Litigation in access to universal health coverage for children and adolescents in Brazil.

Background: Brazil's Unified Health System (SUS) ensures universal, equitable, and excellent quality health coverage for all. The broad right to health, supported by the Constitution, has led to excessive litigation in the public sector. This has negatively impacted the financial stability of SUS, created inequality in children and adolescents' access to healthcare, and affected communication between the healthcare system and the judiciary. The enactment of Law Number 13.655 on 25 April 2018, proposed significant changes in judicial decisions. This study aimed to investigate decision-making changes in health litigation involving children and adolescents following the implementation of the new normative model. Methods: The study is cross-sectional, analyzing 3753 national judgment documents from all State Courts of Brazil, available on their respective websites from 2014 to 2020. It compares regional legal decisions before and after the promulgation of Law Number 13.655/2018. Data tabulation, statistical analysis, textual analysis, coding, and counting of significant units in the collected documents were performed. The results of data cross-referencing are presented in tables and diagrams. Results: The majority (96.86%) of legal claims (3635 cases) received partial or total provision of what was prescribed by the physician. The Judiciary predominantly handled these cases individually. The analysis indicates that the decisions made did not adhere to the norms established in 2018. Conclusion: Regional heterogeneity in health litigation was observed, and there was no significant variability in decisions during the studied period, even after the implementation of the new normative paradigm in 2018. Technical-scientific support was undervalued by the magistrates. Prioritizing litigants undermines equity in access to Universal Health Coverage for children and adolescents.

Acid Adaptation Enhances Tolerance of Escherichia coli O157:H7 to High Voltage Atmospheric Cold Plasma in Raw Pineapple Juice.

Pathogens that adapt to environmental stress can develop an increased tolerance to some physical or chemical antimicrobial treatments. The main objective of this study was to determine if acid adaptation increased the tolerance of Escherichia coli O157:H7 to high voltage atmospheric cold plasma (HVACP) in raw pineapple juice. Samples (10 mL) of juice were inoculated with non-acid-adapted (NAA) or acid-adapted (AA) E. coli to obtain a viable count of ~7.00 log10 CFU/mL. The samples were exposed to HVACP (70 kV) for 1-7 min, with inoculated non-HVACP-treated juice serving as a control. Juice samples were analyzed for survivors at 0.1 h and after 24 h of refrigeration (4 °C). Samples analyzed after 24 h exhibited significant decreases in viable NAA cells with sub-lethal injury detected in both NAA and AA survivors (p < 0.05). No NAA survivor in juice exposed to HVACP for 5 or 7 min was detected after 24 h. However, the number of AA survivors was 3.33 and 3.09 log10 CFU/mL in juice treated for 5 and 7 min, respectively (p < 0.05). These results indicate that acid adaptation increases the tolerance of E. coli to HVACP in pineapple juice. The potentially higher tolerance of AA E. coli O157:H7 to HVACP should be considered in developing safe juice processing parameters for this novel non-thermal technology.

Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study.

BACKGROUND: Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU). OBJECTIVE: We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children. METHODS: We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. RESULTS: A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. CONCLUSION: The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.

Discrepancies in Electronic Medical Prescriptions Found in a Hospital Emergency Department: A Prospective Observational Study.

The medication in an electronic prescribing system (EPS) does not always match the patient's actual medication. This prospective study analyzes the discrepancies (any inconsistency) between medication prescribed using an EPS and the medication revised by the clinical pharmacist upon admission to the observation area of the emergency department (ED). Adult patients with multimorbidity and/or polypharmacy were included. The pharmacist used multiple sources to obtain the revised medication list, including patient/carer interviews. A total of 1654 discrepancies were identified among 1131 patients. Of these patients, 64.5% had ≥1 discrepancy. The most common types of discrepancy were differences in posology (43.6%), commission (34.7%), and omission (20.9%). Analgesics (11.1%), psycholeptics (10.0%), and diuretics (8.9%) were the most affected. Furthermore, 52.5% of discrepancies affected medication that was high-alert for patients with chronic illnesses and 42.0% of medication involved withdrawal syndromes. Discrepancies increased with the number of drugs (ρ = 0.44, p < 0.01) and there was a difference between non-polypharmacy patients, polypharmacy ones and those with extreme polypharmacy (p < 0.01). Those aged over 75 years had a higher number of prescribed medications and discrepancies occurred more frequently compared with younger patients. The number of discrepancies was larger in women than in men. The EPS medication record requires verification from additional sources, including patient and/or carer interviews.

