Effects of the insecticide flupyradifurone on Anticarsia gemmatalis caterpillar and its predator Podisus nigrispinus.

The caterpillar Anticarsia gemmatalis (Lepidoptera: Noctuidae) is a prevalent pest in soybean plantations, managed using both natural and synthetic chemical products. However, the emergence of resistance in some populations emphasizes the need to explore alternative insecticides. Flupyradifurone, a neurotoxic insecticide, has not been previously used for controlling A. gemmatalis. This study evaluated the potential of flupyradifurone in the management of A. gemmatalis. Initially, the toxicity and anti-feeding effects, as well as histopathological and cytotoxic impacts, of flupyradifurone on A. gemmatalis were evaluated. Subsequently, the indirect effects of flupyradifurone on the midgut and fat body of the predator Podisus nigrispinus (Hemiptera: Pentatomidae) were verified. The results indicate the susceptibility of caterpillars to flupyradifurone, with an LC50 of 5.10 g L-1. Furthermore, the insecticide adversely affects survival, induces an anti-feeding response, and inflicts damage on the midgut of the caterpillars. However, flupyradifurone also leads to side effects in the predator P. nigrispinus through indirect intoxication of the caterpillars, including midgut and fat body damage. While flupyradifurone demonstrates toxicity to A. gemmatalis, suggesting its potential for the chemical control of this pest, the indirect negative effects on the predator indicate the need for its controlled use in integrated pest management programs with the insecticide and the predator.

Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

BACKGROUND: Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. METHODS: We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. RESULTS: A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). CONCLUSION: Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Correction: Pontes do Nascimento et al. Synthesis of Mesoporous Zn1-xMxAl2O4 Substituted by Co2+ and Ni2+ Ions and Application in the Photodegradation of Rhodamine B. Materials 2020, 13, 2150.

In the original publication [...].

Prognosis of programmed ventricular stimulation in adult patients with syncope of unexplained origin: A historical cohort.

Background: Programmed ventricular stimulation (PVS) during electrophysiological study (EPS), is a globally accepted tool for risk stratification of sudden cardiac death (SCD) in some specific clinical situations. The aim of this study was to evaluate the prognosis of ventricular arrhythmia induction in a cohort of patients with syncope of undetermined origin (SUO). Methods: This is a historical cohort study in a population of patients with SUO referred for EPS between the years 2008-2021. In this interval, 575 patients underwent the procedure. Results: Patients with induced ventricular arrhythmias had a higher occurrence of structural heart disease (36.7% vs. 76.5%), ischemic heart disease (28.2 vs. 57.1%), heart failure (15.5% vs. 34.4%), and lower left ventricular ejection fraction (59.16% vs. 47.51%), when compared to the outcome with a negative study. PVS triggered ventricular arrhythmias in 98 patients, 62 monomorphic and 36 polymorphic. During a median follow-up of 37.6 months, 100 deaths occurred. Only the induction of sustained ventricular arrhythmias showed a significant association with the primary outcome (all-cause mortality) with a p value <.001. After the performance of EPS, 142 patients underwent cardioverter-defibrillator (ICD) implantation. At study follow-up, 30 patients had therapies by the device. Only the induction of sustained monomorphic ventricular arrhythmia showed statistically significant association with appropriate therapies by the device (p = .012). Conclusion: In patients with SUO, the induction of sustained monomorphic ventricular arrhythmia after programmed ventricular pacing is related to a worse prognosis, with a higher incidence of mortality and appropriate therapies by the ICD.

Prevalence and antimicrobial resistance profile of pathogens isolated from patients with urine tract infections admitted to a university hospital in a medium-sized Brazilian city.

