Amphibian tolerance to arsenic: microbiome-mediated insights.

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure.

A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.

Does Parity Influence the Magnitude of the Stress Response of Nellore Cows at Weaning?

Most studies investigate the impact of stress at weaning on calves; however, little is known about the responses of cows, and whether they would differ according to parity. This study aims to investigate whether parity would influence the weaning stress response in beef cows. Thirty pregnant Nellore cows with their respective calves were randomly allocated to five paddocks and two females from each parity group were placed in the paddocks. There was an interaction (p < 0.05) between parity and evaluation days regarding cortisol, where on d + 7, the higher concentration was observed for multiparous cows. There was an interaction (p < 0.05) between parity and evaluation day for red blood cells (RBC), hematocrit (HCT), and hemoglobin (HB), whereby higher RBC counts on d + 4 were observed for multiparous cows. For HCT and HB, on all post-weaning collection days, higher values were observed for multiparous cows. The day of evaluation had an (p < 0.05) effect on all recorded behaviors, except for rumination (p > 0.05). Nellore cows, regardless of parity, underwent behavioral and physiological changes on abrupt weaning. Physiological parameters indicated that the magnitude of stress was greater in multiparous cows.

Accelerated synthesis of phthalimide derivatives: Intrinsic reactivity of diamines towards phthalic anhydride evaluated by paper spray ionization mass spectrometry.

RATIONALE: Paper spray (PS) is a simple and innovative ambient ionization technique for mass spectrometry (MS) analysis. Under PS-MS conditions, chemical reactions, which usually occur slowly on a bulk scale, are accelerated. Moreover, the formation of products and transient species can be easily monitored. In this manuscript, reactions between phthalic anhydride and diamines were conducted and monitored using a PS-MS platform. The reaction products (phthalimides) have many pharmaceutical applications, but their traditional syntheses can take hours under reflux, requiring laborious purification steps. METHODS: In situ reactions were performed by dropping methanolic solutions of phthalic anhydride and diamines on a triangular paper. The analyses were achieved by positioning the triangle tip in front of the mass spectrometer entrance, whereas a metal clip was attached to the triangle base. After adding methanol to the paper, a high voltage was applied across the metal clip, and the mass spectra were acquired. RESULTS: The intrinsic reactivity of alkyl and aromatic diamines was evaluated. The carbon chain remarkably influenced the reactivity of aliphatic diamines. For aryl diamines, the ortho isomer was the most reactive. Moreover, for aryl amines with electron-withdrawing substituents, no reaction was noticed. CONCLUSIONS: Taking advantage of the unique characteristics of PS-MS, it was possible to investigate the intrinsic reactivity of model alkyl (ethylene versus propylene) and aryl (o-phenylene versus m-phenylene and p-phenylene) diamines towards phthalic anhydride. Some crucial parameters that affect the intrinsic reactivity of organic molecules, such as isomerism, intramolecular interaction, and conformation, were easily explored.

Histological and Immunohistochemical Characteristics for Hereditary Breast Cancer Risk in a Cohort of Brazilian Women.

OBJECTIVE: The study aimed to characterize the clinical, histological, and immunohistochemical profile of women with invasive breast cancer, according to the risk for Hereditary Predisposition Breast and Ovarian Cancer Syndrome in a Brazilian population. METHODS: This is a retrospective study performed from a hospital-based cohort of 522 women, diagnosed with breast cancer treated at an oncology referral center in the Southeast region of Brazil, between 2014 and 2016. RESULTS: Among the 430 women diagnosed with invasive breast cancer who composed the study population, 127 (29.5%) were classified as at increased risk for hereditary predisposition to breast and ovarian cancer syndrome. There was a lower level of education in patients at increased risk (34.6%) when compared with those at usual risk (46.0%). Regarding tumor characteristics, women at increased risk had higher percentages of the disease diagnosed at an advanced stage (32.3%), and with tumors > 2cm (63.0%), with increased prevalence for both characteristics, when compared with those at usual risk. Furthermore, we found higher percentages of HG3 (43.3%) and Ki-67 ≥ 25% (64.6%) in women at increased risk, with prevalence being about twice as high in this group. The presence of triple-negative tumors was observed as 25.2% in women at increased risk and 6.0% in women at usual risk, with the prevalence of absence of biomarkers being 2.5 times higher among women in the increased risk group. CONCLUSION: From the clinical criteria routinely used in the diagnosis of breast cancer, the care practice of genetic counseling for patients at increased risk of hereditary breast cancer in contexts such as Brazil is still scarce.