Beckwith-Wiedemann syndrome mimicking the classical form of congenital adrenal hyperplasia in newborn screening.

Beckwith-Wiedemann syndrome (BWS) is a common genetic congenital disease characterized by somatic overgrowth and its broad clinical spectrum includes pre- and post-natal macrosomia, macroglossia, visceromegaly, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS occurs due to genetic/epigenetic changes involving growth-regulating genes, located on region 11p15, with an important genotype-phenotype correlation. Congenital adrenal hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases presenting a variety of clinical manifestations due to a deficiency in one of the enzymes involved in cortisol secretion. Early diagnosis based on newborn screening prevents the adrenal crisis and early infant death. However, high 17-hydroxyprogesterone (17-OHP) levels can occur in newborns or premature infants without CAH, in situations of stress due to maternal or neonatal factors. Here, we report new cases of false-positive diagnosis of 21-hydroxylase deficiency during newborn screening - two girls and one boy with BWS. Methylation-specific multiplex ligation-dependent probe amplification revealed a gain of methylation in the H19 differentially methylated region. Notably, all three cases showed a complete normalization of biochemical changes, highlighting the transient nature of these hormonal findings that imitate the classical form of CAH. This report sheds light on a new cause of false-positive 21-hydroxylase deficiency diagnosis during newborn screening: Beckwith-Wiedemann syndrome.

Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells stimulated by cigarette smoke extract.

Smoking causes several diseases such as chronic obstructive pulmonary disease (COPD). Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. Here we evaluated the role of AT-RvD1 (100 nM) in bronchial epithelial cells (BEAS-2B) stimulated by cigarette smoke extract (CSE; 1%; 1 cigarette) for 24 h. CSE induced the productions of IL-1ß, TNF-α, IL-10, IL-4 and IFN-γ as well as the activations of NF-κB and STAT3 and the expression of ALX/FPR2 receptor. AT-RvD1 reduced the IL-1ß and TNF-α production and increased the production of IFN-γ. These effects were reversed BOC2, an antagonist of ALX/FPR2 receptor for AT-RvD1. The production of IL-4 and IL-10 were not altered by AT-RvD1. In addition, AT-RvD1 reduced the phosphorylation of NF-κB and STAT3 when compared to CSE-stimulated BEAS-2B cells. No alteration of ALX/FPR2 expression was observed by AT-RvD1 when compared to CSE group. In the human monocytic leukemia cell line, the relative number of copies of IL-1ß and IL-4 was significantly higher in CSE + AT-RvD1 group compared CSE group, however, the expression of M1 cytokine was more pronounced than M2 profile. AT-RvD1 could be an important target for the reduction of inflammation in the airways associated with smoking.

The influence of exotic and native plants on illnesses with physical and spiritual causes in the semiarid region of Piauí, Northeast of Brazil.

