. polyanthes leaves aqueous extract at the concentrations of 5, 10, 20, 40, and 80 mg/ml. For the A. cepa assay, 5 onion bulbs were exposed to V. polyanthes leaves aqueous extract at 10, 20, and 40 mg/ml, and then submitted to macroscopic and microscopic analysis. As result it was identified a toxicity and cytotoxicity of V. polyanthes dependent on the extract concentration. The A. salina assay suggests that the concentration of 24 mg/ml of the V. polyanthes extract is able to kill 50% of naupllis; while the A. cepa assay suggests that V. polyanthes leaves aqueous extract is toxic at concentrations higher than 20 mg/ml; however the cytotoxic effect in A. cepa root cells was observed at 40 mg/ml of the extract. It is important to say that the V. polyanthes leaves aqueous extract concentration commonly used in popular medicine is 20 mg/ml. Thus, the popular concentration used is very close to toxicity limit in A. salina model (24 mg/ml) and is the concentration which showed toxic effect in A. cepa root cells (20 mg/ml). No genotoxic activity of V. polyantes leaves aqueous extract was observed in the conditions used in this study. Because of the antiproliferative action and no genotoxic activity, V. polyanthes leaves aqueous extract may present compounds with potential use for human medicine. However more detailed studies need to be performed to confirm this potential.

Resumo Vernonanthura polyanthes, popularmente conhecida como assa-peixe, é uma planta medicinal amplamente utilizada pela população brasileira do Cerrado para o tratamento doenças, sem uma avaliação detalhada de sua eficácia, toxicidade e dosagem adequada. Dessa forma, são necessários estudos para investigar a segurança do uso do extrato aquoso de V. polyanthes. O objetivo deste estudo foi avaliar a toxicidade, citotoxicidade e genotoxicidade do extrato aquoso de folhas de V. polyanthes utilizando os ensaios de Artemia salina e Allium cepa. Para o ensaio de A. salina, três grupos de 10 larvas foram expostos ao extrato aquoso de folhas de V. polyanthes nas concentrações de 5, 10, 20, 40 e 80 mg/ml. Para o ensaio de A. cepa, 5 bulbos de cebola foram expostas ao extrato aquoso de folhas de V. polyanthes nas concentrações de 10, 20 e 40 mg/ml, e então submetidos a análise macroscópica e microscópica. O ensaio de A. salina sugere que a concentração de 24 mg/ml do extrato de V. polyanthes é capaz de matar 50% dos náuplios; enquanto o ensaio de A. cepa sugere que o extrato aquoso das folhas de V. polyanthes é tóxico em concentrações superiores a 20 mg/ml. O efeito citotóxico nas células da raiz de A. cepa foi observado apenas na concentração de 40 mg/ml. É importante dizer que a concentração de extrato aquoso de folhas de V. polyanthes comumente usada na medicina popular é de 20 mg/ml. Assim, a concentração popular utilizada está muito próxima do limite de toxicidade no modelo de A. salina (24 mg/ml) e é a mesma concentração que apresentou efeito tóxico nas células da raiz de A. cepa (20 mg/ml). Não foi observada atividade genotóxica do extrato aquoso de folhas de V. polyantes nas condições utilizadas neste trabalho. Por causa da ação antiproliferativa e ausência de atividade genotóxica, o extrato aquoso de folhas de V. polyanthes pode ser uma boa fonte natural de compostos antitumorais e pode apresentar potencial para uso na medicina. No entanto, estudos mais detalhados precisam ser realizados para confirmar esse potencial.

Electron-phonon coupling enhancement and displacive magnetostructural transition in SrCr2 As2 under magneto-Raman spectroscopy.

A Raman spectroscopy study on high quality single crystals of SrCr2 As2 (SCA) in the temperature T range 4 K < T < 300 K and high applied magnetic fields up to H = 9 T is presented. The chromium B 1g phonon analysis reveals two anomalous shifts in the frequency, the first below T = 250 K at H = 0 T in the saturated AFM G-type order likely due to an enhanced electron-phonon coupling by the magnetic order, whereas the second anomaly occurs above H = 4 T at T = 4 K likely as a consequence of a magnetostructural displacive transition. Renormalization of the electronic Raman spectra in both studies reveals a decrease in the electronic density of states with decreasing T and increasing H, respectively, with consequent changes in the Fermi surface, which are intrinsically related to the observed anomalies.

