Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.

Neuroserpin, IL-33 and IL-17A as potential markers of mild symptoms of depressive syndrome in Toxoplasma gondii-infected pregnant women.

Introduction: Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS. Methods: Pregnant women (n=45; age=18-39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis. Results: Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck's depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS. Discussion: Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.

Therapeutic Inducers of Natural Killer cell Killing (ThINKK): preclinical assessment of safety and efficacy in allogeneic hematopoietic stem cell transplant settings.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the standard of care for chemotherapy-refractory leukemia patients, but cure rates are still dismal. To prevent leukemia relapse following HSCT, we aim to improve the early graft-versus-leukemia effect mediated by natural killer (NK) cells. Our approach is based on the adoptive transfer of Therapeutic Inducers of Natural Killer cell Killing (ThINKK). ThINKK are expanded and differentiated from HSC, and exhibit blood plasmacytoid dendritic cell (pDC) features. We previously demonstrated that ThINKK stimulate NK cells and control acute lymphoblastic leukemia (ALL) development in a preclinical mouse model of HSCT for ALL. Here, we assessed the cellular identity of ThINKK and investigated their potential to activate allogeneic T cells. We finally evaluated the effect of immunosuppressive drugs on ThINKK-NK cell interaction. METHODS: ThINKK cellular identity was explored using single-cell RNA sequencing and flow cytometry. Their T-cell activating potential was investigated by coculture of allogeneic T cells and antigen-presenting cells in the presence or the absence of ThINKK. A preclinical human-to-mouse xenograft model was used to evaluate the impact of ThINKK injections on graft-versus-host disease (GvHD). Finally, the effect of immunosuppressive drugs on ThINKK-induced NK cell cytotoxicity against ALL cells was tested. RESULTS: The large majority of ThINKK shared the key characteristics of canonical blood pDC, including potent type-I interferon (IFN) production following Toll-like receptor stimulation. A minor subset expressed some, although not all, markers of other dendritic cell populations. Importantly, while ThINKK were not killed by allogeneic T or NK cells, they did not increase T cell proliferation induced by antigen-presenting cells nor worsened GvHD in vivo. Finally, tacrolimus, sirolimus or mycophenolate did not decrease ThINKK-induced NK cell activation and cytotoxicity. CONCLUSION: Our results indicate that ThINKK are type I IFN producing cells with low T cell activation capacity. Therefore, ThINKK adoptive immunotherapy is not expected to increase the risk of GvHD after allogeneic HSCT. Furthermore, our data predict that the use of tacrolimus, sirolimus or mycophenolate as anti-GvHD prophylaxis regimen will not decrease ThINKK therapeutic efficacy. Collectively, these preclinical data support the testing of ThINKK immunotherapy in a phase I clinical trial.

Incidência e fatores associados aos sintomas depressivos pós-parto: uma revisão de literatura / Incidence and factors associated with postpartum depressive symptoms: a literature review / Incidencia y factores asociados a los síntomas depresivos posparto: una revisión de la literatura

Objetivo: identificar na literatura científica as incidências dos sintomas depressivos pós-parto e os fatores associados. Método: revisão narrativa da literatura descrita conforme a declaração Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A busca bibliográfica foi realizada na BVS, nas bases de dados LILACS e MEDLINE. Foram elegíveis estudos observacionais com delineamento longitudinal, que utilizaram a Escala de depressão pós-parto de Edimburgo, disponíveis em texto completo, publicados nos anos de 2019 e 2020. Resultados: foram incluídos 17 artigos. A incidência de sintomatologia depressiva pós-parto variou de 0,18% a 27,87%. Os principais fatores de risco associados foram histórico de depressão, estresse e relação estressante familiar, baixo suporte social, transtornos psiquiátricos como comorbidade e experiência negativa ou complicações durante parto. Conclusão: a sintomatologia depressiva pós-parto atinge parcela expressiva das puérperas e se mantém como problema de saúde pública. Sugere-se a continuidade dos estudos que se relacionam com a temática no cenário nacional

