Electron ionization induced fragmentation pathways of trichloroanisole.

Trichloroanisole (TCA) is one of the most significant contaminants in cork stoppers. The presence of TCA leads to an unpleasant odor known as "cork taint", resulting in high economic losses for the cork and wine industries. Hence, the detection, quantification, and characterization of TCA are essential to address this concern. The present study investigates the electron-driven fragmentation pathways of TCA through electron ionization mass spectrometry as a function of electron energy (0-100 eV), and the results are supported by theoretical characterization of ionization potentials, dissociation thresholds, and electron ionization cross sections. The appearance energies of ten cations were measured, including the first experimental evaluation of the molecule's ionization energy at 8.8 ± 0.3 eV, in excellent agreement with the calculations (8.83 eV). For lower energies, around 20 eV, the parent cation accounted for more than 60% of the total ion signal, followed by its demethylated fragment. Taken together, these ion signals could be used as fingerprints of TCA in industrial quality control by low-energy electron ionization mass spectrometry. Fifty other fragments have been identified at higher electron energies, revealing the very rich fragmentation pattern of TCA.

Boroxine benzaldehyde complex for pharmaceutical applications probed by electron interactions.

RATIONALE: 2,4,6-Tris(4-formylphenyl)boroxine (TFPB) is a substituted boroxine containing a benzaldehyde molecule bonded to each boron atom. Boroxine cages are an emerging class of functional nanostructures used in host-guest chemistry, and benzaldehyde is a potential radiosensitizer. Reactions initiated by low-energy electrons with such complexes may dictate and bring new fundamental knowledge for biomedical and pharmaceutical applications. METHODS: The electron ionization properties of TFPB are investigated using a gas-phase electron-molecule crossed beam apparatus coupled with a reflectron time-of-flight mass spectrometer in an orthogonal geometry. Ionization and threshold energies are experimentally determined by mass spectra acquisition as a function of the electron energy. RESULTS: The abundance of the molecular precursor cation in the mass spectrum at 70 eV is significantly lower than that of the most abundant fragment C7 H5 O+ . Twenty-nine cationic fragments with relative intensities >2% are detected and identified. The appearance energies of six fragment cations are reported, and the experimental first ionization potential is found at 9.46 ± 0.11  eV. Moreover, eight double cations are identified. The present results are supported by quantum chemical calculations based on bound state techniques, electron ionization models and thermodynamic thresholds. CONCLUSIONS: According to these results, the TPFB properties may combine the potential radiosensitizer effect of benzaldehyde with the stability of the boroxine ring.

Total Electron Detachment and Induced Cationic Fragmentation Cross Sections for Superoxide Anion (O2-) Collisions with Benzene (C6H6) Molecules.

In this study, novel experimental total electron detachment cross sections for O2- collisions with benzene molecules are reported for the impact energy range (10-1000 eV), as measured with a transmission beam apparatus. By analysing the positively charged species produced during the collision events, relative total ionisation cross sections were derived in the incident energy range of 160-900 eV. Relative partial ionisation cross sections for fragments with m/z ≤ 78 u were also given in this energy range. We also confirmed that heavier compounds (m/z > 78 u) formed for impact energies between 550 and 800 eV. In order to further our knowledge about the collision dynamics governing the fragmentation of such heavier molecular compounds, we performed molecular dynamics calculations within the framework of the Density Functional Theory (DFT). These results demonstrated that the fragmentation of these heavier compounds strongly supports the experimental evidence of m/z = 39-42, 50, 60 (u) cations formation, which contributed to the broad local maximum in the total ionisation observed from 550 to 800 eV. This work reveals the reactivity induced by molecular anions colliding with hydrocarbons at high energies, processes that can take place in the interstellar medium under various local conditions.

Unexpected benzene oxidation in collisions with superoxide anions.

Superoxide anions colliding with benzene molecules at impact energies from 200 to 900 eV are reported for the first time to form massive complexes. With the aid of quantum chemistry calculations, we propose a mechanism in which a sudden double ionization of benzene and the subsequent electrostatic attraction between the dication and the anion form a stable covalently bonded C6H6O2+ molecule, that evolves towards the formation of benzene-diol conformers. These findings lend support to a model presenting a new high energy anion-driven chemistry as an alternative way to form complex molecules.

Excited States of Bromopyrimidines Probed by VUV Photoabsorption Spectroscopy and Theoretical Calculations.