Lactation curve model with explicit representation of perturbations as a phenotyping tool for dairy livestock precision farming.

In the context of dairy farming, ruminant females often face challenges inducing perturbations that affect their performance and welfare. A key issue is how to assess the effect of perturbations and provide metrics to quantify how animals cope with their environment. Milk production dynamics are good candidates to address this issue: i) they are easily accessible, ii) overall dynamics throughout lactation process are well described and iii) perturbations are visible through milk losses. In this study, a perturbed lactation model (PLM) with explicit representation of perturbations was developed. The model combines two components: i) the unperturbed lactation model that describes a theoretical lactation curve, assumed to reflect female production potential and ii) the perturbation model that describes all the deviations from the unperturbed lactation model with four parameters: starting date, intensity and shape (collapse and recovery). To illustrate the use of the PLM as a phenotyping tool, it was fitted on a data set of 319 complete lactations from 181 individual dairy goats. A total of 2 354 perturbations were detected, with an average of 7.40 perturbations per lactation. Loss of milk production for the whole lactation due to perturbations varied between 2 and 19% of the milk production predicted by the unperturbed lactation model. The number of perturbations was not the major factor explaining the loss of milk production, suggesting that there are different types of animal response to challenges. By incorporating explicit representation of perturbations in a lactation model, it was possible to determine for each female the potential milk production, characteristics of each perturbation and milk losses induced by perturbations. Further, it was possible to compare animals and analyze individual variability. The indicators produced by the PLM are likely to be useful to move from raw data to decision support tools in dairy production.

Do basic auscultation skills need to be resuscitated? A new strategy for improving competency among nursing students.

BACKGROUND: Auscultation of heart and lung sounds is a foundational competency for Registered Nurses (RNs). Precise and timely assessments are important for the early detection and recognition of the deteriorating patient. Studies have shown that improved teaching methods that incorporate emerging technologies and address different learning styles are needed to improve competency in auscultation. METHOD: Undergraduate nursing students (n = 127) were randomized into treatment and control groups. The control group received the usual preparation in auscultation learning strategies. The treatment group received the usual training plus three auscultation learning sessions that were each 2 h in length (cardiac, pulmonary and mixed sounds). RESULTS: The virtual auscultation teaching strategy had a significant impact on undergraduate nursing student's competency in recognizing heart murmurs. The treatment group also had increased scores compared to the control group increased scores in distinguishing normal versus abnormal heart and lung sounds, identification of crackles and diminished breath sounds. CONCLUSION: Virtual auscultation as a teaching strategy was shown to have a positive impact on undergraduate student nurse competence in accurately identifying heart and lung sounds.

Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts.

Vernonanthura polyanthes, popularly known as assa-peixe, is a medicinal plant that has been widely used by Brazilian Cerrado population for treatment of diseases without a detailed evaluation of their effectiveness, toxicity, and proper dosage. Thus, more studies investigating the safety of V. polyanthes aqueous extract before the use are needed. The purpose of this study was to evaluate the toxicity, cytotoxicity and genotoxicity of V. polyanthes leaves aqueous extract using the Artemia salina and Allium cepa assays. For the A. salina assay, three groups of 10 larvae were exposed to V. polyanthes leaves aqueous extract at the concentrations of 5, 10, 20, 40, and 80 mg/ml. For the A. cepa assay, 5 onion bulbs were exposed to V. polyanthes leaves aqueous extract at 10, 20, and 40 mg/ml, and then submitted to macroscopic and microscopic analysis. As result it was identified a toxicity and cytotoxicity of V. polyanthes dependent on the extract concentration. The A. salina assay suggests that the concentration of 24 mg/ml of the V. polyanthes extract is able to kill 50% of naupllis; while the A. cepa assay suggests that V. polyanthes leaves aqueous extract is toxic at concentrations higher than 20 mg/ml; however the cytotoxic effect in A. cepa root cells was observed at 40 mg/ml of the extract. It is important to say that the V. polyanthes leaves aqueous extract concentration commonly used in popular medicine is 20 mg/ml. Thus, the popular concentration used is very close to toxicity limit in A. salina model (24 mg/ml) and is the concentration which showed toxic effect in A. cepa root cells (20 mg/ml). No genotoxic activity of V. polyantes leaves aqueous extract was observed in the conditions used in this study. Because of the antiproliferative action and no genotoxic activity, V. polyanthes leaves aqueous extract may present compounds with potential use for human medicine. However more detailed studies need to be performed to confirm this potential.

Anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide in mice.

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.

Design of a Multipoint Cost-Effective Optical Instrument for Continuous In-Situ Monitoring of Turbidity and Sediment.

A cost-effective optical instrument for continuous in-situ monitoring applications is presented. With a production cost in raw materials of 38 €, a power consumption of 300 A in sleep mode and 100 mA in active mode (5 ms reading), and a capacity to monitor turbidity and sedimentary displacement at eight different depths in the water column, the sensor was developed for sediment monitoring in coastal areas. Due to the extent and dynamics of the processes involved in these areas, observations require a wide spatial and temporal resolution. Each of the eight monitoring nodes uses one infrared backscatter channel, to estimate turbidity and sediment concentration, and one ultraviolet with one infrared transmitted light channels to distinguish organic/inorganic composition of the suspended material load. An in-lab calibration was conducted, using formazine to correlate turbidity with the electronic outputs of the instrument. An analysis of the influence of external light sources and correction techniques were performed. Moreover, an in-lab experiment was conducted to study the behaviour of the sensor-to-sediment transport, wash load and sediment accumulation. The device was deployed, with a water level sensor, in an estuarine area with high sediment dynamics. The monitoring data were analysed, showing the potential of the device to continuously monitor turbidity, sediment processes, and distinguish between organic and inorganic matter, at the different depths in the water column.

Ecosystem Services Provided by Insects in Brazil: What Do We Really Know?

Insects are the most abundant and diverse organisms on Earth and provide essential ecosystem services. However, Brazilian society rarely consider the importance of insects in their diverse country. Therefore, in this review, we provide an overview of ecosystem services provided by insects in Brazil. A database search returned 136 articles, published in English or Portuguese, on ecosystem services provided by insects in Brazil. The first article was published in 1982, and majority of the studies were conducted in the Atlantic Forest or the Cerrado biomes. The most frequently studied insect-provided ecosystem services were pollination, decomposition, and biological control of pests. The studies focused primarily on natural and anthropic ecosystems, and most followed an experimental approach. We noted that the term "ecosystem services" was not used frequently in studies on insects in Brazil. The information available was mostly taxon-biased. We discuss the implications of these findings in relation to reconciling economic interests and the need for insect conservation for continued provision of ecosystem services in a broader perspective. In conclusion, we argue that the scientific community should focus on understanding the ecosystem services provided by insects other than those strictly related to economic activities, and on improving communication with policymakers and citizens. As a tropical and megadiverse country, Brazil has the potential to become a protagonist in conserving and using the ecosystem services provided by insects, both locally and internationally, by providing scientific information to policymakers and citizens.

Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.

Anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide in mice

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.

Development of a Cost-Effective Optical Sensor for Continuous Monitoring of Turbidity and Suspended Particulate Matter in Marine Environment.

A cost-effective optical sensor for continuous in-situ monitoring of turbidity and suspended particulate matter concentration (SPM), with a production cost in raw materials less than 20 €, is presented for marine or fluvial applications. The sensor uses an infrared LED and three photodetectors with three different positions related to the light source-135º, 90º and 0º-resulting in three different types of light detection: backscattering, nephelometry and transmitted light, respectively. This design allows monitoring in any type of environment, offering a wide dynamic range and accuracy for low and high turbidity or SPM values. An ultraviolet emitter-receiver pair is also used to differentiate organic and inorganic matter through the differences in absorption at different wavelengths. The optical transducers are built in a watertight structure with a radial configuration where a printed circuit board with the electronic signal coupling is assembled. An in-lab calibration of the sensor was made to establish a relation between suspended particulate matter (SPM) or the turbidity (NTU) to the photodetectors' electrical output value in Volts. Two different sizes of seashore sand were used (180 µm and 350 µm) to evaluate the particle size susceptibility. The sensor was tested in a fluvial environment to evaluate SPM change during sediment transport caused by rain, and a real test of 22 days continuous in-situ monitoring was realized to evaluate its performance in a tidal area. The monitoring results were analysed, showing the SPM change during tidal cycles as well as the influence of the external light and biofouling problems.

Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regeneration.