Objective: to identify in the scientific literature the incidence of postpartum depressive symptoms and associated factors. Method: narrative review of the literature described according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The bibliographic search was carried out in the BVS, in the LILACS and MEDLINE databases. Observational studies with a longitudinal design were eligible, using the Edinburgh Postnatal Depression Scale, available in full text, published in 2019 and 2020. Results: 17 articles were included. The incidence of postpartum depressive symptoms ranged from 0.18% to 27.87%. The main associated risk factors were a history of depression, stress and stressful family relationships, low social support, comorbid psychiatric disorders and negative experiences or complications during childbirth. Conclusion: postpartum depressive symptoms affect a significant proportion of postpartum women and remain a public health problem. It is suggested that studies related to the theme be continued on a national level

Objetivos: identificar en la literatura científica la incidencia de síntomas depresivos posparto y factores asociados. Método: revisión narrativa de la literatura descrita según la declaración Preferred Reporting Items for Systematic Reviews and Meta- Analyses. La búsqueda bibliográfica se realizó en la BVS, en las bases de datos LILACS y MEDLINE. Fueron elegibles estudios observacionales con diseño longitudinal, utilizando la Escala de Depresión Postnatal de Edimburgo, disponible en texto completo, publicada en 2019 y 2020. Resultados: se incluyeron 17 artículos. La incidencia de síntomas depresivos posparto varía del 0,18% al 27,87%. Los principales factores de riesgo asociados fueron antecedentes de depresión, estrés y relaciones familiares estresantes, bajo apoyo social, trastornos psiquiátricos comórbidos y experiencias negativas o complicaciones durante el parto. Conclusion: los síntomas depresivos posparto afectan a una proporción significativa de mujeres posparto y siguen siendo un problema de salud pública. Se sugiere continuar con los estudios relacionados con el tema a nivel nacional

Incidência e fatores associados aos sintomas depressivos pós-parto: uma revisão de literatura / Incidence and factors associated with postpartum depressive symptoms: a literature review / Incidencia y factores asociados a los síntomas depresivos posparto: una revisión de la literatura

Objetivo: identificar na literatura científica as incidências dos sintomas depressivos pós-parto e os fatores associados. Método: revisão narrativa da literatura descrita conforme a declaração Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A busca bibliográfica foi realizada na BVS, nas bases de dados LILACS e MEDLINE. Foram elegíveis estudos observacionais com delineamento longitudinal, que utilizaram a Escala de depressão pós-parto de Edimburgo, disponíveis em texto completo, publicados nos anos de 2019 e 2020. Resultados: foram incluídos 17 artigos. A incidência de sintomatologia depressiva pós-parto variou de 0,18% a 27,87%. Os principais fatores de risco associados foram histórico de depressão, estresse e relação estressante familiar, baixo suporte social, transtornos psiquiátricos como comorbidade e experiência negativa ou complicações durante parto. Conclusão: a sintomatologia depressiva pós-parto atinge parcela expressiva das puérperas e se mantém como problema de saúde pública. Sugere-se a continuidade dos estudos que se relacionam com a temática no cenário nacional

Objective: to identify in the scientific literature the incidence of postpartum depressive symptoms and associated factors. Method: narrative review of the literature described according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The bibliographic search was carried out in the BVS, in the LILACS and MEDLINE databases. Observational studies with a longitudinal design were eligible, using the Edinburgh Postnatal Depression Scale, available in full text, published in 2019 and 2020. Results: 17 articles were included. The incidence of postpartum depressive symptoms ranged from 0.18% to 27.87%. The main associated risk factors were a history of depression, stress and stressful family relationships, low social support, comorbid psychiatric disorders and negative experiences or complications during childbirth. Conclusion: postpartum depressive symptoms affect a significant proportion of postpartum women and remain a public health problem. It is suggested that studies related to the theme be continued on a national level