We report absolute photoabsorption cross sections for gas-phase 2- and 5-bromopyrimidine in the 3.7-10.8 eV energy range, in a joint theoretical and experimental study. The measurements were carried out using high-resolution vacuum ultraviolet synchrotron radiation, with quantum chemical calculations performed through the nuclear ensemble approach in combination with time-dependent density functional theory, along with additional Franck-Condon Herzberg-Teller calculations for the first absorption band (3.7-4.6 eV). The cross sections of both bromopyrimidines are very similar below 7.3 eV, deviating more substantially from each other at higher energies. In the 7.3-9.0 eV range where the maximum cross-section is found, a single and broad band is observed for 5-bromopyrimidine, while more discernible features appear in the case of 2-bromopyrimidine. Several π* ← π transitions account for the most intense bands, while weaker ones are assigned to transitions involving the nitrogen and bromine lone pairs, the antibonding σ*Br orbital, and the lower-lying Rydberg states. A detailed comparison with the available photo-absorption data of bromobenzene is also reported. We have found significant differences regarding the main absorption band, which is more peaked in bromobenzene, becoming broader and shifting to higher energies in both bromopyrimidines. In addition, there is a significant suppression of vibrational structures and of Rydberg states in the pair of isomers, most noticeably for 2-bromopyrimidine.

Promoção da Literacia em Saúde sobre Diabetes Mellitus aos idosos / Promotion of Health Literacy on Diabetes Mellitus to the elderly

A Diabetes Mellitus é uma doença crónica, cuja prevalência tem aumentado de forma significativa na população idosa, causando elevada mortalidade a nível mundial. Os enfermeiros através da promoção da literacia em saúde podem capacitar os indivíduos a prevenir e a gerir a sua situação de saúde. Desenvolveu-se uma Scoping Review, com a questão: quais as intervenções de enfermagem na promoção da literacia em saúde sobre Diabetes Mellitus aos idosos? Nas evidências obtidas identificou-se a importância das intervenções educativas dos enfermeiros na prevenção e controlo da diabetes nos idosos. Tendo como base a metodologia do Planeamento em Saúde, foi elaborado o projeto de intervenção comunitária "Diabetes no Saka", com o objetivo de promover a literacia em saúde na prevenção da Diabetes e suas complicações nos idosos com 65 ou mais anos, residentes num bairro social. Os resultados apontam para uma taxa de conhecimentos adquiridos igual ou superior a 98%, demonstrando o impacto positivo do projeto.

Diabetes Mellitus is a chronic disease whose prevalence has increased significantly in the elderly population, causing high mortality worldwide. Nurses by promoting health literacy can empower individuals to prevent and manage their health situation. A Scoping Review was developed, with the question: what are the nursing interventions in promoting health literacy on Diabetes Mellitus for the elderly? The evidence obtained identified the importance of nurses' educational interventions in the prevention and control of diabetes in the elderly. Based on the Methodology of Health Planning, the community intervention project "Diabetes in Saka" was elaborated, with the objective of promoting health literacy in the prevention of diabetes and its complications in the elderly aged 65 years or older, living in a social neighborhood. The results point to a rate of acquired knowledge equal to or greater than 98%, demonstrating the positive impact of the project.

Electron Driven Reactions in Tetrafluoroethane: Positive and Negative Ion Formation.

In the search for alternatives to chlorine-containing gases, tetrafluoroethane, CF3CH2F (R134a), a widely used refrigerant gas, has been recognized as a promising substitute for dichlorodifluoromethane, CCl2F2 (R12). When R12 is replaced by R134a, the global warming potential drops from 8100 to 1430, the ozone depletion potential changes from 1 to 0, and the atmospheric lifetime decreases from 100 to 14 years. Electron interactions in the gas phase play a fundamental role in the atmospheric sciences. Here, we present a detailed study on electron-driven fragmentation pathways of CF3CH2F, in which we have investigated processes induced by both electron ionization and electron attachment. The measurements allow us to report the ion efficiency curves for ion formation in the energy range of 0 up to 25 eV. For positive ion formation, R134a dissociates into a wide assortment of ions, in which CF3+ is observed as the most abundant out of seven ions with a relative intensity above 2%. The results are supported by quantum chemical calculations based on bound state techniques, electron-impact ionization models, and electron-molecule scattering simulations, showing a good agreement. Moreover, the experimental first ionization potential was found at 13.10 ± 0.17 eV and the second at around 14.25 eV. For negative ion formation, C2F3- was detected as the only anion formed, above 8.3 eV. This study demonstrates the role of electrons in the dissociation of R134a, which is relevant for an improvement of the refrigeration processes as well as in atmospheric chemistry and plasma sciences.

