ABSTRACT Background: Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission induction therapy and approximately two-thirds of treatment-related deaths are due to infectious complications. Methods: From May 2021 to June 2022, children aged one through 18 years, with a recent diagnosis of ALL, admitted to three pediatric oncology centers in Brazil, were enrolled in this multicenter, open-label, randomized, phase 3 clinical trial. Eligible patients were randomly divided into two groups, based on a 1:1 allocation ratio, to receive, or not, levofloxacin as a prophylactic agent during the induction phase. All patients were treated according to the IC-BFM 2009 chemotherapy protocol. Primary endpoints were carbapenemase-producing Enterobacteriaceae (CPE) colonization, Clostridioides difficile diarrhea, and other adverse events related to the use of levofloxacin. The secondary endpoint was febrile neutropenia during induction. The median follow-up was 289 days. Results: Twenty patients were included in this trial, 10 in each group (control and levofloxacin). Mild adverse reactions related to levofloxacin were observed in three patients (30%). Three patients had Clostridioides difficile diarrhea, two in the levofloxacin group and one in the control group (p > 0.99). Only one patient presented colonization by CPE. This patient belonged to the levofloxacin group (p > 0.99). Nine patients presented febrile neutropenia, five in the control group and four in the levofloxacin intervention group (p > 0.99), one patient died due to febrile neutropenia. Conclusion: The use of levofloxacin was shown to be safe in the induction phase in children with de novo ALL. The use of this medication did not increase the rate of colonization by CPE nor the rate of diarrhea by C. difficile. All adverse reactions were mild and remitted either spontaneously or after switching medicine administration from oral to intravenous route.

ABSTRACT Purpose: Nonobstructive azoospermia (NOA) associated with primary spermatogenic failure is a common cause of male infertility usually considered untreatable; however, some reports have suggested that hormonal stimulation to boost the intra-testicular testosterone level and spermatogenesis might increase the chance of achieving pregnancy using homologous sperm. Materials and Methods: We report a series of eight NOA males who received long-term treatment with recombinant human chorionic gonadotropin twice a week for spermatogenesis stimulation. Six males received additional recombinant follicle-stimulating hormone (FSH) supplementation 150-225 IU twice weekly. Results: After recombinant gonadotropin therapy, viable spermatozoa were retrieved from the ejaculate in two patients and by testicular sperm aspiration (TESA) in another two subjects. Singleton spermatozoon retrieved from testes were frozen by vitrification on Cell-Sleeper devices. Two live births were obtained after intracytoplasmic sperm injection with ejaculated spermatozoa and one live birth and an ongoing pregnancy using thawed spermatozoa from TESA. Conclusion: Our proof-of-concept study indicates that hormonal therapy with recombinant gonadotropins could be considered in infertile men with NOA as an alternative to sperm donation. Large-scale studies are needed to substantiate hormone stimulation therapy with recombinant gonadotropins in routine clinical practice for this severe form of male infertility.

ABSTRACT Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP), and (ii) the correlation between DFI and sORP. Materials and Methods: We conducted a prospective study involving 93 infertile males with a history of failed IVF/ICSI. Ten healthy male volunteers served as controls. Semen analysis was carried out according to 2010 WHO manual, whereas seminal sORP was measured using the MiOXSYS platform. SDF was assessed by sperm chromatin structure assay. Participants with DFI >15% underwent a three-month lifestyle intervention program, primarily based on diet and exercise, combined with oral antioxidant therapy using multivitamins, coenzyme Q10, omega-3, and oligo-elements. We assessed changes in semen parameters, DFI, and sORP, and compared DFI results to those of volunteers obtained two weeks apart. Spearman rank correlation tests were computed for sORP and DFI results. Results: Thirty-eight (40.8%) patients had DFI >15%, of whom 31 participated in the intervention program. A significant decrease in median DFI from 25.8% to 18.0% was seen after the intervention (P <0.0001). The mean DFI decrease was 7.2% (95% CI: 4.8-9.5%; P <0.0001), whereas it was 0.42% (95%CI; -4.8 to 5.6%) in volunteers (P <0.00001). No differences were observed in sperm parameters and sORP. Based on paired sORP and DFI data from 86 patients, no correlation was observed between sORP and DFI values (rho=0.03). Conclusion: A 3-month lifestyle intervention program combined with antioxidant therapy reduced DFI in infertile men with elevated SDF and a history of failed IVF/ICSI. A personalized lifestyle and antioxidant intervention could improve fertility of subfertile couples through a reduction in DFI, albeit controlled trials evaluating reproductive outcomes are needed before firm conclusions can be made. Trial registration number and date: clinicaltrials.gov NCT03898752, April 2, 2019.