Ceramic/polymer-based biocomposites have emerged as potential biomaterials to fill, replace, repair or regenerate injured or diseased bone, due to their outstanding features in terms of biocompatibility, bioactivity, injectability, and biodegradability. However, these properties can be dependent on the amount of ceramic component present in the polymer-based composite. Therefore, in the present study, the influence of nanohydroxyapatite content (30 to 70 wt%) on alginate-based hydrogels was studied in order to evaluate the best formulation for maximizing bone tissue regeneration. The composite system was characterized in terms of physic-chemical properties and biological response, with in vitro cytocompatibility assessment with human osteoblastic cells and ex vivo functional evaluation in embryonic chick segmental bone defects. The main morphological characteristics of the alginate network were not affected by the addition of nanohydroxyapatite. However, physic-chemical features, like water-swelling rate, stability at extreme pH values, apatite formation, and Ca2+ release were nanoHA dose-dependent. Within in vitro cytocompatibility assays it was observed that hydrogels with nanoHA 30% content enhanced osteoblastic cells proliferation and expression of osteogenic transcription factors, while those with higher concentrations (50 and 70%) decreased the osteogenic cell response. Ex vivo data underlined the in vitro findings, revealing an enhanced collagenous deposition, trabecular bone formation and matrix mineralization with Alg-nanoHA30 composition, while compositions with higher nanoHA content induced a diminished bone tissue response. The outcomes of this study indicate that nanohydroxyapatite concentration plays a major role in physic-chemical properties and biological response of the composite system and the optimization of the components ratio must be met to maximize bone tissue regeneration.

Remote Ischemic Preconditioning Is Efficient in Reducing Hepatic Ischemia-Reperfusion Injury in a Growing Rat Model and Does Not Promote Histologic Lesions in Distant Organs.

OBJECTIVE: Ischemic preconditioning (IPC) was developed to diminish ischemia-reperfusion injury (IRI). There are two main ways of performing it: direct ischemic-preconditioning (DIP) and remote ischemic-preconditioning (RIP). The objectives of this study were to investigate local and systemic effects of DIP and RIP in liver IRI. METHODS: Thirty-two weaning rats (50-70 g body weight; 21 days old) were divided into 4 groups: control (C); ischemia followed by reperfusion (IR); DIP followed by ischemia and reperfusion; and RIP followed by ischemia and reperfusion. In the IR group, the vascular pedicles of medial and left lateral liver lobes were clamped for 60 minutes and then unclamped. In the DIP group, a 10-minute cycle of ischemia followed by a 10-minute reperfusion of the same lobes was performed before 60 minutes of ischemia. In the RIP group, three 5-minute cycles of clamping and unclamping of the femoral vessels were performed before liver ischemia. The animals were euthanized 24 hours after the surgical procedures. RESULTS: The serum levels of liver enzymes were significantly lower in the RIP group compared to the control and IR groups and to the DIP group. The scores of histologic hepatic lesions were significantly lower in RIP animals than those of IR animals (P = .002) and similar to the C group animals. The Bax/BCl-xl relation was lower in the DIP group than that in the RIP group (P = .045) and no differences were observed in histologic analyses of kidney, lung, intestine, and heart. CONCLUSION: In young animals, the beneficial effects of RIP are more evident than those of DIP.

Whole-Body Vibration Does Not Seem to Affect Postural Control in Healthy Active Older Women.

OBJECTIVE: This study investigated the acute residual effects induced by different frequencies of whole-body vibration (WBV) on postural control of elderly women. DESIGN: Thirty physically active elderly women (67 ± 5 years) were randomly divided into three groups: two experimental groups (high WBV frequency: 45 Hz and 4 mm amplitude, n = 10; low WBV frequency: 30 Hz and 4 mm amplitude, n = 10) and one control group (n = 10), with no treatment. The participants were first subjected to stabilometry tests and were then guided through three sets of isometric partial squats for 60 s while the WBV stimulation was applied. The control group was subjected to the same conditions but without the WBV stimulation. The participants were again subjected to body balance tests immediately following the end of the intervention period and again at 8, 16, and 24 min. To measure body sway control, three 60 s tests were performed at 10 s intervals for each of the following experimental conditions: (1) eyes opened and (2) eyes closed. The following variables were investigated: the average velocity of the displacement of the centre of pressure in the anterior-posterior and medial-lateral planes as well as in the elliptical area. RESULTS: A 3 (condition) × 5 (test) two-way repeated-measures ANOVA did not identify significant differences in the stabilometric variables, regardless of group, time, or experimental condition. CONCLUSIONS: The effect of WBV, regardless of the stimulation frequency, did not have a significant effect immediately after or up to 24 minutes after vibration cessation, on the variables involved in the control of postural stability in physically active elderly women.