Single-Arm, Multicenter Phase I/II Clinical Trial for the Treatment of Envenomings by Massive Africanized Honey Bee Stings Using the Unique Apilic Antivenom.

We evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach Africanized honeybee (Apis mellifera) Antivenom (AAV) in a phase I/II, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. Participants received 2 to 10 vials of AAV depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. The primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. Preliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. ELISA assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. Twenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m2 (median = 1.93 m2) were recruited. The number of stings ranged from 7 to > 2,000, with a median of 52.5. Symptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of AAV as per the protocol. None of the patients had late reactions (serum sickness) within 30 d of treatment. There was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. One patient had a moderate adverse event, transient itchy skin, and erythroderma. All participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. ELISA assays showed venom (melittin and PLA2) concentrations varying between 0.25 and 1.479 ng/mL prior to treatment. Venom levels decreased in all patients during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. Mass spectrometry showed melittin in eight participants, 30 d after treatment. Considering the promising safety results for this investigational product in the treatment of massive Africanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the AAV has shown to be safe for human use. Clinical Trial Registration: UTN: U1111-1160-7011, identifier [RBR-3fthf8].

Single-arm, multicenter phase I/II clinical trial for the treatment of envenomings by massive africanized honey bee stings using the unique apilic antivenom

We evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach Africanized honeybee (Apis mellifera) Antivenom (AAV) in a phase I/II, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. Participants received 2 to 10 vials of AAV depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. The primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. Preliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. ELISA assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. Twenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m2 (median = 1.93 m2) were recruited. The number of stings ranged from 7 to > 2,000, with a median of 52.5. Symptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of AAV as per the protocol. None of the patients had late reactions (serum sickness) within 30 d of treatment. There was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. One patient had a moderate adverse event, transient itchy skin, and erythroderma. All participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. ELISA assays showed venom (melittin and PLA2) concentrations varying between 0.25 and 1.479 ng/mL prior to treatment. Venom levels decreased in all patients during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. Mass spectrometry showed melittin in eight participants, 30 d after treatment. Considering the promising safety results for this investigational product in the treatment of massive Africanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the AAV has shown to be safe for human use. Clinical Trial Registration: UTN: U1111-1160-7011, identifier [RBR-3fthf8].

Electron Transfer Induced Decomposition in Potassium-Nitroimidazoles Collisions: An Experimental and Theoretical Work.

Electron transfer induced decomposition mechanism of nitroimidazole and a selection of analogue molecules in collisions with neutral potassium (K) atoms from 10 to 1000 eV have been thoroughly investigated. In this laboratory collision regime, the formation of negative ions was time-of-flight mass analyzed and the fragmentation patterns and branching ratios have been obtained. The most abundant anions have been assigned to the parent molecule and the nitrogen oxide anion (NO2-) and the electron transfer mechanisms are comprehensively discussed. This work focuses on the analysis of all fragment anions produced and it is complementary of our recent work on selective hydrogen loss from the transient negative ions produced in these collisions. Ab initio theoretical calculations were performed for 4-nitroimidazole (4NI), 2-nitroimidazole (2NI), 1-methyl-4- (Me4NI) and 1-methyl-5-nitroimidazole (Me5NI), and imidazole (IMI) in the presence of a potassium atom and provided a strong basis for the assignment of the lowest unoccupied molecular orbitals accessed in the collision process.

The Role of Electron Transfer in the Fragmentation of Phenyl and Cyclohexyl Boronic Acids.

In this study, novel measurements of negative ion formation in neutral potassium-neutral boronic acid collisions are reported in electron transfer experiments. The fragmentation pattern of phenylboronic acid is comprehensively investigated for a wide range of collision energies, i.e., from 10 to 1000 eV in the laboratory frame, allowing some of the most relevant dissociation channels to be probed. These studies were performed in a crossed molecular beam set up using a potassium atom as an electron donor. The negative ions formed in the collision region were mass analysed with a reflectron time-of-flight mass spectrometer. In the unimolecular decomposition of the temporary negative ion, the two most relevant yields were assigned to BO- and BO2-. Moreover, the collision-induced reaction was shown to be selective, i.e., at energies below 100 eV, it mostly formed BO-, while at energies above 100 eV, it mostly formed BO2-. In order to further our knowledge on the complex internal reaction mechanisms underlying the influence of the hybridization state of the boron atom, cyclohexylboronic acid was also investigated in the same collision energy range, where the main dissociation channel yielded BO2-. The experimental results for phenyl boronic acid are supported by ab initio theoretical calculations of the lowest unoccupied molecular orbitals (LUMOs) accessed in the collision process.