RESUMO O uso de zeólita na suplementação alimentar pode melhorar a resistência e resiliência aos parasitas gastrintestinal. Os efeitos da suplementação nutricional com zeólita de cordeiros Santa Inês no desempenho, crescimento, infecção por nematoides gastrintestinais e análise econômica foram investigados. Animais fêmeas e machos de 110 dias foram suplementados com quatro níveis de zeólita: 0, 25, 50, e 75 gramas por dia em um delineamento experimental em blocos ao acaso. Os ovos por grama de fezes (OPG), proteína sérica total (PST) e volume globular (VG) foram obtidos de cada animal semanalmente. A cada 14 dias os animais foram pesados e as coproculturas preparadas. Foram abatidos os machos que atingiram peso vivo médio de 34 kg. A análise de viabilidade econômica das dietas foi baseada nos períodos de confinamento de 56 e 91 dias. A zeólita não mitigou significativamente (P > 0,05) a infecção por nematoides, não afetou a PST, o PCV e o desempenho dos cordeiros confinados. A zeólita não foi um suplemento dietético eficiente para evitar a infecção por nematoides gastrintestinais ou melhorar o desempenho dos cordeiros. Os machos abatidos aos 56 dias de confinamento apresentaram maior viabilidade econômica (P < 0,05) comparados àqueles abatidos aos 91 dias. Os machos confinados tiveram desempenho superior (P < 0,05) e melhores resultados econômicos (P < 0,05) comparados às fêmeas. O aumento do período de confinamento reduziu a lucratividade.

ABSTRACT Zeolite as a dietary supplement can improve animal resistance and resilience against gastrointestinal parasites. The effects of different levels of zeolite supplementation on gastrointestinal nematode infection, growth performance, and economic viability of male and female Santa Ines lambs were investigated. Four zeolite levels (0, 25, 50, and 75 g per day) were fed to 110 day-old animals in a randomized block experimental design. Eggs per gram of feces (EPG), total serum protein (TSP), and packed cell volume (PCV) were measured individually every week. The animals were weighed every 14 days and coprocultures were prepared. Male animals that reached an average live weight of 34 kg were harvested. The economic viability analysis of the experimental diets was based on feedlot periods of 56 and 91 days. Dietary supplementation with zeolite did not significantly mitigate infections by nematodes and did not affect TSP, PCV, or feedlot lamb growth performance. Therefore, zeolite was not an effective (P > 0.05) dietary supplement for avoiding gastrointestinal nematode infection or improving growth performance. Male animals slaughtered after 56 days of feeding were more economically viable (P < 0.05) than those slaughtered after 91 days. Feedlotting demonstrated that male animals had superior performance (P < 0.05) and better economic (P < 0.05) results than female animals.

Resumo Galhas são estruturas vegetais neo-formadas que ocorrem em diferentes órgãos. Elas são geradas por uma interação espécie-específica com um organismo indutor. Os indutores manipulam o metabolismo do hospedeiro. Microgramma vacciniifolia (Langsd. & Fisch.) Copel. é uma samambaia epífita neotropical que hospeda duas galhas caulinares, uma induzida por uma espécie de mosquito (Diptera) e outra por uma micromariposa (Lepidoptera). O objetivo deste estudo foi avaliar o impacto desses dois insetos indutores de galhas na bioquímica dos ácidos fenólicos e da cianogênese em galhas, caules e folhas de M. vacciniifolia. Em análise de cromatografia líquida de alta eficiência (CLAE) foi possível indicar a presença de um total de 14 derivados fenólicos, incluindo ácido cafeico e ácido cumárico. Análise das Coordenadas Principais (ACoP) indicou três grupos (1) caules não galhados e galhas induzidas pela micromariposa; (2) galhas induzidas pelo mosquito; (3) galhas induzidas pelo mosquito com parasitoides. Em relação a frequência da cianogênese analisada com o teste do papel picrato, o teste do qui-quadrado apresentou diferença significativa entre as folhas férteis (8,3%), folhas estéreis (27,7%), caules não galhados (0%) e galhas. Entre as galhas, somente aquelas induzidas pelo mosquito foram cianogênicas (15%). Os resultados encontrados indicam, ao menos para as substâncias fenólicas, que os insetos indutores de galha (mosquito e micromariposa) promovem alterações espécie-específica na composição química da samambaia hospedeira.