BACKGROUND: Local medical systems (LMS) include native and exotic plants used for the treatment of diseases of physical and spiritual nature. The incorporation of exotic plants into these systems has been the subject of many studies. In this context, an analysis was conducted on the influence of the origin of plants on diseases of physical and spiritual nature in order to evaluate the therapeutic versatility of native and exotic species in these therapeutic targets, to investigate whether exotic plants mainly fill gaps not met by native plants (diversification hypothesis), and identify which species are prioritized in the redundant targets in these two therapeutic groups in the rural community of Morrinhos, Monsenhor Hipólito, Piauí. METHODS: Data collection took place in 2 stages. First, free lists and semi-structured interviews with local residents (n = 134) were conducted to survey plants used for therapeutic purposes and the associated illnesses. Then, another phase of interviews was carried out to evaluate the prioritization between native and exotic plants in redundant therapeutic targets. To test the diversification hypothesis (DH) in each group of illnesses, data were analyzed using generalized linear models (Poisson and Binomial GLMs); versatility was measured by the number of therapeutic indications and compared between resources using the Mann-Whitney test, and prioritization in each group was verified by comparing the proportions of native and exotic plants with the χ2 test. RESULTS: One hundred and thirty-two species of plants were surveyed, being 71 exotic and 61 native, with indications for physical and spiritual illnesses. The results revealed that the diversification hypothesis did not explain the inclusion of exotic plants in the local medical system to treat physical or spiritual illnesses and that the therapeutic versatility of exotic and native resources in the two groups was also similar (p > 0.05). However, exotic plants were prioritized in illnesses with physical causes and native plants in illnesses with spiritual causes. CONCLUSIONS: The local medical system presents similar and distinct patterns in the therapeutic targets, depending on the perspective evaluated. Therefore, it is necessary to investigate the patterns of use of medicinal plants in different sociocultural contexts in order to broaden the debate about the role of plant origin in the selection of treatments for illnesses with different causes.

Prevalence of Antimicrobial Resistance in Escherichia coli and Salmonella Species Isolates from Chickens in Live Bird Markets and Boot Swabs from Layer Farms in Timor-Leste.

The rapid emergence of antimicrobial resistance is a global concern, and high levels of resistance have been detected in chicken populations worldwide. The purpose of this study was to determine the prevalence of antimicrobial resistance in Escherichia coli and Salmonella spp. isolated from healthy chickens in Timor-Leste. Through a cross-sectional study, cloacal swabs and boot swabs were collected from 25 live bird markets and two layer farms respectively. E. coli and Salmonella spp. from these samples were tested for susceptibility to six antimicrobials using a disk diffusion test, and a subset was tested for susceptibility to 27 antimicrobials using broth-based microdilution. E. coli and Salmonella spp. isolates showed the highest resistance towards either tetracycline or ampicillin on the disk diffusion test. E. coli from layer farms (odds ratio:5.2; 95%CI 2.0-13.1) and broilers (odds ratio:18.1; 95%CI 5.3-61.2) were more likely to be multi-drug resistant than those from local chickens. Based on the broth-based microdilution test, resistance to antimicrobials in the Timor-Leste Antimicrobial Guidelines for humans were low, except for resistance to ciprofloxacin in Salmonella spp. (47.1%). Colistin resistance in E. coli was 6.6%. Although this study shows that antimicrobial resistance in chickens was generally low in Timor-Leste, there should be ongoing monitoring in commercial chickens as industry growth might be accompanied with increased antimicrobial use.

The Risk of Reinfection or Primary Hepatitis E Virus Infection at a Liver Transplant Center in Brazil: An Observational Cohort Study.

The hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Seroprevalence in the liver transplantation setting varies according to the seroprevalence of the general population in different countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 10.2% of the recipients and in 9.7% of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.

Sperm morphology of Tingidae Laporte, 1833 (Miroidea: Cimicomorpha).