OBJETIVO: O presente estudo buscou caracterizar o perfil clínico, histológico e imunohistoquímico de mulheres com câncer de mama invasivo segundo o risco para a Síndrome de Predisposição Hereditária ao Câncer de Mama e Ovário em uma população brasileira. MéTODOS: Trata-se de um estudo retrospectivo realizado a partir de uma coorte hospitalar composta por 522 mulheres diagnosticadas com câncer de mama entre 2014 e 2016 assistidas em um centro de referência oncológica localizado na região sudeste brasileira. RESULTADOS: Entre as 430 mulheres diagnosticadas com câncer de mama invasivo que compuseram a população de estudo, 127 (29,5%) foram classificadas como de risco aumentado para a síndrome de predisposição hereditária ao câncer de mama e ovário. Verificou-se menor nível de escolaridade nas pacientes com risco aumentado (34,6%) quando comparadas àquelas consideradas como de risco habitual (46,0%). Quanto às características do tumor, as mulheres de risco aumentado apresentaram maiores percentuais de doença diagnosticada em estádio avançado (32,3%) e com tumores > 2cm (63,0%), com prevalência aumentada para ambas as características, quando comparadas àquelas de risco habitual. Ainda nas mulheres de risco aumentado, foram encontrados maiores percentuais de GH3 (43,3%) e Ki-67 ≥ 25% (64,6%), com prevalência cerca de duas vezes maior neste grupo. A presença de tumores triplo-negativos foi observada em 25,2% nas mulheres de risco aumentado e 6,0% nas mulheres de risco habitual, com prevalência de ausência de biomarcadores 2,5 vezes maior entre as mulheres do grupo de risco aumentado. CONCLUSãO: A partir dos critérios clínicos rotineiramente utilizados no diagnóstico do câncer de mama, a prática assistencial do aconselhamento genético para as pacientes com risco aumentado de câncer de mama hereditário em contextos como o do Brasil ainda é escarça.

The Importance of Decarbonylation Mechanisms in the Atomic Layer Deposition of High-Quality Ru Films by Zero-Oxidation State Ru(DMBD)(CO)3.

Achieving facile nucleation of noble metal films through atomic layer deposition (ALD) is extremely challenging. To this end, η4 -2,3-dimethylbutadiene ruthenium(0) tricarbonyl (Ru(DMBD)(CO)3 ), a zero-valent complex, has recently been reported to achieve good nucleation by ALD at relatively low temperatures and mild reaction conditions. The authors study the growth mechanism of this precursor by in situ quartz-crystal microbalance and quadrupole mass spectrometry during Ru ALD, complemented by ex situ film characterization and kinetic modeling. These studies reveal that Ru(DMBD)(CO)3 produces high-quality Ru films with excellent nucleation properties. This results in smooth, coalesced films even at low film thicknesses, all important traits for device applications. However, Ru deposition follows a kinetically limited decarbonylation reaction scheme, akin to typical chemical vapor deposition processes, with a strong dependence on both temperature and reaction timescale. The non-self-limiting nature of the kinetically driven mechanism presents both challenges for ALD implementation and opportunities for process tuning. By surveying reports of similar precursors, it is suggested that the findings can be generalized to the broader class of zero-oxidation state carbonyl-based precursors used in thermal ALD, with insight into the design of effective saturation studies.

Breakthrough Candidemia in Pediatric Patients With Cancer From a Brazilian Center.

We analyzed 19 cases of breakthrough candidemia from a referral pediatric cancer center in Brazil. All patients had neutropenia and were under antifungal prophylactic regimens, mostly micafungin (68%). Most of the patients were treated with amphotericin B formulations and 30-day mortality was 21%. Candida parapsilosis was the main etiologic agent (63%), and horizontal transmission was not evidenced by microsatellite analysis.