Abstract Galls, neo-formed plant structures that can occur in different organs, are generated by species-specific interaction with an inducing organism. Inducers manipulate the metabolism of its host. Microgramma vacciniifolia (Langsd. & Fisch.) Copel. is a Neotropical epiphytic fern that hosted two stem galls, one induced by a midge species (Diptera) and other by a micromoth species (Lepidoptera). The aim of this study was to evaluate the impact of these two gall-inducing insects on the biochemistry of phenolic acids and the cyanogenesis in galls, stems and leaves of M. vacciniifolia. High performance liquid chromatography (HPLC) indicated a total of 14 phenol derivatives, including caffeic and coumaric acid. Principal Coordinates Analysis (PCoA) of the phenolic substances indicated three groups consisting (1) non-galled stems and micromoth-induced galls; (2) midge-induced galls; (3) midge-induced galls with parasitoids. Regarding the frequency of cyanogenesis assessed by the picrate paper test, the chi-squared test showed significant difference between fertile leaves (8.3%), sterile leaves (27.7%), non-galled stems (0%) and galls. Among galls, only the midge-induced galls analyzed were cyanogenic (15%). Our results indicated that the different gall-inducers (midge and micromoth) promote species-specific alterations to the phenolic substance composition of the host fern.

Resumen: Bowdichia virgilioides Kunth es una especie arbórea nativa del bosque Cerrado brasileño que ha sido considerada en peligro de extinción debido a su sobreexplotación en las últimas décadas. Dada su lenta y difícil propagación en ambientes naturales, la propagación de plantas en viveros aparece como una estrategia interesante para preservar esta especie en peligro de extinción. Por lo tanto, en este estudio empleamos un amplio rango de temperaturas (es decir, desde -25 °C a -196 °C) para almacenar semillas de B. virgilioides en un corto plazo y evaluar su eficiencia a través de la tasa de germinación de semillas, el índice de velocidad, el tiempo y la sincronía, así como el crecimiento y la calidad de las plántulas. El porcentaje de germinación se vio afectado ligeramente por el tiempo de almacenamiento (de hasta 32 semanas) a una temperatura de 25 °C. A pesar de eso, después de 32 semanas de almacenamiento, todas las temperaturas de almacenamiento dieron como resultado la germinación de las semillas, con crecimiento y calidad de plántulas similares. En general, nuestros resultados destacan que las semillas de esta especie se pueden almacenar en un corto plazo en una amplia gama de temperaturas, facilitando así la propagación a gran escala en viveros.

Abstract: Bowdichia virgilioides Kunth is a tree species native to the Brazilian Cerrado that has been listed as an endangered species due to its overexploitation in the last decades. Given its slow and difficult propagation in natural environments, propagation in plant nurseries appears as an interesting strategy to preserve this endangered species. Therefore, in this study we employed a wide range of temperatures (i.e. from -25°C to -196°C) to store seeds of B. virgilioides in the short-term, and evaluated its efficiency by assessing seed germination rate, speed index, time and synchrony, as well as seedling growth and quality. Germination percentage was only slightly negatively affected by storage time (up to 32 weeks) at 25°C. Despite that, after 32 weeks of storage, all storage temperatures resulted in similar seed germination parameters and seedling growth and quality. Overall, our results highlight that the seeds of this species can be stored in the short-term at a wide range of temperatures, facilitating large-scale propagation in plant nurseries.