Here, we describe for the first time the sperm morphology of Tingidae (Heteroptera). They are small insects presenting lacy patterns on their pronotum and hemielytra and are exclusively phytophagous, with many economically important species. We studied five species of the tribe Tingini (Tinginae): Teleonemia scrupulosa, Vatiga illudens, Gargaphia lunulata, Leptopharsa sp., and Corythucha arcuata. Their spermiogenesis process is similar to other Heteroptera, with some differences in the formation of the centriole adjunct. This structure extends in the anteroposterior spermatid axis, flanking the nucleus, possibly contributing to nucleus remodeling and sperm elongation. The mature sperm of Tingidae is also similar to that of other Heteroptera, with features that corroborate the group's monophyly. Our data support previous results for their sister family, Miridae, which exhibits some characteristics exclusive to this taxon, not present in Tingidae or other Heteroptera. They also support the sister relationship of the genera Gargaphia and Leptopharsa and suggest closer relationship between Vatiga and Corythucha. Overall, this study sheds light on the sperm ultrastructure of Tingidae and provides information for understanding the evolution and diversity of Heteroptera. RESEARCH HIGHLIGHTS: The spermiogenesis process and mature sperm are similar to other Heteroptera The centriole adjunct is derived from a strip of a pericentriolar material extending from the centriole Tingidae and Miridae are distinguishable using sperm morphology.

The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases.

BACKGROUND: Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles. METHODS: Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan-Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant. RESULTS: A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%. CONCLUSIONS: This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.

The Impact of Bleomycin Deficit on Survival in Hodgkin's Lymphoma Patients: A Retrospective Study.

PURPOSE: Hodgkin's lymphoma is currently treated with a chemotherapy protocol consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine. Due to Brazil facing a bleomycin shortage in 2017, and this drug's high toxicity, this retrospective study evaluates the effect that the absence of bleomycin had on treatment response and overall survival of Hodgkin's lymphoma patients. METHODS: The medical records of 126 HL patients treated between 2007 and 2021 were reviewed and their data collected, followed by grouping into ABVD and AVD groups according to bleomycin use. Data concerning the patient's characteristics, cancer type, and treatment plan were analyzed with proportion tests, Kaplan-Meier curves. univariate Cox regression, and χ2 tests. RESULTS: No discernible differences were found in this study between the overall survival and recurrence rate of patients treated with bleomycin compared to those without. Additionally, there was an increased risk of death in each subsequent cycle of chemotherapy of the complete ABVD protocol, demonstrating a risk of toxicity. Among the variables analyzed, hypertension and the presence of B symptoms were also associated with an increased risk of death, while the use of radiotherapy significantly improved survival. CONCLUSION: The results of this study suggest that bleomycin did not impact the outcome of Hodgkin's lymphoma treatment. Moreover, the increased risk of death associated with its toxicity during each cycle of treatment raises concerns about its role as an essential component of the gold standard for Hodgkin's lymphoma treatment. Therefore, further research and consideration are needed to reassess the use of bleomycin in Hodgkin's lymphoma treatment protocols.

Beckwith-Wiedemann syndrome mimicking the classical form of congenital adrenal hyperplasia in newborn screening

SUMMARY Beckwith-Wiedemann syndrome (BWS) is a common genetic congenital disease characterized by somatic overgrowth and its broad clinical spectrum includes pre- and post-natal macrosomia, macroglossia, visceromegaly, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS occurs due to genetic/epigenetic changes involving growth-regulating genes, located on region 11p15, with an important genotype-phenotype correlation. Congenital adrenal hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases presenting a variety of clinical manifestations due to a deficiency in one of the enzymes involved in cortisol secretion. Early diagnosis based on newborn screening prevents the adrenal crisis and early infant death. However, high 17-hydroxyprogesterone (17-OHP) levels can occur in newborns or premature infants without CAH, in situations of stress due to maternal or neonatal factors. Here, we report new cases of false-positive diagnosis of 21-hydroxylase deficiency during newborn screening - two girls and one boy with BWS. Methylation-specific multiplex ligation-dependent probe amplification revealed a gain of methylation in the H19 differentially methylated region. Notably, all three cases showed a complete normalization of biochemical changes, highlighting the transient nature of these hormonal findings that imitate the classical form of CAH. This report sheds light on a new cause of false-positive 21-hydroxylase deficiency diagnosis during newborn screening: Beckwith-Wiedemann syndrome.