This study aimed to determine the antibiotic profile of microorganisms isolated from urine samples of patients with community urine tract infections (UTI) admitted to the University Hospital of the Federal University of Sao Carlos to support an appropriate local empirical treatment. A retrospective cross-sectional study was conducted from October 2018 to October 2020. Data from 1,528 positive urine cultures for bacterial pathogens and antibiograms were tabulated. Bacterial species prevalence and their resistance profile were analyzed and compared by sex and age. For Gram-negative fermenting bacteria, resistance rates were compared between patients with previous hospitalization and the total of infections caused by this group. For comparisons, the Chi-square test was performed, using Fisher's exact test when necessary (BioEstat program, adopting p ≤ 0.05). A multivariate analysis was applied to assess the effect of the studied variables in predicting multidrug resistance. Infections were more prevalent in women and older adults. Gram-negative bacteria represented 90.44% of total cultures. In both sexes, E. coli prevalence was significantly higher in adults compared with older adults (p < 0.0001). For several antibiotics, resistance rates were higher in the older adults compared with other ages and in patients with Gram-negative fermenting infections and previous hospitalization compared with the total of infections by this group of bacteria. The closer to the hospitalization, the higher the number of antibiotics with superior resistance rates. Resistance rates for aminoglycosides, carbapenems, ceftazidime, nitrofurantoin, piperacillin+tazobactam, and fosfomycin were less than 20%, considered adequate for empirical treatment. Only hospitalization in the previous 90 days was statistically significant in predicting infections by multidrug-resistant bacteria.

Prevalence and antimicrobial resistance profile of pathogens isolated from patients with urine tract infections admitted to a university hospital in a medium-sized Brazilian city

ABSTRACT This study aimed to determine the antibiotic profile of microorganisms isolated from urine samples of patients with community urine tract infections (UTI) admitted to the University Hospital of the Federal University of Sao Carlos to support an appropriate local empirical treatment. A retrospective cross-sectional study was conducted from October 2018 to October 2020. Data from 1,528 positive urine cultures for bacterial pathogens and antibiograms were tabulated. Bacterial species prevalence and their resistance profile were analyzed and compared by sex and age. For Gram-negative fermenting bacteria, resistance rates were compared between patients with previous hospitalization and the total of infections caused by this group. For comparisons, the Chi-square test was performed, using Fisher's exact test when necessary (BioEstat program, adopting p ≤ 0.05). A multivariate analysis was applied to assess the effect of the studied variables in predicting multidrug resistance. Infections were more prevalent in women and older adults. Gram-negative bacteria represented 90.44% of total cultures. In both sexes, E. coli prevalence was significantly higher in adults compared with older adults (p < 0.0001). For several antibiotics, resistance rates were higher in the older adults compared with other ages and in patients with Gram-negative fermenting infections and previous hospitalization compared with the total of infections by this group of bacteria. The closer to the hospitalization, the higher the number of antibiotics with superior resistance rates. Resistance rates for aminoglycosides, carbapenems, ceftazidime, nitrofurantoin, piperacillin+tazobactam, and fosfomycin were less than 20%, considered adequate for empirical treatment. Only hospitalization in the previous 90 days was statistically significant in predicting infections by multidrug-resistant bacteria.

Water-soluble Moringa oleifera Seed Lectin Exhibits Monoaminergic Pathway-linked Anti-depressive-like Effects in Mice.