Ion-Pair Formation in Neutral Potassium-Neutral Pyrimidine Collisions: Electron Transfer Experiments.

We report novel data on ion-pair formation in hyperthermal (30-800 eV) neutral potassium collisions with neutral pyrimidine (Pyr, C4H4N2) molecules. In this collision regime, negative ions formed by electron transfer from the alkali atom to the target molecule were time-of-flight mass analyzed and the fragmentation patterns and branching ratios have been obtained. The most abundant product anions have been assigned to CN- and C2H- and the electron transfer mechanisms are comprehensively discussed. Particular importance is also given to the efficient loss of integrity of the pyrimidine ring in the presence of an extra electron, which is in contrast to dissociative electron attachment experiments yielding the dehydrogenated parent anion. Theoretical calculations were performed for pyrimidine in the presence of a potassium atom and provided a strong basis for the assignment of the lowest unoccupied molecular orbitals accessed in the collision process. In order to further our knowledge about the collision dynamics, potassium cation (K+) energy loss spectrum has been obtained and within this context, we also discuss the role of the accessible electronic states. A vertical electron affinity of (-5.69 ± 0.20) eV was obtained and may be assigned to a π 3 * (b 1) state that leads to CN- formation.

Asymptomatic HIV People Present Different Profiles of sCD14, sRAGE, DNA Damage, and Vitamins, according to the Use of cART and CD4+ T Cell Restoration.

We aimed to analyze markers of immune activation, inflammation, and oxidative stress in 92 asymptomatic HIV-infected patients according to the adequate (AR, >500 cells/mm3) or inadequate (IR, <500 cells/mm3) CD4+ T recovery and the presence or absence of antiretroviral treatment (cART). In relation to those newly diagnosed, they were divided into two groups, cART-naïve IR (nIR) and cART-naïve AR (nAR). Among those diagnosed more than five years ago, the following division was made: the cART-naïve long-term nonprogressors (LTNP); patient under cART and AR (tAR); and patients under cART and IR (tIR). We investigated the expression of soluble receptor for advanced glycation end products (sRAGE), high-mobility group-box protein -1 (HMGB1), soluble CD14 (sCD14), IL-8, IL-10, 8-isoprostane, vitamins, and DNA damage. We observed higher levels of sRAGE in tAR as compared to nIR, nAR, LTNP, and more sCD14 than in nIR and nAR. As for IL-10 levels, we found nIR > nAR > LTNP > tAR > tIR. Higher levels of 8-isoprostane were observed in nIR. LTNP presented a higher retinol dosage than tAR and less genotoxic damage induced by oxidative stress than the other groups. We suggest that the therapy, despite being related to lesser immune activation and inflammation, alters the vitamin profile and consequently increases the oxidative stress of patients. In addition, the lowest genotoxic index for LTNP indicates that both VL and cART could be responsible for the increased DNA damage. More studies are needed to understand the influence of cART on persistent immune activation and inflammation.

Appropriating Video Surveillance for Art and Environmental Awareness: Experiences from ARTiVIS.

Arts, Real-Time Video and Interactivity for Sustainability (ARTiVIS) is an ongoing collaborative research project investigating how real-time video, DIY surveillance technologies and sensor data can be used as a tool for environmental awareness, activism and artistic explorations. The project consists of a series of digital contexts for aesthetic contemplation of nature and civic engagement, aiming to foster awareness and empowerment of local populations through DIY surveillance. At the core of the ARTIVIS efforts are a series of interactive installations (namely B-Wind!, Hug@tree and Play with Fire), that make use of surveillance technologies and real-time video as raw material to promote environmental awareness through the emotion generated by real-time connections with nature. Throughout the project development, the surveillance concept has been shifting from the use of surveillance technology in a centralized platform, to the idea of veillance with distributed peer-to-peer networks that can be used for science and environmental monitoring. In this paper we present the history of the ARTiVIS project, related and inspiring work, describe ongoing research work and explore the present and future challenges of appropriating surveillance technology for artistic, educational and civic engagement purposes.

Comprehensive investigation of the electronic excitation of W(CO)6 by photoabsorption and theoretical analysis in the energy region from 3.9 to 10.8 eV.