Práticas de cuidar realizadas por enfermeiros da atenção básica no território: um estudo em Boa Vista, Roraima

Objetivo: Identificar as práticas de cuidar realizadas por enfermeiros da atenção básica no território. Método: Estudo exploratório-descritivo com abordagem qualitativa realizado em dez unidades básicas de saúde situadas na cidade de Boa Vista, Roraima, Brasil. O grupo social foi constituído por oito enfermeiros do quadro efetivo do funcionalismo municipal. A produção dos dados ocorreu durante dezembro de 2022 a fevereiro de 2023 mediada por entrevistas semiestruturadas. Os arquivos em áudio totalizaram aproximadamente uma hora, foram transcritos manualmente e analisados segundo o referencial teórico de Bardin. Resultados: As práticas de cuidar foram organizadas em duas categorias temáticas centrais, a saber: práticas de educação em saúde realizadas por enfermeiros no território e vacinação como prática de cuidar realizada por enfermeiros no território. Conclusão: A educação em saúde foi decodificada como prática de cuidar pelos enfermeiros a partir de ações com grupos prioritários presentes no território orientada por rodas de conversas, palestras educativas e campanhas educacionais sobre infecções sexualmente transmissíveis, saúde mental e uso de drogas. A vacinação foi decodificada a partir da busca ativa de crianças no território, campanhas nas escolas e aplicação de vacinas contra a COVID-19 no território.

Objetivo: Identificar las prácticas asistenciales realizadas por enfermeras de atención primaria en el territorio. Método: Estudio exploratorio-descriptivo con énfasis cualitativo realizado en diez unidades básicas de salud localizadas en la ciudad de Boa Vista, Roraima, Brasil. El grupo social estuvo formado por ocho enfermeras de la administración pública municipal. La producción de datos se realizó entre diciembre de 2022 y febrero de 2023, mediada por entrevistas semiestructuradas. Los archivos de audio totalizaron aproximadamente una hora y veinte minutos, fueron transcritos manualmente y analizados según el marco teórico de Bardin. Resultados: Las prácticas de cuidados se organizaron en dos categorías temáticas centrales, concretamente: prácticas de educación en salud producidos por enfermeras en el territorio y la vacunación como práctica de cuidado realizada por enfermeros en el territorio. Conclusión: La educación en salud fue decodificada como una práctica de cuidado por parte de las enfermeras a partir de acciones con grupos prioritarios presentes en el territorio guiadas por mesas redondas, charlas educativas y campañas educativas sobre infecciones de transmisión sexual, salud mental y consumo de drogas. La vacunación fue decodificada a través de la búsqueda activa de niños en el territorio, campañas en escuelas y la vacunación contra el COVID-19 en el territorio.

Objective: Identify care practices produced by primary care nurses in the territory. Method: Exploratory-descriptive study with a qualitative approach carried out in ten basic health units located in the city of Boa Vista, Roraima, Brazil. The social group was made up of eight nurses from the municipal workforce. Data production took place between December 2022 and February 2023, mediated by semi-structured interviews. The audio files totaled approximately one hour, were transcribed manually and analyzed according to Bardin's theoretical framework. Results: The care practices were organized in two central thematic categories, named: health education practices produced by nurses in the territory and vaccination as a care practice carried out by nurses in the territory. Conclusion: Health education was decoded as a care practice by nurses based on actions with priority groups present in the territory guided by conversation circles, educational lectures and educational campaigns on sexually transmitted infections, mental health and drug use. Vaccination was decoded based on the active search for children in the territory, campaigns in schools and the application of vaccines against COVID-19 in the territory.

Cellular dormancy: A widespread phenomenon that perpetuates infectious diseases.

Under adverse environmental conditions, microorganisms are able to enter a state of cellular dormancy which consists of cell cycle arrest and interruption of multiplication. This process ensures their perpetuation in the infected host organism and enables the spread of disease. Throughout biological evolution, dormancy allowed microorganisms to persist in a harsh niche until favorable conditions for their reactivation were re-established. Here, we propose to discuss the dormancy of bacteria and protozoa pathogens focusing on the potential mechanisms and components associated with dormancy.