OBJECTIVES: The present study investigated the anti-depressive-like (anti-immobility) effect of a lectin from Moringa oleifera seeds (WSMoL) in mice. METHODS: To evaluate an acute effect, the animals were treated with WSMoL (1, 2, and 4 mg/kg, i.p.) 30 min before the tail suspension test (TST). To investigate the involvement of monoaminergic and nitrergic signaling, the mice were pre-treated with selective antagonists. The role of the WSMoL carbohydrate-recognizing domain (CRD) was verified using previous blockage with casein (0.5 mg/mL). The subacute anti-immobility effect was also evaluated by administering WSMoL (1, 2, and 4 mg/kg, i.p.) once a day for 7 d. Finally, an open field test (OFT) was performed to identify possible interferences of WSMoL on animal locomotory behavior. RESULTS: WSMoL reduced the immobility time of mice in the TST at all doses, and combined treatment with fluoxetine (5 mg/kg, i.p.) and WSMoL (1 mg/kg) was also effective. The CRD appeared to be involved in the anti-immobility effect since the solution of WSMoL (4 mg/kg) pre-incubated with casein showed no activity. The lectin effect was prevented by the pre-treatment of mice with ketanserin, yohimbine, and SCH 23390, thereby demonstrating the involvement of monoaminergic pathways. In contrast, pre-treatment with L-NAME, aminoguanidine, and L-arginine did not interfere with lectin action. WSMoL exhibited a subacute effect in the TST, thereby reducing immobility time and increasing agitation time even on the seventh day. OFT data revealed that the anti-immobility effect was not caused by interference with locomotor behavior. CONCLUSION: WSMoL elicits an anti-depressant-like effect that is dependent on monoaminergic signaling.

A rare case of skin metastasis from a chordoma.

Chordoma is an uncommon, indolent malignant tumor arising from notochordal remnants. The incidence of distant metastasis varies between 30 and 40% in different series. Even though local involvement of the skin by direct invasion of chordoma is common, distant skin metastasis are rare, with less than 30 cases reported in the literature. The present clinical case illustrates the slow-growing natural history of a sacral chordoma, which evolved with lung metastasis, followed three years later by skin metastasis, thus giving us the opportunity to review the diagnostic approach, as well as the clinical and histopathological characteristics of this rare tumor.

Weathering impacts on petroleum biomarker, aromatic, and polar compounds in the spilled oil at the northeast coast of Brazil over time.

After the wide oil spill reached the northeast of Brazil, the resurgence of oil was recorded and to evaluate this oil in detail, two samples collected in the state of Pernambuco in 2019 and 2021 were submitted to multiple analytical techniques. For both, we have found similar saturated biomarkers and triaromatic steroid ratios, implying that they are from the same spilled source. The n-alkanes, isoprenoids, and cycloalkanes were almost completely degraded due to evaporation, photooxidation, and/or biodegradation processes. The preferential loss of less alkylated PAHs than the more alkylated ones suggests that biodegradation was the most active process. This hypothesis is reinforced by the formation of mono and dicarboxylic acids assessed by GC × GC-TOFMS and ESI(-) FT-ICR MS high-resolution techniques. Furthermore, based on the ESI(-) FT-ICR MS results, three new ratios were proposed to evaluate the progress of the biodegradation process over time: Ox>2/O, SOx/SO, and SOx/N.

Avaliação da procalcitonina como tecnologia de saúde a ser incorporada em um hospital universitário para redução de tempo de tratamento com antimicrobianos / Evaluation of procalcitonin as a health technology to be incorporated in a university hospital to reduce treatment time with antimicrobials

Introdução: O uso do biomarcador procalcitonina (PCT) de forma racionalizada pode contribuir para reduzir o uso excessivo de antimicrobianos, poupar recursos e qualificar o cuidado com o paciente. Objetivo: Avaliar a eficácia da PCT na redução do tempo de tratamento com antimicrobianos e o impacto financeiro e factibilidade da incorporação desta tecnologia a partir de cenários simulados em um hospital de pequeno porte e média complexidade. Material e Métodos: Revisão da literatura, a partir da base de dados Pubmed seguida de análise de custo em quatro cenários simulados, comparando o PCR com a PCT. Foram incluídos ensaios clínicos randomizados e revisões sistemáticas cuja intervenção consistia no uso de PCT para guiar o tempo de tratamento com antimicrobianos. A seleção e extração dos dados foi realizada por quatro revisores independentes. A análise de custo foi realizada por meio de cenários simulados com os antimicrobianos de maior impacto na instituição totalizando doze terapias analisadas, a partir de dados de custos efetivamente desembolsados. Resultados: Foram selecionados 8 artigos para a análise final. A PCT possibilitou redução significativa de tempo de tratamento, redução de mortalidade, tempo de internação, eventos adversos e custos. A simulação de custo demonstrou que o cenário com PCT foi mais econômico para 67% das terapias analisadas, chegando à uma economia de até R$567,86 por tratamento, no caso da terapia combinada com meropenem, vancomicina e polimixina. Conclusão: A terapia guiada pela PCT reduz tempo de tratamento, internação e mortalidade apresentando impacto considerável na redução dos custos diretos, sendo factível a sua incorporação no cenário analisado