High-resolution vacuum ultraviolet photoabsorption measurements in the wavelength range of 115-320 nm (10.8-3.9 eV) have been performed together with comprehensive relativistic time-dependent density functional calculations (TDDFT) on the low-lying excited sates of tungsten hexacarbonyl, W(CO)6. The higher resolution obtained reveals previously unresolved spectral features of W(CO)6. The spectrum shows two higher-energy bands (in the energy ranges of 7.22-8.12 eV and 8.15-9.05 eV), one of them with clear vibrational structure, and a few lower-energy shoulders in addition to a couple of lower-energy metal-to-ligand charge-transfer (MLCT) bands reported in the literature before. Absolute photoabsorption cross sections are reported and, where possible, compared to previously published results. On the basis of this combined experimental/theoretical study the absorption spectrum of the complex has been totally re-assigned between 3.9 and 10.8 eV under the light of spin-orbit coupling (SOC) effects. The present comprehensive knowledge of the nature of the electronically excited states may be of relevance to estimate neutral dissociation cross sections of W(CO)6, a precursor molecule in focused electron beam induced deposition (FEBID) processes, from electron scattering measurements.

"Jogo da postura": programa de intervenção de enfermagem em crianças / "Juego de la postura": programa de intervención de enfermería en niños / "Posture Play": A Nursing Intervention Program for Children

RESUMO Objetivo: evidenciar o impacto de um jogo para promover a educação postural das crianças. O enfermeiro tem um papel preponderante na educação para a saúde, pelo que procuramos um caminho que adicionasse alguma inovação às Escolas Posturais já existentes incorporando uma estratégia formativa inovadora: "um jogo". Materiais e método: trata-se de um estudo quase experimental com delineamento de tempo. A amostra é constituída por 215 crianças do ensino pré-escolar e do 1º ciclo do ensino básico, de uma cidade do norte de Portugal. A intervenção é composta pela aplicação de um jogo intitulado "Jogo da postura"; para avaliar o seu impacto, foi aplicado um questionário sobre hábitos posturais antes e após a intervenção. Resultados: os resultados evidenciam uma elevada prevalência de queixas músculo-esqueléticas (48,8 %) e um aumento de respostas corretas após a intervenção. Houve mudança no conhecimento de hábitos posturais antes da participação dos alunos num programa de educação postural e depois dela. Conclusões: o jogo é uma estratégia ativa útil e eficaz a ser utilizada pelos formadores no âmbito da enfermagem e deve ser replicada a outras áreas temáticas.

RESUMEN Objetivo: evidenciar el impacto de un juego para impulsar la educación postural de los niños. El enfermero tiene un rol preponderante en la educación para la salud, por lo cual buscamos un camino que les agregara alguna innovación a las escuelas posturales ya existentes incorporando una estrategia formativa novedosa: "un juego". Materiales y método: estudio casi experimental con delineamiento de tiempo. La muestra se constituye de 215 niños del preescolar y el 1º ciclo de la enseñanza básica, de una ciudad del norte de Portugal. La intervención se realiza por medio de la aplicación del "Juego de la postura"; para evaluar su impacto, se administró un cuestionario sobre hábitos posturales antes y después de la intervención. Resultados: los resultados dan cuenta de una elevada prevalencia de quejas músculo-esqueléticas (48,8 %) y un incremento de respuestas correctas tras la intervención. Hubo cambio en el conocimiento de hábitos posturales antes de la participación de los alumnos en un programa de educación postural y luego de ella. Conclusiones: el juego es una estrategia activa útil y eficaz, que puede ser utilizada por los formadores en el contexto de la enfermería y debe replicarse a otras áreas temáticas.

ABSTRACT Objective: demonstrate the impact of a game to help teach children to be mindful of their posture. Nurses have a preeminent role in health education; hence, the importance of finding a way for them to add innovation to the posture schools that already exist, by including a novel training strategy: "a game." Materials and method: This is a quasi-experimental study with a time line. The sample was comprised of 215 pre-school children and first-graders [RD1] in a city in northern Portugal. The intervention was carried out through a game known as Posture Play, and a questionnaire was administered before and afterwards to assess its impact. Results: The results show a high prevalence of musculoskeletal complaints (48.8%) and an increase in correct responses subsequent to the intervention. There was a change in what the students knew about posture and their posture habits before and after taking part in the posture education program. Conclusions: Play is a useful and effective strategy educators can use in the context of nursing and should be replicated to other subject areas.

A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom.

BACKGROUND: Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. METHODS: In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. RESULTS: This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research - CONEP) and sanitation (National Health Surveillance Agency - ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. CONCLUSIONS: This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.

A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom

Background Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A2, cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. Methods In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. Results This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research - CONEP) and sanitation (National Health Surveillance Agency - ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. Conclusions This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera. The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.(AU)