Compatibility Assessment of Novel Orodispersible Film Vehicle for Personalized Medicine with Selected Active Pharmaceutical Ingredients.

Orodispersible films (ODFs) are solid pharmaceutical forms for rapid local or systemic release of active ingredients. They are formed by a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity. In this paper, we describe the compatibility and disintegration times of compounded ODFs using OrPhylloTM, a new ready-to-use-vehicle, and APIs from different pharmacological classes, such as 5-hydroxytryptophan (5-HTP) 50 mg, bromopride 5 mg, coenzyme Q10 20 mg, melatonin 3 mg, resveratrol 5 mg, tadalafil 10 mg, vitamin B12 1 mg, or vitamin D3 2000 UI. ODFs were compounded and, subsequently, the samples were assayed using HPLC at initial (t = 0), 7 days (t = 7), 14 days (t = 14), 30 days (t = 30), 60 days (t = 60), 90 days (t = 90), 120 days (t = 120), 150 days (t = 150), and 180 days (t = 180) after compounding. Given the percentage of recovery of the APIs within the films, the beyond-use date of the final products (API + vehicle) was at least 90 days for vitamin D3, 150 days for bromopride and 5-HTP, and 180 days for coenzyme Q10, tadalafil, vitamin B12, resveratrol, and melatonin, when stored at room temperature. The average disintegration time was 46.22 s. This suggests that the OrPhylloTM vehicle is suitable for compounding ODFs with APIs from different pharmacological classes, with good compatibility and fast disintegration.

Shared and distinct neural correlates of first and second language morphological processing in bilingual brain.

While morphology constitutes a crucial component of the human language system, the neural bases of morphological processing in the human brain remains to be elucidated. The current study aims at exploring the extent to which the second language (L2) morphological processing would resemble or differ from that of their first language (L1) in adult Chinese-English bilinguals. Bilingual participants were asked to complete a morphological priming lexical decision task drawing on derivational morphology, which is present for both Chinese and English, when their electrophysiological and optical responses were recorded concurrently. Functional near-infrared spectroscopy (fNIRS) revealed a neural dissociation between morphological and semantic priming effects in the left fronto-temporal network, while L1 Chinese engaged enhanced activation in the left prefrontal cortex for morphological parsing relative to L2 English. In the early stage of lexical processing, cross-language morphological processing manifested a difference in degree, not in kind, as revealed by the early left anterior negativity (ELAN) effect. In addition, L1 and L2 shared both early and late structural parsing processes (P250 and 300 ~ 500 ms negativity, respectively). Therefore, the current results support a unified competition model for bilingual development, where bilinguals would primarily employ L1 neural resources for L2 morphological representation and processing.

Artificial neural networks and adaptive neuro-fuzzy inference systems for prediction of soil respiration in forested areas southern Brazil.

The purpose of this study was to estimate the temporal variability of CO2 emission (FCO2) from O2 influx into the soil (FO2) in a reforested area with native vegetation in the Brazilian Cerrado, as well as to understand the dynamics of soil respiration in this ecosystem. The database is composed of soil respiration data, agroclimatic variables, improved vegetation index (EVI), and soil attributes used to train machine learning algorithms: artificial neural network (ANN) and an adaptive neuro-fuzzy inference system (ANFIS). The predictive performance was evaluated based on the mean absolute error (MEA), root mean square error (RMSE), mean absolute percentage error (MAPE), agreement index (d), confidence coefficient (c), and coefficient of determination (R2). The best estimation results for validation were FCO2 with multilayer perceptron neural network (MLP) (R2 = 0.53, RMSE = 0.967 µmol m-2 s-1) and radial basis function neural network (RBF) (R2 = 0.54, RMSE = 0.884 µmol m-2 s-1) and FO2 with MLP (R2 = 0.45, RMSE = 0.093 mg m-2 s-1) and RBF (R2 = 0.74, 0.079 mg m-2 s-1). Soil temperature and macroporosity are important predictors of FCO2 and FO2. The best combination of variables for training the ANFIS was selected based on trial and error. The results were as follows: FCO2 (R2 = 16) and FO2 (R2 = 29). In all models, FCO2 outperformed FO2. A primary factor analysis was performed, and FCO2 and FO2 correlated best with the weather and soil attributes, respectively.