Introduction: The use of the procalcitonin (PCT) biomarker in a rationalized manner can contribute to reducing the excessive usage of antimicrobial, saving resources and improving patient care. Objective: To evaluate the effectiveness of PCT in reducing antimicrobial treatment time and the financial impact and feasibility of incorporating this technology based on simulated scenarios in a small and medium-complexity hospital. Material and Methods: Literature review, based on the Pubmed database followed by cost analysis in four simulated scenarios, comparing PCR with PCT test. Randomized clinical trials and systematic reviews whose intervention consisted of the use of PCT to guide the duration of antimicrobial treatment were included. Data selection and extraction was carried out by four independent reviewers. The cost analysis was carried out through simulated scenarios with the twelve therapies with the greatest impact on the institution, based on data of costs actually disbursed. Results: The final analysis included 8 articles. PCT resulted in significant reduction of duration of antibiotic treatment, reduction in mortality, length of stay, adverse events and costs. The cost simulation demonstrated that the PCT scenario was more economical for 67% of therapies analyzed, reaching savings up to R$567.86 per treatment, in the case of combined therapy with meropenem, vancomycin and polymyxin.Conclusion: PCT-guided therapy reduces treatment duration, hospitalization and mortality, presenting a considerable impact on reducing direct costs, making it feasible to incorporate it into the analyzed scenario.

The lectin from Schinus terebinthifolia leaf (SteLL) reduces immobility of mice on the tail suspension test dependent on the monoaminergic and nitric oxide signaling.

Depression underlies a common psychiatric disorder that has been rising in the diagnosis of long-term disabilities worldwide. Natural products have been studied as an antidepressant and anxiolytic agents aiming to make available new options for the daily basis treatment of those psychological disorders. SteLL is a lectin extracted from Schinus terebinthifolia leaf that has been revealed as an antimicrobial, immunomodulatory, antitumor, and antinociceptive agent. Nonetheless, the efficacy of SteLL in the treatment of depression has not yet been explored. In view of this, the aim of this study was to investigate the effect of SteLL in an acute protocol for symptoms of depression using the tail suspension test (TST) to assess despair. Administration of SteLL (1, 2 e 4 mg/kg) significantly diminished the immobility time of animals in the TST and this anti-immobility action was dependent on the carbohydrate-recognizing domain (CRD) since the prior incubation with casein (an inhibitor of SteLL carbohydrate-binding property) blocked the effect. SteLL effect was also reversed by pre-treatment with pharmacological antagonists of α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and D1 dopamine receptor as well as by a selective inhibitor of iNOS (aminoguanidine). l-arginine, a precursor of NO, potentiated SteLL anti-immobility effect. In a subacute evaluation, the anti-immobility effect of SteLL persisted after seven days of treatment. Our findings suggest a role of SteLL in the modulation of depression mostly through monoaminergic and nitric oxide signaling.

População indígena em tempos de pandemia: reflexões sobre saúde a partir da perspectiva decolonial / Indigenous population in pandemic times: reflections about health in a decolonial perspective