Distinguishing legal and illegal cigarettes by applying paper spray mass spectrometry and chemometric tools.

RATIONALE: Smoking is responsible for one in five deaths around the world. Thus, governments have been trying to reduce the number of active smokers by increasing taxes on products. This scenario creates a new problem by raising the consumption of illegally traded cigarettes, which are often seized and analyzed by police forces. METHODS: Legal and illegal cigarette samples were extracted and analyzed using paper spray ionization mass spectrometry (PS-MS). The mass spectrometer was set to operate in full-scan positive ion mode to yield representative chemical profiles of each sample. The results were used to build a chemometric model using partial least squares discriminant analysis (PLS-DA) to discriminate between both sets of samples, i.e. legal and illegal. RESULTS: The PS-MS procedure was fast, simple and efficient, yielding high-quality and reproducible mass spectra with a very good signal-to-noise ratio. Even though all samples displayed visually indistinguishable mass spectra, the PS-MS data handled by the PLS-DA approach furnished a model that reached sample classification with rates of 100% and 80% for the training and validation sets, respectively. CONCLUSIONS: A novel methodology was successfully developed associating the PS-MS technique with chemometric analysis to differentiate between legal and illegal cigarettes. The PS-MS technique proved to be adequate for obtaining fingerprints of such types of samples despite high complexity, and a PLS-DA model was successfully constructed achieving 82.1% accuracy.

Understanding chemical and physical mechanisms in atomic layer deposition.

Atomic layer deposition (ALD) is a powerful tool for achieving atomic level control in the deposition of thin films. However, several physical and chemical phenomena can occur which cause deviation from "ideal" film growth during ALD. Understanding the underlying mechanisms that cause these deviations is important to achieving even better control over the growth of the deposited material. Herein, we review several precursor chemisorption mechanisms and the effect of chemisorption on ALD growth. We then follow with a discussion on diffusion and its impact on film growth during ALD. Together, these two fundamental processes of chemisorption and diffusion underlie the majority of mechanisms which contribute to material growth during a given ALD process, and the recognition of their role allows for more rational design of ALD parameters.

Recognizing drug-facilitated crimes: Detection and quantification of benzodiazepines in beverages using fast liquid-liquid extraction with low temperature partitioning and paper spray mass spectrometry.

A novel methodology using liquid-liquid extraction with low temperature partitioning (LLE-LTP) and paper spray mass spectrometry (PS-MS) was developed to identify and quantify benzodiazepines in beverages. Four types of alcoholic beverages usually consumed in parties and bars were spiked with 5 distinct benzodiazepines (diazepam, alprazolam, bromazepam, clonazepam, and cloxazolam) simulating a drug-facilitated crime occurrence. The direct PS-MS analysis of the spiked beverages revealed a remarkable matrix effect with an unclear detection of protonated benzodiazepines. However, by the application of the LLE-LTP using liquid nitrogen, a prompt and doubtless detection of such compounds was achieved. The quantification potential of the LLE-LTP/PS-MS methodology was demonstrated by using beer as matrix, diazepam as target analyte and cloxazolam as an internal standard. Figures of merit (linearity, limit of detection, linear dynamic range, relative standard deviation, and recovery) were determined and adequate values were obtained. In conclusion, we demonstrated herein that the LLE-LTP/PS-MS methodology has potential to be applied directly at the crime scene through of a portable mass spectrometer and a thermal container for the transport of liquid nitrogen.

Paper spray mass spectrometry applied in the monitoring of a chemical system in dynamic chemical equilibrium: the redox process of methylene blue.