Genome-wide analysis highlights genetic admixture in exotic germplasm resources of Eucalyptus and unexpected ancestral genomic composition of interspecific hybrids.

Eucalyptus is an economically important genus comprising more than 890 species in different subgenera and sections. Approximately twenty species of subgenus Symphyomyrtus account for 95% of the world's planted eucalypts. Discrimination of closely related eucalypt taxa is challenging, consistent with their recent phylogenetic divergence and occasional hybridization in nature. Admixture, misclassification or mislabeling of Eucalyptus germplasm resources maintained as exotics have been suggested, although no reports are available. Moreover, hybrids with increased productivity and traits complementarity are planted worldwide, but little is known about their actual genomic ancestry. In this study we examined a set of 440 trees of 16 different Eucalyptus species and 44 interspecific hybrids of multi-species origin conserved in germplasm banks in Brazil. We used genome-wide SNP data to evaluate the agreement between the alleged phylogenetic classification of species and provenances as registered in their historical records, and their observed genetic clustering derived from SNP data. Genetic structure analyses correctly assigned each of the 16 species to a different cluster although the PCA positioning of E. longirostrata was inconsistent with its current taxonomy. Admixture was present for closely related species' materials derived from local germplasm banks, indicating unintended hybridization following germplasm introduction. Provenances could be discriminated for some species, indicating that SNP-based discrimination was directly proportional to geographical distance, consistent with an isolation-by-distance model. SNP-based genomic ancestry analysis showed that the majority of the hybrids displayed realized genomic composition deviating from the expected ones based on their pedigree records, consistent with admixture in their parents and pervasive genome-wide directional selection toward the fast-growing E. grandis genome. SNP data in support of tree breeding provide precise germplasm identity verification, and allow breeders to objectively recognize the actual ancestral origin of superior hybrids to more realistically guide the program toward the development of the desired genetic combinations.

Tyrosine kinase inhibitors as an alternative treatment in canine mast cell tumor.

The current gold standard treatment for canine mast cell tumors (MCT) uses vinblastine sulfate (VBL) as chemotherapy, although tyrosine kinase inhibitors (TKI) have recently been shown to be worthy candidates for treatment. This systematic review aimed to analyze the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and complete (CR) or partial response (PR) in dogs with MCT treated with TKI compared to standard VBL treatment. The systematic review was registered in the Open Science Framework (OSF) database under the identifier 10.17605/OSF.IO/WYPN4 (https://osf.io/). An electronic search was performed in nine databases. References from eligible studies were also selected to find more registers. A total of 28 studies met the eligibility criteria, and one more was recovered from the references of eligible studies, totaling 29 selected studies. The overall response rate, complete response, and partial response were higher in dogs treated with tyrosine kinase inhibitors than in dogs treated with vinblastine. The overall survival and progression-free survival of vinblastine-treated dogs were higher compared to tyrosine kinase inhibitors-treated dogs. Dogs with mutated KIT treated with tyrosine kinase inhibitors have longer overall survival and progression-free survival compared to those treated with vinblastine. It is important to consider the limitation of the study which should temper the interpretation of the results, videlicet, the extracted data lacked sample standardization and included variables such as animal characteristics, mutation detection methods, tumor characteristics, and treatment types which may have influenced the outcome of the study. Systematic review registration: https://osf.io/, identifier: 10.17605/OSF.IO/WYPN4.