Resumo A pandemia do novo coronavírus suscita discussões sobre saúde relacionadas à proteção da vida por meio de medidas preventivas e de contenção da covid-19, sob orientação da Organização Mundial da Saúde. No Brasil, o debate perpassa os marcadores de classe, raça, gênero e etnia, expondo as vulnerabilidades a que determinados povos são submetidos historicamente, para além da ação do vírus Sars-CoV-2. Este artigo apresenta uma pesquisa documental de cunho qualitativo, acerca dos sentidos produzidos sobre a saúde da população indígena diante da pandemia da covid-19, com enfoque nas notícias publicadas no site da Articulação dos Povos Indígenas do Brasil, entre março e setembro de 2020. As 65 notícias foram organizadas em três eixos: Ações do Governo e órgãos oficiais; Questão territorial; e Organização política e resistência indígena, e analisadas com base no referencial teórico dos estudos decoloniais. Os resultados apontaram para um aumento das violações de direito dos povos originários por parte da gestão atual do governo federal, através do acirramento das crises ambientais, da morosidade e ausência de políticas públicas emergenciais contra a covid-19, evidenciando, também, a resistência destes povos, por meio de uma luta ancestral que valoriza os saberes e práticas tradicionais no cuidado em saúde.

Abstract The pandemic of the new coronavirus enables discussions about health related to protecting life by adopting covid-19 prevention and contention measures, based on the World's Health Organization guidance. In Brazil, the debate involves issues of class, race, gender, and ethnicity, exposing vulnerabilities to which certain peoples are historically submitted beyond the action of the Sars-CoV-2 virus. This article presents qualitative documental research about the meanings produced regarding the health of indigenous peoples in face of the covid-19 pandemic focusing on news reports published in the site of the Articulação dos Povos Indígenas do Brasil between March and September of 2020. The 65 publications were organized in three categories: Actions from official departments and government; Territorial issue; and Political organization and indigenous resistance, and analyzed based in theories of decolonial studies. The results point to an increase of violations of the indigenous peoples' rights by the current executive office of the federal government, by aggravating environmental crisis, the morosity and absence of emergency public policies against covid-19, also evidencing the resistance of these peoples by an ancient struggle that values knowledge and traditional healthcare practices.

Mudanças curriculares no ensino da Saúde Coletiva na graduação de fonoaudiólogos: análise de um curso da região nordeste / Public health curricular changes in speech-language-hearing therapist training: Analysis of an undergraduate program in Northeastern Brazil / Cambios curriculares em la enseñanza de la Salud Pública en la graduación de fonoaudiología: análisis de un curso de la región nordeste

Introdução: Compreender o modo como o ensino da Saúde Coletiva (SC) tem sido inserido nos currículos da fonoaudiologia é fundamental para o entendimento dos desafios da formação de profissionais para o Sistema Único de Saúde (SUS). Objetivo: Analisar as mudanças curriculares no ensino da SC ocorridas em um curso de Fonoaudiologia na região nordeste, desde sua criação ao momento atual. Método: A coleta dos dados compreendeu a análise documental dos Projetos Políticos Pedagógicos, planos de estágio e planos de ensino do Curso de graduação em Fonoaudiologia, desde sua criação até o momento atual. Resultados: Os resultados referem que houve mudanças, mesmo que mínimas, na inserção do ensino da SC na fonoaudiologia no curso estudado com o decorrer dos anos. A principal delas foi a ampliação dos componentes curriculares que abordavam o Campo da SC, que avançaram deum componente isolado na metade do curso, para um eixo horizontal, composto de componentes que vão do primeiro ao último ano do curso. Conclusão: Apesar das lacunas foi possível observar o caminho que a graduação em fonoaudiologia tem seguido, abandonando aos poucos o modelo hospital cêntrico e se aproximando da integralidade prezada pelo SUS e do que é preconizado pelas Diretrizes Curriculares de Fonoaudiologia.

Introduction: It is essential to understand how public health teaching has been included in speech-language-hearing curricula to address the challenges of training professionals for the Unified Health System.Objective: To analyze cu rricular changes in public health teaching in a speech-language-hearing undergraduate program in Northeastern Brazil from its creation to the present. Method: Data were collected with documentary analysis of pedagogical frameworks, internship plans, and lesson plans in a speech-language-hearing program from its creation to the present. Results: The results demonstrate that changes, though slight ones, have taken place over the years in the public health teaching in the speech-language-hearing program approached in this study. The main change was the increase in public health curricular components, advancing from one component alone halfway through the program to a horizontal approach with components offered from the first to the last year of the program. Conclusion: Despite the gaps, the speech-language-hearing undergraduate program is progressively shifting from a hospital-centered model toward the comprehensive approach valued by the Unified Health System and expected in the Speech-Language-Hearing Curricular Guidelines.