Resumo: Bowdichia virgilioides Kunth é uma espécie arbórea nativa do Cerrado brasileiro que tem sido considerada ameaçada de extinção devido à sua superexploração nas últimas décadas. Por ter uma propagação lenta e dificultada em ambientes naturais, a propagação em viveiros de plantas surge como uma estratégia interessante para preservar esta espécie ameaçada de extinção. Portanto, neste estudo, empregamos uma ampla gama de temperaturas (i.e., de -25°C a -196°C) para armazenar sementes de B. virgilioides em curto prazo e avaliamos sua eficiência através da taxa de germinação de sementes, índice de velocidade, tempo e sincronia, bem como crescimento e qualidade da plântula. A porcentagem de germinação sofreu pequenas reduções com o tempo de armazenamento (de até 32 semanas) apenas na temperatura de 25°C. Apesar disso, após 32 semanas de armazenamento, todas as temperaturas de armazenamento resultaram em parâmetros de germinação de sementes, crescimento e qualidade de plântulas semelhantes. De forma geral, nossos resultados demonstram que as sementes dessa espécie podem ser armazenadas no curto prazo em uma ampla faixa de temperatura, facilitando a propagação da espécie em larga escala em viveiros.

Resumo As substancias anabólicas tem sido cada vez mais utilizadas por fisiculturistas e atletas com o objetivo de melhorar o desempenho e a estética. No entanto, essa prática tem causado algumas preocupações aos médicos e pesquisadores, devido ao desconhecimento das consequencias que o uso indiscriminado e ilícito dessas substâncias podem causar. Diante disso, este estudo analisou os efeitos de dois esteroides anabolizantes (EA) comercialmente disponíveis, Winstrol Depot® (Stanozolol) e Deposteron® (cipionato de testosterona), na densidade neuronal das regiões corticais límbica, motora e sensitive bem como das áreas CA1, CA2, CA3 do hipocampo. Foram utilizados 60 camundongos Swiss (30 machos e 30 fêmeas), separados em três grupos: controle e dois grupos experimentais, que receberam o EA. De cada cérebro, foram coletadas amostras homotípicas e semi-seriadas em cortes frontais das áreas estabelecidas para o estudo. Os resultados mostraram que as fêmeas tratadas com cipionato de testosterona apresentaram uma redução em todas as regiões analisadas já as fêmeas tratadas com Stanozolol mostraram uma diminuição em algumas áreas do hipocampo. Em relação aos animais machos, o stanozolol levou a uma diminuição na densidade neuronal em uma região do hipocampo. Estes dados nos permitem concluir que doses supra fisiológicas de esteroides utilizadas neste estudo podem causar danos consideráveis ao tecido nervoso com comprometimento ultraestrutural e consequentemente comportamental. Essas alterações podem interferir na perda de rendimento físico e no desempenho de atletas e não atletas e podem causar danos irreparáveis a indivíduos que fazem uso irresponsável destes EA.

Abstract Anabolic substances have been increasingly used by bodybuilders and athletes with the goal of improving performance and aesthetics. However, this practice has caused some concern to physicians and researchers because of unknowledge of consequences that the indiscriminate and illicit use of these substances can cause. Thus, this study analyzed the effects of two commercially available anabolic steroids (AS), Winstrol Depot® (Stanozolol) and Deposteron® (Testosterone Cypionate), in the neuronal density of limbic, motor and sensory regions on the cerebral cortex and in CA1, CA2, CA3 regions of the hippocampus. A total of 60 Swiss mice were used (30 males and 30 females), separated into three groups: control and two experimental groups, which received the AAS. From each brain, homotypic and semi-serial samples were taken in frontal sections from areas established for the study. The results showed that females treated with testosterone cypionate presented a reduction in all regions tested and the ones treated with Stanozolol showed a decrease in some hippocampal areas. Regarding male animals, stanozolol led to a decrease in neuron number in one hippocampal region. These data allow us to conclude that supra-physiological doses of steroids used in this study, can cause considerable damage to nervous tissue with ultrastructural and consequently behavioral impairment. These changes could interfere with the loss of physical yield and performance of athletes and non-athletes and may cause irreparable damage to individuals making irresponsible use of anabolic steroids.

This work presents some modifications in the post-synthetic processing for a classical arsenic reagent: AsI3. In comparison with the widely used analog, the trichloride, arsenic triiodide presents several advantages such as low toxicity, air stability, and low volatility. It was used as a synthetic precursor in the preparation of a variety of arsenic(III) derivatives like arsines, arsenites, and thioarsenites. Besides that, AsI3 was submitted to a diversity-oriented Grignard reaction in the preparation of a homologous series of trialkyl arsines ranging from AsC3H9 to AsC12H27. The series was analyzed by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to provide a trialkyl arsines library that can be used for the direct analysis of natural samples.