Objetivos: identificar en la literatura científica la incidencia de síntomas depresivos posparto y factores asociados. Método: revisión narrativa de la literatura descrita según la declaración Preferred Reporting Items for Systematic Reviews and Meta- Analyses. La búsqueda bibliográfica se realizó en la BVS, en las bases de datos LILACS y MEDLINE. Fueron elegibles estudios observacionales con diseño longitudinal, utilizando la Escala de Depresión Postnatal de Edimburgo, disponible en texto completo, publicada en 2019 y 2020. Resultados: se incluyeron 17 artículos. La incidencia de síntomas depresivos posparto varía del 0,18% al 27,87%. Los principales factores de riesgo asociados fueron antecedentes de depresión, estrés y relaciones familiares estresantes, bajo apoyo social, trastornos psiquiátricos comórbidos y experiencias negativas o complicaciones durante el parto. Conclusion: los síntomas depresivos posparto afectan a una proporción significativa de mujeres posparto y siguen siendo un problema de salud pública. Se sugiere continuar con los estudios relacionados con el tema a nivel nacional.

Repurposing disulfiram, an alcohol-abuse drug, in neuroblastoma causes KAT2A downregulation and in vivo activity with a water/oil emulsion.

Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram's anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.

Alterações do sono e os fatores associados em gestantes atendidas pela atenção primária em saúde / Sleep alterations and associated factors in pregnant women attended by primary health care / Alteraciones del sueño y factores asociados en gestantes atendidas en atención primaria de salud

Resumo Contexto: A gestação ocasiona diversas mudanças fisiológicas, anatômicas, hormonais e psicológicas na mulher. As modificações gravídicas podem repercutir no sono da gestante, diminuindo sua qualidade e duração. Objetivo: Este estudo tem como objetivo verificar a prevalência de alteração do sono em gestantes e os fatores associados. Métodos: Estudo epidemiológico, transversal e analítico realizado com gestantes cadastradas nas Equipes da Estratégia de Saúde Da Família da zona urbana do município de Montes Claros no ano de 2018. A amostra, probabilística, foi calculada em 1.180 gestantes. Os dados foram coletados a partir de um questionário contendo as informações de interesse com posterior análise das variáveis. Resultados: Verificou-se que 87,5% das participantes apresentavam alterações do sono durante a gestação. O aumento do sono foi relatado por 50,5%, a diminuição por 21,8% e 15,1% ambos. O apoio social (p= 0,032), a qualidade de vida (p< 0,001), o estresse (p= 0,009) e os sintomas de depressão (p= 0,005) associaram-se individualmente com a alteração de sono e a qualidade de vida se manteve associada após ajuste (RP ajustada: 0,482, IC95% 0,482; p=<0,001). Conclusão: É elevada a alteração de sono entre as gestantes, sendo associada ao apoio social, à qualidade de vida, ao estresse e à depressão.

Abstract Background: Pregnancy causes several physiological, anatomical, hormonal and psychological changes in women. Pregnancy changes can affect the pregnant woman's sleep, reducing its quality and duration. Objective: This study aims to verify the prevalence of sleep alterations and associated factors in pregnant women. Methods: Epidemiological, cross-sectional and analytical study carried out with pregnant women registered in the Family Health Strategy Teams of the urban area of the municipality of Montes Claros in 2018. The probabilistic sample was calculated in 1,180 pregnant women. Data were collected from a questionnaire containing the information of interest with subsequent analysis of the variables. Results: It was verified that 87.5% of the participants had sleep alterations during pregnancy. The increase in sleep was reported by 50.5%, the decrease by 21.8% and 15.1% both. Social support (p=0.032), quality of life (p<0.001), stress (p=0.009) and symptoms of depression (p=0.005) were individually associated with sleep disturbance and quality of life was remained associated after adjustment (adjusted PR: 0.482, 95% CI 0.482; p=<0.001). Conclusion: There is a high sleep disturbance among pregnant woman, being associated with social support, quality of life, stress and depression.