Introducción: Comprender cómo se ha insertado la enseñanza de la Salud Pública (SP) en los planes de estudio de logopedia es fundamental para comprender los desafíos de la formación de profesionales para el Sistema Único de Salud (SUS). Objetivo: Analizar los cambios curriculares en la educación de la SP que se han producido en un curso de Patología del Habla y Lenguaje en la noreste región, desde su creación hasta el momento actual. Método: La recolección de datos comprendió análisis documental de Proyectos Políticos Pedagógicos, planes de pasantía y planes de enseñanza de la Carrera de Licenciatura en Patología del Habla y Lenguaje, desde su creación hasta la actualidad. Resultados:Los resultados indican que hubo cambios, aunque mínimos, en la inserción de la enseñanza de SP en logopedia en el curso estudiado a lo largo de los años. El principal fue la ampliación de los componentes curriculares que abordaban el Campo de la SP, que pasó de un componente aislado en la mitad del curso, a un eje horizontal, compuesto por componentes que van desde el primer hasta el último año del curso. Conclusión: A pesar de las brechas, se pudo observar el camino que ha seguido la graduación en logopedia, abandonando paulatinamente el modelo hospitalario y acercándose a la integralidad valorada por el SUS y lo recomendado por las Directrices Curriculares Nacionales de Fonoaudiología.

The Anxiolytic Activity of Schinus terebinthifolia Leaf Lectin (SteLL) Is Dependent on Monoaminergic Signaling although Independent of the Carbohydrate-Binding Domain of the Lectin.

The potential of plant lectins (carbohydrate-binding proteins) for the treatment of neurological disorders such as anxiety and depression has started to be reported in the last few years. Schinus terebinthifolia leaves contain a lectin called SteLL, which has displayed antimicrobial, immunomodulatory, antitumor, and analgesic activities. However, the effects of SteLL on the Central Nervous System (CNS) have not yet been determined. In this study, we investigated the in vivo anxiolytic effect of SteLL in mice using the open field (OF) and elevated plus maze (EPM) tests. In the OF, SteLL (1, 2, and 4 mg/kg, i.p.) did not interfere with the number of crossings but significantly reduced the number of rearings. In the EPM, SteLL 4 mg/kg and the combination SteLL (1 mg/kg) plus diazepam (1 mg/kg) significantly increased the time spent in the open arms while reducing the time spent in the closed arms. The anxiolytic effect of SteLL did not seem to be dependent on the carbohydrate-binding domain of the lectin. Nevertheless, the SteLL effect in the EPM was reversed by the pretreatment with the pharmacological antagonists of the α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and the D1 dopamine receptor. Overall, our results suggest that the anxiolytic effect of SteLL is dependent on the monoaminergic signaling cascade.

Gastric Cancer With Multiple Bone Metastases: An Uncommon Primary Presentation.

Gastric cancer (GC) is a worldwide health condition of major concern, with gastric carcinoma with signet ring cell features being increasingly reported. A 61-year-old woman was admitted to the Emergency department with back pain, gastrointestinal complaints, and weight loss. A lumbar and hip computed tomography (CT) was performed and revealed multiple suspicious secondary bone lesions. Laboratory test results reported anemia, thrombocytopenia, and elevated alkaline phosphatase. On thoracic-abdominal-pelvic CT, multiple bone lesions suggestive of metastases were visible on the vertebral spine, ribs, pelvic bones, and proximal femurs, but no identifiable primary or visceral lesions were described. Upper endoscopy identified a gastric adenocarcinoma, and both gastric and bone lesions, especially bone lesions, contained a relevant amount of signet ring cells. The patient was referred to the Medical Oncology department, however, her condition evolved unfavorably. GC with restricted bone metastasis is rare at presentation and has a poor prognosis. Despite its infrequency, clinicians should consider GC involvement when evaluating secondary suspicious bone lesions.