RATIONALE: The monitoring of chemical systems in dynamic equilibrium is not an easy task. This is due to the high rate at which the system returns to equilibrium after being perturbed, which hampers the possibility of following the aftereffects of the disturbance. In this context, it is necessary to use a fast analytical technique that requires no (or minimal) sample preparation, and which is capable of monitoring the species constituting the system in equilibrium. Paper spray ionization mass spectrometry (PS-MS), a recently introduced ambient ionization technique, has such characteristics and hence was chosen for monitoring a model system: the redox process of methylene blue. METHODS: The model system evaluated herein was composed of three cationic species of methylene blue (MB), which coexist in a dynamic redox system: (1) [MB](+) of m/z 284 (cationic MB); (2) [MB + H + e](+•) of m/z 285 (the protonated form of a transient species resulting from the reduction of [MB](+) ); (3) [MB + 2H + 2e](+) or [leuco-MB + H](+) of m/z 286 (the protonated leuco form of MB). Aliquots of a MB solution were collected before and after the addition of a reducing agent (metallic zinc) and directly analyzed by PS-MS for identification of the predominant cationic species at different conditions. RESULTS: The mass spectra revealed that before the addition of the reducing agent the ion of m/z 284 (cationic MB) is the unique species. Upon the addition of the reducing agent and acid, however, the solution continuously undergo discoloration while reduced species derived directly from cationic MB (m/z 285 and 286) are detected in the mass spectra with increasing intensities. Fragmentation patterns obtained for each ionic species, i.e. [MB](+) , [MB + H + e](+•) and [leuco-MB + H](+) , shown to be consistent with the proposed structures. CONCLUSIONS: The PS-MS technique proved to be suitable for an in situ and 'near' real-time analysis of the dynamic equilibrium involving the redox of MB in aqueous medium. The data clearly demonstrated how the redox equilibrium shifts depending on the disturbance caused to the system.

Efficient and versatile fibrous adsorbent based on magnetic amphiphilic composites of chrysotile/carbon nanostructures for the removal of ethynilestradiol.

In this work, chrysotile was used as support to grow carbon nanotubes and nanofibers to produce fibrous amphiphilic magnetic nanostructured composites. Iron impregnated on the chrysotile surface at 1, 5 and 15 wt% was used as catalyst to grow carbon nanostructures by CVD (chemical vapor deposition) with ethanol at 800°C. Raman, TG/DTA, Mössbauer, XRD, BET, SEM, TEM, elemental analyses and contact angle measurements suggested the formation of a complex amphiphilic material containing up to 21% of nanostructured hydrophobic carbon supported on hydrophilic Mg silicate fibers with magnetic Fe cores protected by carbon coating. Adsorption tests for the hormone ethynilestradiol (EE), a hazardous water contaminant, showed remarkable adsorption capacities even compared to high surface area activated carbon and multiwall carbon nanotubes. These results are discussed in terms of the hydrophobic surface of the carbon nanotubes and nanofibers completely exposed and accessible for the adsorption of the EE molecules combined with the hydrophilic Mg silicate surface which allows good dispersion in water. The composites are magnetic and after adsorption the dispersed particles can be removed by a simple magnetic process. Moreover, the fibrous composites can be conformed as threads, screens and pellets to produce different filtering media.

Mikania glomerata Sprengel (Asteraceae) influences the mutagenicity induced by doxorubicin without altering liver lipid peroxidation or antioxidant levels.

As shown in numerous studies, natural compounds may exert adverse effects, mainly when associated with some drugs. The hydroalcoholic extract of Mikania glomerata is the pharmaceutical form present in commercially available syrup used for the treatment of respiratory diseases in popular Brazilian medicine. The objective of the present investigation was (1) to evaluate the preventive effects of standardized hydroalcoholic extract of M. glomerata (MEx) against antitumoral drug doxorubicin (DXR)-induced micronucleated polychromatic erythrocytes (MNPCE) in a subchronic assay in mice, and (2) to determine the liver content of malondialdehyde (MDA) and the antioxidants glutathione (GSH) and vitamin E (VE). Male Swiss mice were treated for 30 d with MEx added to drinking water, combined or not with DXR (90 mg/kg body weight) injected intraperitoneally (ip) 24 h before analysis. The results demonstrated that MEx produced no genotoxic damage, but significantly increased the frequency of MNPCE induced by DXR, indicating a drug-drug interaction. This rise was not accompanied by lipid peroxidation or antioxidants level reduction, as measured by MDA, GSH, and VE. Despite the presence of coumarin (a known antioxidant), MEx may exert adverse effects probably in association with mutagenic compounds, although this effect on DNA damage did not involve oxidative stress.