Resumen Contexto: El embarazo provoca diversos cambios fisiológicos, anatómicos, hormonales y psicológicos en la mujer. Los cambios del embarazo pueden afectar el sueño de la mujer embarazada, reduciendo su calidad y duración. Objetivo: Este estudio tiene como objetivo verificar la prevalencia de trastornos del sueño en mujeres embarazadas y los factores asociados. Métodos: Estudio epidemiológico, transversal y analítico realizado con gestantes registradas en los Equipos de Estrategia de Salud de la Familia del casco urbano del municipio de Montes Claros en el año 2018. La muestra probabilística se calculó en 1.180 gestantes. Los datos se recogieron a partir de un cuestionario que contenía la información de interés con el posterior análisis de las variables. Resultados: Se encontró que 87,5% de las participantes presentaron trastornos del sueño durante el embarazo. El aumento del sueño fue reportado en un 50,5%, la disminución en un 21,8% y en un 15,1% ambos. El apoyo social (p=0,032), la calidad de vida (p<0,001), el estrés (p=0,009) y los síntomas de depresión (p=0,005) se asociaron individualmente con la alteración del sueño y la calidad de vida se mantuvo asociada después del ajuste (RP ajustado: 0,482, IC 95% 0,482, p=<0,001). Conclusión: Existe una alta alteración del sueño entre las gestantes, siendo asociado al apoyo social, calidad de vida, estrés y depresión.

Fatores associados ao diagnóstico da sífilis adquirida em usuários de um centro de testagem e aconselhamento / Factors associated with the diagnosis of acquired syphilis in users of a testing and counseling center / Factores asociados al diagnóstico de sífilis adquirida en usuarios de un centro de pruebas y asesoramiento

Objetivo: analisar a frequência de sífilis entre os usuários do Centro de Testagem e Aconselhamento de Montes Claros, Minas Gerais, e os fatores associados à infecção. Método: trata-se de um estudo transversal, com componentes descritivos e analíticos, realizado com usuários atendidos no serviço entre 2014 e 2019. Os dados foram coletados de fonte secundária, por amostragem aleatória e sistemática. Resultados: a amostra foi composta por 957 formulários de usuários e a frequência de casos de testes rápidos reagentes para sífilis foi de 11,3%, com distribuição semelhante entre os sexos. O diagnóstico da sífilis se associou de forma significativa às variáveis: situação conjugal, idade, escolaridade, quantidade de parcerias sexuais, orientação sexual e uso de drogas no último ano. Conclusão: programas de aconselhamento e testagem rápida devem ser incentivados para prevenção e diminuição das infecções sexualmente transmissíveis em Montes Claros e em todo país

Objective: to analyze the frequency of syphilis among users of the Testing and Counseling Center in Montes Claros, Minas Gerais, and the factors associated with the infection. Method: this is a cross-sectional study, with descriptive and analytical components, carried out with users seen at the service between 2014 and 2019. Data were collected from a secondary source, by random and systematic sampling. Results: the sample consisted of 957 user forms and the frequency of cases of rapid reactive tests for syphilis was 11.3%, with similar distribution between genders. The diagnosis of syphilis was significantly associated with the variables: marital status, age, education, number of sexual partners, sexual orientation and drug use in the last year. Conclusion:counseling and rapid testing programs should be encouraged to prevent and reduce sexually transmitted infections in Montes Claros and across the country

Objetivo: analizar la frecuencia de sífilis entre los usuarios del Centro de Asesoramiento y Pruebas en Montes Claros, Minas Gerais y los factores asociados a la infección. Método: se trata de un estudio transversal, con componentes descriptivos y analíticos, realizado con usuarios atendidos en el servicio entre 2014 y 2019. Los datos se recolectaron de una fuente secundaria, mediante muestreo aleatorio y sistemático. Resultados: la muestra estuvo conformada por 957 formularios de usuario y la frecuencia de casos de pruebas reactivas rápidas para sífilis fue de 11,3%, con distribución similar entre géneros. El diagnóstico de sífilis se asoció significativamente con las variables: estado civil, edad, educación, número de parejas sexuales, orientación sexual. y consumo de drogas en el último año. Conclusión: se deben fomentar los programas de asesoramiento y pruebas rápidas para prevenir y reducir las infecciones de transmisión sexual en Montes Claros y en todo el país

Colonic pseudotumor caused by abdominal actinomycosis: A case report.

We report a case of abdominal actinomycosis, a chronic suppurative infection caused by bacteria of the genus Actinomyces, simulating colon cancer, and presenting with abdominal pain and leukocytosis. Computed tomography revealed a mass lesion with irregular contours, infiltrative aspect, with extension to omental fat and abdominal wall, in the transverse colon. A surgical intervention was performed due to the suspicious of a colonic tumor. In the post-operative period, anatomopathological examination showed suppurative nodules associated with actinomycetes colonies, confirming the diagnosis of abdominal actinomycosis. After surgery, the patient was submitted to antibiotic treatment and no relapse was observed.

Reportamos un caso de actinomicosis abdominal, una infección supurativa crónica causada por bacterias del genero Actinomyces, que simula el cáncer de colon y se manifiesta con dolor abdominal y leucocitosis. La tomografía computada reveló una lesión sólida con contornos irregulares y aspecto infiltrativo en el colon transverso, con extensión al epiplón y la pared abdominal. La intervención quirúrgica fue realizada debido a la sospecha de un tumor de colon. En el posoperatorio, el examen anatomopatológico mostró la presencia de nódulos supurativos asociados con colonias de actinomicetos, lo que confirma el diagnóstico de actinomicosis abdominal. Posteriormente a la cirugía el paciente recibió antibioticoterapia y no presentó Recidivas.

Patients' NK cell stimulation with activated plasmacytoid dendritic cells increases dinutuximab-induced neuroblastoma killing.

Targeted immunotherapy has improved the outcome of patients with high-risk neuroblastoma (NB). However, immune escape of tumor cells still occurs and about 40% of NB patients relapse and die from their disease. We previously showed that natural killer (NK) cell stimulation by Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC) increases the efficacy of dinutuximab-based immunotherapy against NB cell lines via the TRAIL death-receptor pathway. With the aim to translate our findings into a novel adoptive therapy of TLR-activated pDC, we investigated the pDC/NK cell axis in NB patients undergoing dinutuximab-based immunotherapy. We show that pDC counts were low at the beginning of immunotherapy but reached normal levels over time. Blood NK cell counts were normal in all patients, although a high proportion of CD56bright CD16low/- cells was observed. The stimulation of patient's blood cells with a TLR9 ligand led to IFN-α production by pDC, and TRAIL expression on NK cell surface. Patient's NK cells expressed high levels of CD69 and TRAIL after stimulation with activated pDC. Both CD56bright CD16low/- and CD56dim CD16+ NK cells degranulated against autologous target cells in the presence of dinutuximab. Importantly, pDC-induced NK cell activation increased the dinutuximab mediated autologous killing of patient-derived NB cells. Altogether, our study demonstrates that TLR-activated pDC strongly increase the cytotoxic functions of NK cells in high-risk NB patients undergoing immunotherapy. These results, therefore, support pDC adoptive immunotherapy as a novel approach to decrease the risk of relapse in patients with high-risk NB.

Antimicrobial activity of Phyllanthus amarus Schumach. & Thonn and inhibition of the NorA efflux pump of Staphylococcus aureus by Phyllanthin.

The aim of this study was to evaluate the antimicrobial activity of ethanoic extract of P. amarus (PAEE) and its compound Phyllanthin, as well as, investigate if these natural products could modulate the fluoroquinolone-resistance in S. aureus SA1199-B by way of overexpression of the NorA efflux pump. Microdilution tests were carried out to determine the minimal inhibitory concentration (MIC) of the PAEE or Phyllanthin against several bacterial and yeast strains. To evaluate if PAEE or Phyllanthin were able to act as modulators of the fluoroquinolone-resistance, MICs for Norfloxacin and ethidium bromide were determined in the presence or absence of PAEE or Phyllanthin against S. aureus SA1199-B. PAEE showed antimicrobial activity against Gram-negative strains, meanwhile Phyllanthin was inactive against all strains tested. Addition of PAEE or Phyllanthin, to the growth media at sub-inhibitory concentrations enhanced the activity of the Norfloxacin as well as, Ethidium Bromide, against S. aureus SA1199-B. These results indicate that Phyllanthin is able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. This hypothesis was supported by in silico docking analysis which confirmed that Phyllantin is a NorA ligand. Thus, this compound could be used as a potentiating agent of the Norfloxacin activity in the treatment of infections caused by fluoroquinolone-resistant S. aureus.

Anaerobic co-digestion of coffee husks and microalgal biomass after thermal hydrolysis.

Residual coffee husks after seed processing may be better profited if bioconverted into energy through anaerobic digestion. This process may be improved by implementing a pretreatment step and by co-digesting the coffee husks with a more liquid biomass. In this context, this study aimed at evaluating the anaerobic co-digestion of coffee husks with microalgal biomass. For this, both substrates were pretreated separately and in a mixture for attaining 15% of total solids (TS), which was demonstrated to be the minimum solid content for pretreatment of coffee husks. The results showed that the anaerobic co-digestion presented a synergistic effect, leading to 17% higher methane yield compared to the theoretical value of both substrates biodegraded separately. Furthermore, thermal hydrolysis pretreatment increased coffee husks anaerobic biodegradability. For co-digestion trials, the highest values were reached for pretreatment at 120 °C for 60 min, which led to 196 mLCH4/gVS and maximum methane production rate of 0.38 d-1.

ATLANTIC BIRDS: a data set of bird species from the Brazilian Atlantic Forest.

South America holds 30% of the world's avifauna, with the Atlantic Forest representing one of the richest regions of the Neotropics. Here we have compiled a data set on Brazilian Atlantic Forest bird occurrence (150,423) and abundance samples (N = 832 bird species; 33,119 bird individuals) using multiple methods, including qualitative surveys, mist nets, point counts, and line transects). We used four main sources of data: museum collections, on-line databases, literature sources, and unpublished reports. The data set comprises 4,122 localities and data from 1815 to 2017. Most studies were conducted in the Florestas de Interior (1,510 localities) and Serra do Mar (1,280 localities) biogeographic sub-regions. Considering the three main quantitative methods (mist net, point count, and line transect), we compiled abundance data for 745 species in 576 communities. In the data set, the most frequent species were Basileuterus culicivorus, Cyclaris gujanensis, and Conophaga lineata. There were 71 singletons, such as Lipaugus conditus and Calyptura cristata. We suggest that this small number of records reinforces the critical situation of these taxa in the Atlantic Forest. The information provided in this data set can be used for macroecological studies and to foster conservation strategies in this biodiversity hotspot. No copyright restrictions are associated with the data set. Please cite this Data Paper if data are used in publications and teaching events.

Steam explosion pretreatment improved the biomethanization of coffee husks.

This study evaluated the potential of energy generation using a combined heat and power co-generation system (CHP) from biogas produced during the anaerobic digestion of coffee husks (CH) pretreated with steam explosion. Pretreatment conditions assessed were time (1, 5, 15 and 60min) and temperature (120, 180 and 210°C). Polysaccharides solubilisation and biogas production were not correlated. While pretreatment with severities higher than 4 resulted in a highest solubilisation of cellulose, hemicelluloses and lignin; however, furans concentration in those cases hindered biomass biodegradation. Considering a CHP, all pretreatment conditions were worthwhile when compared to non-pretreated CH. The best condition was 120°C for 60min, in which a 2.37 severity showed the highest methane yield (144.96NmLCH4gCOD-1) and electricity production (0.59kWhkgCH-1). However, even better results could be achieved using 120°C for only 5min, which would lead to a larger amount of CH daily processed.

In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells.

Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34+ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 108 pDC can be produced from a typical cord blood unit. Blocking the aryl hydrocarbon receptor (AHR) pathway significantly increased the yield of pDC. When compared to pDC isolated from peripheral blood, in vitro differentiated pDC (ivD-pDC) exhibited an increased capacity to induce NK cell-mediated killing of ALL. Although ivD-pDC produced lower amounts of IFN-α than peripheral blood pDC upon TLR activation, they produced more IFN-λ2, known to play a critical role in the induction of anti-tumoral NK cell functions. Both TLR-9 and TLR-7 ligands triggered pDC-induced NK cell activation, offering the possibility to use any clinical-grade TLR-7 or TLR-9 ligands in future clinical trials. Finally, adoptive transfer of ivD-pDC cultured in the presence of an AHR antagonist cured humanized mice with minimal ALL disease. Collectively, our results pave the way to clinical-grade production of sufficient numbers of human pDC for innate immunotherapy against ALL and other refractory malignancies.

Efficient Killing of High Risk Neuroblastoma Using Natural Killer Cells Activated by Plasmacytoid Dendritic Cells.

High-risk neuroblastoma (NB) remains a major therapeutic challenge despite the recent advent of disialoganglioside (GD2)-antibody treatment combined with interleukin (IL)-2 and granulocyte monocyte-colony stimulating factor (GM-CSF). Indeed, more than one third of the patients still die from this disease. Here, we developed a novel approach to improve the current anti-GD2 immunotherapy based on NK cell stimulation using toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDCs). We demonstrated that this strategy led to the efficient killing of NB cells. When the expression of GD2 was heterogeneous on NB cells, the combination of pDC-mediated NK-cell activation and anti-GD2 treatment significantly increased the cytotoxicity of NK cells against NB cells. Activation by pDCs led to a unique NK-cell phenotype characterized by increased surface expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with increased expression of CD69 on CD56dim cytotoxic cells, and strong interferon-γ production. Additionally, NB-cell killing was mediated by the TRAIL death-receptor pathway, as well as by the release of cytolytic granules via the DNAX accessory molecule 1 pathway. NK-cell activation and lytic activity against NB was independent of cell contact, depended upon type I IFN produced by TLR-9-activated pDCs, but was not reproduced by IFN-α stimulation alone. Collectively, these results highlighted the therapeutic potential of activated pDCs for patients with high-risk NB.

Analysis of the learning curve for transurethral resection of the prostate. Is there any influence of musical instrument and video game skills on surgical performance?

OBJECTIVE: To evaluate the learning curve for transurethral resection of the prostate (TURP) among urology residents and study the impact of video game and musical instrument playing abilities on its performance. MATERIAL AND METHODS: A prospective study was performed from July 2009 to January 2013 with patients submitted to TURP for benign prostatic hyperplasia. Fourteen residents operated on 324 patients. The following parameters were analyzed: age, prostate-specific antigen levels, prostate weight on ultrasound, pre- and postoperative serum sodium and hemoglobin levels, weight of resected tissue, operation time, speed of resection, and incidence of capsular lesions. Gender, handedness, and prior musical instrument and video game playing experience were recorded using survey responses. RESULTS: The mean resection speed in the first 10 procedures was 0.36 g/min and reached a mean of 0.51 g/min after the 20(th) procedure. The incidence of capsular lesions decreased progressively. The operation time decreased progressively for each subgroup regardless of the difference in the weight of tissue resected. Those experienced in playing video games presented superior resection speed (0.45 g/min) when compared with the novice (0.35 g/min) and intermediate (0.38 g/min) groups (p=0.112). Musical instrument playing abilities did not affect the surgical performance. CONCLUSION: Speed of resection, weight of resected tissue, and percentage of resected tissue improve significantly and the incidence of capsular lesions reduces after the performance of 10 TURP procedures. Experience in playing video games or musical instruments does not have a significant effect on outcomes.

TRAIL-mediated killing of acute lymphoblastic leukemia by plasmacytoid dendritic cell-activated natural killer cells.

Acute lymphoblastic leukemia (ALL) still frequently recurs after hematopoietic stem cell transplantation (HSCT), underscoring the need to improve the graft-versus-leukemia (GvL) effect. Natural killer (NK) cells reconstitute in the first months following HSCT when leukemia burden is at its lowest, but ALL cells have been shown to be resistant to NK cell-mediated killing. We show here that this resistance is overcome by NK cell stimulation with TLR-9-activated plasmacytoid dendritic cells (pDCs). NK cell priming with activated pDCs resulted in TRAIL and CD69 up-regulation on NK cells and IFN-γ production. NK cell activation was dependent on IFN-α produced by pDCs, but was not reproduced by IFN-α alone. ALL killing was further enhanced by inhibition of KIR engagement. We showed that ALL lysis was mainly mediated by TRAIL engagement, while the release of cytolytic granules was involved when ALL expressed NK cell activating receptor ligands. Finally, adoptive transfers of activated-pDCs in ALL-bearing humanized mice delayed the leukemia onset and cure 30% of mice. Our data therefore demonstrate that TLR-9 activated pDCs are a powerful tool to overcome ALL resistance to NK cell-mediated killing and to reinforce the GvL effect of HSCT. These results open new therapeutic avenues to prevent relapse in children with ALL.

Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy.

Plasmacytoid dendritic cells (pDCs) initiate both innate and adaptive immune responses, making them attractive targets for post-transplantation immunotherapy, particularly after cord blood transplantation (CBT). Toll-like receptor (TLR) agonists are currently studied for pDC stimulation in various clinical settings. Their efficacy depends on pDC number and functionality, which are unknown after CBT. We performed a longitudinal study of pDC reconstitution in children who underwent bone marrow transplantation (BMT) and single-unit CBT. Both CBT and unrelated BMT patients received antithymocyte globulin as part of their graft-versus-host disease prophylaxis regimen. pDC blood counts were higher in CBT patients than in healthy volunteers from 2 to 9 months after transplantation, whereas they remained lower in BMT patients. We showed that cord blood progenitors gave rise in vitro to a 500-fold increase in functional pDCs over bone marrow counterparts. Upon stimulation with a TLR agonist, pDCs from both CBT and BMT recipients upregulated T cell costimulatory molecules, whereas interferon-alpha (IFN-α) production was impaired for 9 months after CBT. TLR agonist treatment is thus not expected to induce IFN-α production by pDCs after CBT, limiting its immunotherapeutic potential. Fortunately, in vitro production of large amounts of functional pDCs from cord blood progenitors paves the way for the post-transplantation adoptive transfer of pDCs.

Interactions between lower urinary tract symptoms and cardiovascular risk factors determine distinct patterns of erectile dysfunction: a latent class analysis.

PURPOSE: An epidemiological association between lower urinary tract symptoms and erectile dysfunction is well established. However, interactions among multiple risk factors and the role of each in pathological mechanisms are not fully elucidated MATERIALS AND METHODS: We enrolled 898 men undergoing prostate cancer screening for evaluation with the International Prostate Symptom Score (I-PSS) and simplified International Index of Erectile Function-5 (IIEF-5) questionnaires. Age, race, hypertension, diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, serum hormones and anthropometric parameters were also evaluated. Risk factors for erectile dysfunction were identified by logistic regression. The 333 men with at least mild to moderate erectile dysfunction (IIEF 16 or less) were included in a latent class model to identify relationships across erectile dysfunction risk factors. RESULTS: Age, hypertension, diabetes, lower urinary tract symptoms and cardiovascular event were independent predictors of erectile dysfunction (p<0.05). We identified 3 latent classes of patients with erectile dysfunction (R2 entropy=0.82). Latent class 1 had younger men at low cardiovascular risk and a moderate/high prevalence of lower urinary tract symptoms. Latent class 2 had the oldest patients at moderate cardiovascular risk with an increased prevalence of lower urinary tract symptoms. Latent class 3 had men of intermediate age with the highest prevalence of cardiovascular risk factors and lower urinary tract symptoms. Erectile dysfunction severity and lower urinary tract symptoms increased from latent class 1 to 3. CONCLUSIONS: Risk factor interactions determined different severities of lower urinary tract symptoms and erectile dysfunction. The effect of lower urinary tract symptoms and cardiovascular risk outweighed that of age. While in the youngest patients lower urinary tract symptoms acted as a single risk factor for erectile dysfunction, the contribution of vascular disease resulted in significantly more severe dysfunction. Applying a risk factor interaction model to prospective trials could reveal distinct classes of drug responses and help define optimal treatment strategies for specific groups.