A Case of Varicella-Zoster Virus Meningomyelitis in an HIV-1-Infected Patient: Facing the Challenges Related to Its Management and Prognosis.

Varicella-zoster virus (VZV) myelitis is a rare complication of herpes zoster. Diagnosing and treating this entity may be challenging. Clinical outcomes vary and neurological sequelae may be seen despite treatment. We report a case of a 43-year-old woman with human immunodeficiency virus type 1 (HIV-1) infection (CD4 cell count 191 cells/µL - 14%; undetectable viral load) who was started on antiretroviral treatment eight months before. She presented with VZV meningitis and transverse myelitis and concomitant thoracic vesicular rash at the dermatomal level T6. Neurological examination revealed neck stiffness, paraplegia, sensory level below T4, and autonomic dysfunction. Magnetic resonance imaging (MRI) revealed signs of myelitis from C4 to T10 and VZV DNA by polymerase chain reaction (PCR) was positive (20,00,000 cp/mL) in the cerebrospinal fluid (CSF). The patient completed four weeks of intravenous acyclovir and systemic corticosteroids. Repeat lumbar puncture returned negative for VZV PCR and MRI showed spinal cord improvement. However, only partial neurological improvement was observed after six months. Some features of the present case may be associated with an unfavorable outcome, including high VZV viral load in the CSF and rapid progression of neurological deficits to paraplegia and sphincter dysfunction. Moreover, the recovery of CD4+ cells from 4% to 14% after starting antiretroviral treatment might also have contributed to the extension of myelopathy. Further studies are needed to improve the understanding of VZV myelitis course and optimize its treatment.

Effects of 5-ALA mediated photodynamic therapy in oral cancer stem cells.

The aim of the present study was to investigate the effects of PDT using the photosensitizer 5-aminoulevulinic acid (5-ALA) in oral squamous cell carcinoma (OSCC) behavior, mainly regarding its role on the cancer stem cell (CSC) phenotypes and in maintenance of the stem cell properties. Two OSCC cell lines were used and divided in the groups: Control, 5-ALA, LED 6 J/cm2 and PDT. MTT and Neutral red assays were used to access cellular viability, cell migration was evaluated by the wound healing assay. The stem cell phenotype was analyzed by flow cytometry to evaluate the CD44high/ESAhigh, CD44high/ESAlow and CD44low populations, by the clonogenic and tumor sphere formation assays as well as by RT-qPCR. The presence of Protoporphyrin IX in each CSC fraction was evaluated by flow cytometry. The OSCC cell lines showed a significant decrease in cell viability and migration after PDT. The percentage of CD44high/ESAhigh cells decreased after PDT, which was associated with an increase in the CD44low cells and with a functional decrease in the colony and sphere formation capacity. CD44high/ESAhigh cells showed increased PpIX, which contributed for their greater sensitivity to PDT. INV gene increased significantly after PDT, indicating cellular differentiation. Altogether, our results demonstrate that 5-ALA mediated PDT decreases not only the fraction of oral CSC but also their functional capabilities, inducing their differentiation.

Antibody response to a new member of the DBL family (EBP2) after a brief Plasmodium vivax exposure.

Plasmodium vivax blood-stage invasion into reticulocyte is critical for parasite development. Thus, validation of novel parasite invasion ligands is essential for malaria vaccine development. Recently, we demonstrated that EBP2, a Duffy binding protein (DBP) paralog, is antigenically distinct from DBP and could not be functionally inhibited by anti-DBP antibodies. Here, we took advantage of a small outbreak of P.vivax malaria, located in a non-malarious area of Brazil, to investigate for the first time IgM/IgG antibodies against EBP2 and DEKnull-2 (an engineering DBPII vaccine) among individuals who had their first and brief exposure to P.vivax (16 cases and 22 non-cases). Our experimental approach included 4 cross sectional surveys at 3-month interval (12-month follow-up). The results demonstrated that while a brief initial P.vivax infection was not efficient to induce IgM/ IgG antibodies to either EBP2 or DEKnull-2, IgG antibodies against DEKnull-2 (but not EBP2) were boosted by recurrent blood-stage infections following treatment. Of interest, in most recurrent P. vivax infections (4 out of 6 patients) DEKnull-2 IgG antibodies were sustained for 6 to 12 months. Polymorphisms in the ebp2 gene does not seem to explain EBP2 low immunogenicity as the ebp2 allele associated with the P.vivax outbreak presented high identity to the original EBP2 isolate used as recombinant protein. Although EBP2 antibodies were barely detectable after a primary episode of P.vivax infection, EBP2 was highly recognized by serum IgG from long-term malaria-exposed Amazonians (range from 35 to 92% according to previous malaria episodes). Taken together, the results showed that individuals with a single and brief exposure to P.vivax infection develop very low anti-EBP2 antibodies, which tend to increase after long-term malaria exposure. Finally, the findings highlighted the potential of DEKnull-2 as a vaccine candidate, as in non-immune individuals anti-DEKnull-2 IgG antibodies were boosted even after a brief exposure to P.vivax blood stages.

Eugenia sulcata (Myrtaceae) Nanoemulsion Enhances the Inhibitory Activity of the Essential Oil on P2X7R and Inflammatory Response In Vivo.

P2X7R is a purinergic receptor with broad expression throughout the body, especially in immune system cells. P2X7R activation causes inflammatory mediators to release, including interleukin-1ß (IL-1ß), the processing and release of which are critically dependent on this ion channel activation. P2X7R's therapeutic potential augments the discovery of new antagonistic compounds. Thus, we investigated whether the Eugenia sulcata essential oil could block P2X7R activity. The essential oil (ESO) dose-dependently inhibited ATP-promoted PI uptake and IL-1ß release with an IC50 of 113.3 ± 3.7 ng/mL and 274 ± 91 ng/mL, respectively, and the essential oil nanoemulsion (ESON) improved the ESO inhibitory effect with an IC50 of 81.4 ± 7.2 ng/mL and 62 ± 2 ng/mL, respectively. ESO and ESON reversed the carrageenan-activated peritonitis in mice, and ESON exhibited an efficacy higher than ESO. The majority substance from essential oil, ß-caryophyllene, impaired the ATP-evoked PI uptake and IL-1ß release with an IC50 value of 26 ± 0.007 ng/mL and 97 ± 0.012 ng/mL, respectively. Additionally, ß-caryophyllene reduced carrageenan-induced peritonitis, and the molecular modeling and computational simulation predicted the intermolecular interactions in the P2X7R situs. In silico, results indicated ß-caryophyllene as a potent allosteric P2X7R antagonist, although this substance may present toxic effects for humans. These data confirm the nanoemulsion of essential oil from E. sulcata as a promisor biotechnology strategy for impaired P2X7R functions and the inflammatory response.

Impressive and durable clinical responses obtained with dabrafenib and trametinib in low-grade serous ovarian cancer harbouring a BRAF V600E mutation.

Low-grade serous ovarian cancer (LGSOC) is now considered a different entity from high-grade serous ovarian cancer. The chemoresistance inherent to this type of ovarian cancer narrows the therapeutic options, especially in the recurrent setting. It is thought that the mitogen-activated protein kinase (MAPK) pathway plays a significant role in the pathogenesis of these tumours, and about 2 to 20% of LGSOC harbour a BRAF mutation. Here we present a case report of two patients with a BRAF V600E mutation that achieved sustained clinical responses with combination treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor).