Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS.

BACKGROUND: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment. PATIENTS AND METHODS: Patients with nmCRPC were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval-specific new and cumulative event rates were determined during the first 24 months of the double-blind period. RESULTS: Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and ≤2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months. CONCLUSION: Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment-related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment. TRIAL NUMBER: ClinicalTrials.gov identifier NCT02200614.

Cognitive-behavioral program to control lower urinary tract symptoms after radical prostatectomy: a randomized clinical trial.

OBJECTIVE: to assess the effectiveness of a cognitive-behavioral program to control lower urinary tract symptoms after radical prostatectomy. METHODS: a randomized clinical trial study, with 41 participants randomized into intervention (n=20) and control (n=21), for three months. The intervention group received the cognitive-behavioral program, while the control group received routine guidance from the service. Outcome variables were urinary incontinence intensity and lower urinary tract symptoms, assessed by the Pad-Test and Urinary Incontinence Scale of Radical Prostatectomy and King's Health Questionnaire. RESULTS: at the end of the study, the intervention group had a lower urinary incontinence intensity (p≤0.001), and there were less chances of presenting changes in urinary frequency (p≤0.001), urinary urgency (p≤0.001), nocturia (p=0.005), stress urinary incontinence (p≤0.001) and urge incontinence (p≤0.045). CONCLUSION: the cognitive-behavioral program was effective in reducing lower urinary tract symptoms after radical prostatectomy. Brazilian Clinical Trial Registry: RBR-3sstqg.

Cognitive-behavioral program to control lower urinary tract symptoms after radical prostatectomy: a randomized clinical trial / Programa cognitivo-conductual para el control de los síntomas del tracto urinario inferior después de la prostatectomía radical: un ensayo clínico aleatorizado / Programa cognitivo-comportamental para controle de sintomas do trato urinário inferior pós-prostatectomia radical: ensaio clínico randomizado

ABSTRACT Objective: to assess the effectiveness of a cognitive-behavioral program to control lower urinary tract symptoms after radical prostatectomy. Methods: a randomized clinical trial study, with 41 participants randomized into intervention (n=20) and control (n=21), for three months. The intervention group received the cognitive-behavioral program, while the control group received routine guidance from the service. Outcome variables were urinary incontinence intensity and lower urinary tract symptoms, assessed by the Pad-Test and Urinary Incontinence Scale of Radical Prostatectomy and King's Health Questionnaire. Results: at the end of the study, the intervention group had a lower urinary incontinence intensity (p≤0.001), and there were less chances of presenting changes in urinary frequency (p≤0.001), urinary urgency (p≤0.001), nocturia (p=0.005), stress urinary incontinence (p≤0.001) and urge incontinence (p≤0.045). Conclusion: the cognitive-behavioral program was effective in reducing lower urinary tract symptoms after radical prostatectomy. Brazilian Clinical Trial Registry: RBR-3sstqg.

RESUMEN Objetivo: evaluar la efectividad de un programa cognitivo-conductual para controlar los síntomas del tracto urinario inferior después de la prostatectomía radical. Métodos: estudio de ensayo clínico aleatorizado, con 41 participantes aleatorizados en intervención (n=20) y control (n=21), durante tres meses. El grupo de intervención recibió el programa cognitivo-conductual, mientras que el grupo control recibió orientación rutinaria del servicio. Las variables de resultado fueron la intensidad de la incontinencia urinaria y los síntomas del tracto urinario inferior, evaluados mediante Pad-Test y Urinary Incontinence Scale of Radical Prostatectomy y King's Health Questionnaire. Resultados: al final del estudio, el grupo intervención presentó menor intensidad de incontinencia urinaria (p≤0,001), y hubo menos posibilidades de presentar cambios en la frecuencia urinaria (p≤0,001), urgencia urinaria (p≤0,001), nicturia (p=0,005), incontinencia urinaria de esfuerzo (p≤0,001) e incontinencia de urgencia (p≤0,045). Conclusión: el programa cognitivo-conductual fue eficaz para reducir los síntomas del tracto urinario inferior después de la prostatectomía radical. Registro Brasileño de Ensayos Clínicos: RBR-3sstqg.

RESUMO Objetivo: avaliar a efetividade de um programa cognitivo-comportamental para controle de sintomas do trato urinário inferior pós-prostatectomia radical. Método: estudo de ensaio clínico randomizado, com 41 participantes aleatorizados em intervenção (n=20) e controle (n=21), durante três meses. O grupo intervenção recebeu o programa cognitivo-comportamental, enquanto o grupo controle recebeu orientações de rotina do serviço. As variáveis desfechos foram intensidade da incontinência urinária e sintomas do trato urinário inferior, avaliados pelo Pad-Test e Urinary Incontinence Scale of Radical Prostatectomy e King's Health Questionnaire. Resultados: ao final do estudo, o grupo intervenção apresentou menor intensidade da incontinência urinária (p≤0,001), e houve menos chances de apresentar alterações da frequência urinária (p≤0,001), urgência miccional (p≤0,001), noctúria (p=0,005), incontinência urinária de esforço (p≤0,001) e urge-incontinência (p≤0,045). Conclusão: o programa cognitivo-comportamental foi efetivo para a redução de sintomas do trato urinário inferior após a prostatectomia radical. Registro Brasileiro de Ensaios Clínicos: RBR-3sstqg.

Metarhizium anisopliae blastospores are highly virulent to adult Aedes aegypti, an important arbovirus vector.

BACKGROUND: The use of entomopathogenic fungi (EPF) for the control of adult mosquitoes is a promising alternative to synthetic insecticides. Previous studies have only evaluated conidiospores against adult mosquitoes. However, blastospores, which are highly virulent against mosquito larvae and pupae, could also be effective against adults. METHODS: Metarhizium anisopliae (ESALQ 818 and LEF 2000) blastospores and conidia were first tested against adult Aedes aegypti by spraying insects with spore suspensions. Blastospores were then tested using an indirect contact bioassay, exposing mosquitoes to fungus-impregnated cloths. Virulence when using blastospores suspended in 20% sunflower oil was also investigated. RESULTS: Female mosquitoes sprayed with blastospores or conidia at a concentration of 108 propagules ml-1 were highly susceptible to both types of spores, resulting in 100% mortality within 7 days. However, significant differences in virulence of the isolates and propagules became apparent at 107 spores ml-1, with ESALQ 818 blastospores being more virulent than LEF 2000 blastospores. ESALQ 818 blastospores were highly virulent when mosquitoes were exposed to black cotton cloths impregnated with blastospores shortly after preparing the suspensions, but virulence declined rapidly 12 h post-application. The addition of vegetable oil to blastospores helped maintain virulence for up to 48 h. CONCLUSION: The results showed that blastospores were more virulent to adult female Ae. aegypti than conidia when sprayed onto the insects or applied to black cloths. Vegetable oil helped maintain blastospore virulence. The results show that blastospores have potential for use in integrated vector management, although new formulations and drying techniques need to be investigated.

Another Piece of the Puzzle: Echinococcus oligarthrus Recorded in Jaguarundis (Herpailurus yagouaroundi) in Southern Brazil.

Echinococcus oligarthrus is a tapeworm endemic to South America and widely distributed in the Amazon region. Its lifecycle is maintained by relationships between felids and their prey, mainly small sylvatic rodents, but humans can be infected occasionally. We report two female jaguarundis (Herpailurus yagouaroundi) harboring E. oligarthrus in southern Brazil. The felines were found road killed in periurban areas, and, during necropsy, the small intestine was examined. Visual inspection revealed helminths, which were submitted to microscopy and molecular examination. Morphologically, they were around 2.5 mm long, with four suckers and an armed scolex with two rows of hooks. Phylogenetic reconstruction using cytochrome c oxidase subunit I gene sequences placed samples from south Brazil in the same clade as all other E. oligarthrus samples, but as a sister group. Genetic distance gave similar results, resulting in a divergence of 0.087% between the samples described in this study and other samples. The geographic pattern of genetic diversity, as assessed by analysis of molecular variance, suggests that the divergency results from isolation by distance. This finding expands the geographic range of E. oligarthrus and brings new insights to help understand and prevent the zoonosis it causes.

Clinical, laboratory, and functional characteristics of asthma-COPD overlap in patients with a primary diagnosis of COPD / Características clínicas, laboratoriais e funcionais da sobreposição asma-DPOC em pacientes previamente diagnosticados com DPOC

ABSTRACT Objective: To evaluate the frequency of asthma-COPD overlap (ACO) in patients with COPD and to compare, from a clinical, laboratory, and functional point of view, patients with and without ACO, according to different diagnostic criteria. Methods: The participants underwent evaluation by a pulmonologist, together with spirometry and blood tests. All of the patients were instructed to record their PEF twice a day. The diagnosis of ACO was based on the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar (PLATINO, Latin American Project for the Investigation of Obstructive Lung Disease) criteria, the American Thoracic Society (ATS) Roundtable criteria, and the Spanish criteria. We investigated patient histories of exacerbations and hospitalizations, after which we applied the COPD Assessment Test and the modified Medical Research Council scale, to classify risk and symptoms in accordance with the GOLD criteria. Results: Of the 51 COPD patients, 14 (27.5%), 8 (12.2%), and 18 (40.0) were diagnosed with ACO on the basis of the PLATINO, ATS Roundtable, and Spanish criteria, respectively. The values for pre-bronchodilator FVC, post-bronchodilator FVC, and pre-bronchodilator FEV1 were significantly lower among the patients with ACO than among those with COPD only (1.9 ± 0.4 L vs. 2.4 ± 0.7 L, 2.1 ± 0.5 L vs. 2.5 ± 0.8 L, and 1.0 ± 0.3 L vs. 1.3 ± 0.5 L, respectively). When the Spanish criteria were applied, IgE levels were significantly higher among the patients with ACO than among those with COPD only (363.7 ± 525.9 kU/L vs. 58.2 ± 81.6 kU/L). A history of asthma was more common among the patients with ACO (p < 0.001 for all criteria). Conclusions: In our sample, patients with ACO were more likely to report previous episodes of asthma and had worse lung function than did those with COPD only. The ATS Roundtable criteria appear to be the most judicious, although concordance was greatest between the PLATINO and the Spanish criteria.

RESUMO Objetivo: Avaliar a frequência de asthma-COPD overlap (ACO, sobreposição asma-DPOC) em pacientes com DPOC e comparar, do ponto de vista clínico, laboratorial e funcional, os pacientes com e sem essa sobreposição conforme diferentes critérios diagnósticos. Métodos: Os participantes foram submetidos à avaliação com pneumologista, espirometria e exame sanguíneo, sendo orientados a manter o registro do PFE duas vezes ao dia. O diagnóstico de ACO deu-se através dos critérios Projeto Latino-Americano de Investigação em Obstrução Pulmonar (PLATINO), American Thoracic Society (ATS) Roundtable e Espanhol. Foram investigados os históricos de exacerbações e hospitalizações e aplicados os instrumentos COPD Assessment Test e escala Medical Research Council modificada, utilizados para a classificação de risco e sintomas da GOLD. Resultados: Entre os 51 pacientes com DPOC, 14 (27,5%), 8 (12,2%) e 18 (40,0) foram diagnosticados com ACO segundo os critérios PLATINO, ATS Roundtable e Espanhol, respectivamente. Pacientes com sobreposição significativamente apresentaram pior CVF pré-broncodilatador (1,9 ± 0,4 L vs. 2,4 ± 0,7 L), CVF pós-broncodilatador (2,1 ± 0,5 L vs. 2,5 ± 0,8 L) e VEF1 pré-broncodilatador (1,0 ± 0,3 L vs. 1,3 ± 0,5 L) quando comparados a pacientes com DPOC. Os níveis de IgE foram significativamente mais elevados em pacientes com sobreposição diagnosticados pelo critério Espanhol (363,7 ± 525,9 kU/L vs. 58,2 ± 81,6 kU/L). O histórico de asma foi mais frequente em pacientes com a sobreposição (p < 0,001 para todos os critérios). Conclusões: Nesta amostra, pacientes com ACO relataram asma prévia com maior frequência e possuíam pior função pulmonar quando comparados a pacientes com DPOC. O critério ATS Roundtable aparenta ser o mais criterioso em sua definição, enquanto os critérios PLATINO e Espanhol apresentaram maior concordância entre si.

Clinical, laboratory, and functional characteristics of asthma-COPD overlap in patients with a primary diagnosis of COPD.

OBJECTIVE: To evaluate the frequency of asthma-COPD overlap (ACO) in patients with COPD and to compare, from a clinical, laboratory, and functional point of view, patients with and without ACO, according to different diagnostic criteria. METHODS: The participants underwent evaluation by a pulmonologist, together with spirometry and blood tests. All of the patients were instructed to record their PEF twice a day. The diagnosis of ACO was based on the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar (PLATINO, Latin American Project for the Investigation of Obstructive Lung Disease) criteria, the American Thoracic Society (ATS) Roundtable criteria, and the Spanish criteria. We investigated patient histories of exacerbations and hospitalizations, after which we applied the COPD Assessment Test and the modified Medical Research Council scale, to classify risk and symptoms in accordance with the GOLD criteria. RESULTS: Of the 51 COPD patients, 14 (27.5%), 8 (12.2%), and 18 (40.0) were diagnosed with ACO on the basis of the PLATINO, ATS Roundtable, and Spanish criteria, respectively. The values for pre-bronchodilator FVC, post-bronchodilator FVC, and pre-bronchodilator FEV1 were significantly lower among the patients with ACO than among those with COPD only (1.9 ± 0.4 L vs. 2.4 ± 0.7 L, 2.1 ± 0.5 L vs. 2.5 ± 0.8 L, and 1.0 ± 0.3 L vs. 1.3 ± 0.5 L, respectively). When the Spanish criteria were applied, IgE levels were significantly higher among the patients with ACO than among those with COPD only (363.7 ± 525.9 kU/L vs. 58.2 ± 81.6 kU/L). A history of asthma was more common among the patients with ACO (p < 0.001 for all criteria). CONCLUSIONS: In our sample, patients with ACO were more likely to report previous episodes of asthma and had worse lung function than did those with COPD only. The ATS Roundtable criteria appear to be the most judicious, although concordance was greatest between the PLATINO and the Spanish criteria.

Aedes aegypti (Diptera: Culicidae) Immune Responses with Different Feeding Regimes Following Infection by the Entomopathogenic Fungus Metarhizium anisopliae.

The mosquito Aedes aegypti is the most notorious vector of illness-causing viruses. The use of entomopathogenic fungi as bioinsecticides is a promising alternative for the development of novel mosquito control strategies. We investigate whether differences in immune responses could be responsible for modifications in survival rates of insects following different feeding regimes. Sucrose and blood-fed adult A. aegypti females were sprayed with M. anisopliae 1 × 106 conidia mL-1, and after 48 h, the midgut and fat body were dissected. We used RT-qPCR to monitor the expression of Cactus and REL1 (Toll pathway), IMD, REL2, and Caspar (IMD pathway), STAT and PIAS (JAK-STAT pathway), as well as the expression of antimicrobial peptides (Defensin A, Attacin and Cecropin G). REL1 and REL2 expression in both the midgut and fat body were higher in blood-fed fungus-challenged A. aegypti than in sucrose-fed counterparts. Interestingly, infection of sucrose-fed insects induced Cactus expression in the fat body, a negative regulator of the Toll pathway. The IMD gene was upregulated in the fat body in response to fungal infection after a blood meal. Additionally, we observed the induction of antimicrobial peptides in the blood-fed fungus-challenged insects. This study suggests that blood-fed A. aegypti are less susceptible to fungal infection due to the rapid induction of Toll and IMD immune pathways.

Neem oil increases the persistence of the entomopathogenic fungus Metarhizium anisopliae for the control of Aedes aegypti (Diptera: Culicidae) larvae.

BACKGROUND: The entomopathogenic fungus Metarhizium anisopliae is a candidate for the integrated management of the disease vector mosquito Aedes aegypti. Metarhizium anisopliae is pathogenic and virulent against Ae. aegypti larvae; however, its half-life is short without employing adjuvants. Here, we investigated the use of neem oil to increase virulence and persistence of the fungus under laboratory and simulated field conditions. METHODS: Neem was mixed with M. anisopliae and added to recipients. Larvae were then placed in recipients at 5-day intervals for up to 50 days. Survival rates were evaluated 7 days after exposing larvae to each treatment. The effect of neem on conidial germination following exposure to ultraviolet radiation was evaluated under laboratory conditions. Statistical tests were carried out using ANOVA and regression analysis. RESULTS: Laboratory bioassays showed that the fungus alone reduced survival to 30% when larvae were exposed to the treatment as soon as the suspension had been prepared (time zero). A mixture of fungus + neem resulted in 11% survival at time zero. The combination of fungus + neem significantly reduced larval survival rates even when suspensions had been maintained for up to 45 days before adding larvae. For simulated-field experiments 1% neem was used, even though this concentration is insecticidal, resulting in 20% survival at time zero. However, this toxic effect was reduced over time. When used alone under simulated-field conditions the fungus rapidly lost virulence. The formulation fungus + neem effectively maintained fungal virulence, with larval survival rates significantly reduced for up to 45 days after preparation of the suspensions. The effective half-life of the fungus or neem when used separately was 6 and 13 days, respectively. The half-life of fungus formulated in 1% neem was 34 days. Conidia suspended in neem maintained high levels of germination even following a 2-h exposure to ultraviolet radiation. CONCLUSIONS: A combination of the entomopathogenic fungus M. anisopliae with neem oil effectively increases the half-life and virulence of the fungus when tested against Ae. aegypti larvae, even under simulated field conditions. Neem oil also protected the fungus from the damaging effects of ultraviolet radiation.

Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors.

BACKGROUND: Penile carcinoma (PC) is a rare, highly mutilating disease, common in developing countries. The evolution of penile cancer includes at least two independent carcinogenic pathways, related or unrelated to HPV infection. OBJECTIVES: To estimate the prevalence, identify HPV genotypes, and correlate with clinicopathological data on penile cancer. METHODS: A retrospective cohort study involving 183 patients with PC undergoing treatment in a referral hospital in Goiânia, Goiás, in Midwestern Brazil, from 2003 to 2015. Samples containing paraffin embedded tumor fragments were subjected to detection and genotyping by INNO-LiPA HPV. The clinicopathological variables were subjected to analysis with respect to HPV positivity and used prevalence ratio (PR), adjusted prevalence ratio (PRa) and 95% confidence interval (CI) as statistical measures. RESULTS: The prevalence of HPV DNA in PC was 30.6% (95% CI: 24.4 to 37.6), high-risk HPV 24.9% (95% CI: 18.9 to 31.3), and 62.5% were HPV 16. There was a statistical association between the endpoints HPV infection and HPV high risk, and the variable tumor grade II-III (p = 0.025) (p = 0.040), respectively. There was no statistical difference in disease specific survival at 10 years between the HPV positive and negative patients (p = 0.143), and high and low risk HPV (p = 0.325). CONCLUSIONS: The prevalence of HPV infection was 30.6%, and 80.3% of the genotypes were identified as preventable by anti-HPV quadrivalent or nonavalent vaccine. HPV infections and high-risk HPV were not associated with penile carcinoma prognosis in this study.

Improving the delivery and efficiency of fungus-impregnated cloths for control of adult Aedes aegypti using a synthetic attractive lure.

BACKGROUND: Entomopathogenic fungi are highly promising agents for controlling Aedes aegypti mosquitoes. Deploying fungus-impregnated black cloths in PET traps efficiently reduced Ae. aegypti female survival rates under intra-domicile conditions. With the aim of further increasing the effectiveness of the traps, the addition of attractive lures to fungus-impregnated traps was evaluated. METHODS: Black cloths were suspended inside 2 l plastic bottles called "PET traps". These traps were placed in rooms simulating human residences. The first experiments evaluated the attraction of mosquitoes to PET traps with black cloths covered in adhesive film with and without synthetic lures (AtrAedes™). Traps were left in the test rooms for either 24 or 48 h. The attractiveness of the lures over time was also evaluated. The efficiency of PET traps with fungus-impregnated black cloths associated with lures was compared to that of traps without lures. RESULTS: The highest percentage of captured mosquitoes (31 and 66%) were observed in PET traps with black cloths covered in adhesive film + attractive lure maintained in test rooms for 24 h and 48 h, respectively. Black cloths covered in adhesive film captured 17 or 36% of the mosquitoes at 24 h and 48 h, respectively. The attractiveness of the lures fell gradually over time, capturing 37% after 5 days on the bench and 22% of the mosquitoes after 30 days exposure to ambient conditions. Associating attractive synthetic lures with black cloths impregnated with M. anisopliae placed in test rooms for 120 h reduced mean survival to 32%, whilst black cloths impregnated with M. anisopliae without lures resulted in a 48% survival rate. Using Beauveria bassiana in the traps resulted in a 52% reduction in mosquito survival, whilst combining Beauveria and AtrAedes resulted in a 36% survival rate. PET traps impregnated with fungus + AtrAedes resulted in similar reductions in survival when left in the rooms for 24, 48, 72 or 120 h. CONCLUSIONS: AtrAedes increased attractiveness of PET traps with black cloths under intra-domicile conditions and when associated with M. anisopliae or B. bassiana, significantly reduced Aedes survival. This strategy will reduce the number of PET traps necessary per household.

N-acetylcysteine inhibits Mancozeb-induced impairments to the normal development of zebrafish embryos.

Mancozeb (MZ), a manganese/zinc-containing ethylene-bis-dithiocarbamate (EBCD) fungicide has been claimed to present low acute toxicity and short environmental persistence, however, its effects on embryogenesis in non-target organisms is unclear. Here, we used zebrafish embryos (5 hpf) to assess the potential embryotoxic effects induced by MZ (up to 72 hpf) as well as the role of reactive oxygen species (ROS) in this process by pre-treatment with a classical antioxidant (N-acetylcysteine, NAC). Markers of reactive oxygen species production (ROS), glutathione (GSH) levels and glutathione S-transferase (GST) activity were measured along with genotoxicity (comet assay), cell death (Acridine Orange) and behavioral parameters (spontaneous movement, touch stimulation and swimming response), in order to determine potential mechanisms of embryotoxicity. According to results, MZ was able to induce morphological abnormalities such as body axis distortion, DNA damage, cell death, increased ROS generation and changes in behavioral endpoints during zebrafish development. All these toxic effects were inhibited by the pre-treatment with NAC indicating a key role of redox unbalance during MZ-induced embryotoxicity. At least in our knowledge, this is the first report on the deleterious effect of MZ to the normal embryogenesis of zebrafish. In addition, the importance of ROS generation during this pathophysiological condition was highlighted.

Cestrum strigilatum (Ruiz & Pavón, 1799) B chromosome shares repetitive DNA sequences with A chromosomes of different Cestrum (Linnaeus, 1753) species.

Species of Cestrum (Linnaeus, 1753) have shown large diversity in the accumulation and distribution of repetitive DNA families, and B chromosomes have been described in seven species. Some types of repetitive DNA were identified in A and B chromosomes in species of this plant group, such as AT-rich SSR, 35S and 5S rDNA, C-Giemsa and C-CMA/DAPI bands and retrotransposons. To increase our understanding of the relationships of A and B chromosomes, the B of C. strigilatum Ruiz & Pavón, 1799 was microdissected, amplified and hybridized in situ against chromosomes of this species, and in six other species of this genus. FISH signals were observed in whole the B of C. strigilatum, including stretches of A chromosomes, as well as in some A chromosomes of all tested species. A strong FISH signal was seen adjacent to the 5S rDNA in the proximal region of pair 8 of all species and, due to this, we have searched for 5S rDNA fragments in the microdissected B chromosome. PCR and sequencing data evidenced 5S rDNA deletion along evolutionary pathways of the B of C. strigilatum. Although A and B chromosomes displayed redundancy in the repetitive DNA families in different species, the B of C. strigilatum seemed to differ from those Bs of other Cestrum species by the loss of rDNA fractions. A possible origin of Bs in Cestrum was discussed.

Study of association between interleukin-17 and interferon-gamma and recombinant human erythropoietin dose in patients undergoing peritoneal dialysis.

BACKGROUND: A common complication in patients undergoing peritoneal dialysis (PD) is a chronic inflammatory state and anemia that can be treating by recombinant human erythropoietin (rHuEPO). Higher required dose of rHuEPO could be expected in patients with higher cytokine levels. Additionally, it is known that peritoneal inflammation can be correlated with systemic inflammation and this could contribute to the compromised rHuEPO required dose in anemic patients with end stage renal disease (ESRD). Thus, the current study aimed to evaluate the association between levels of systemic and local interferon (IFN)-γ, interleukin (IL)-17 and other cytokines and the dose of rHuEPO used by patients undergoing PD for the correction of anemia. METHODS: Thirty-one patients under PD using rHuEPO were evaluated in this cross-sectional study. Plasma and dialysate levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumour necrosis factor (TNF)-α and IFN-γ were determined using the Cytometric Bead Array TM kit (CBA; BD Bioscences, San Jose, CA). The relation between the levels of each cytokine levels and the tertiles of rHuEPO were plotted on box-plot graphics and then the medians of interleukins levels were compared by median comparison test. The significance level adopted was 5% and the analysis was performed by the softwares STATA (version 12.0) and GraphPad Prism 3.0. RESULTS: The median of IL-17 and IFN-γ plasma levels were significant higher in the group with higher rHuEPO dosage. However, this association was not observed in the dialysate levels, as well as was not observed a relationship between the other plasma and dialysate cytokines evaluated in this study and the dose of rHuEPO. CONCLUSIONS: Our study found increased IL-17 and IFN-γ plasma, but no dialysate levels, in patients receiving higher doses of rHuEPO, suggesting may exist a relationship between systemic inflammation of ESRD, and the necessary levels of rHuEPO for the correction of anemia in these patients.

Does the COPD assessment test reflect functional status in patients with COPD?

The aim of this study was to investigate whether the chronic obstructive pulmonary disease (COPD) assessment test (CAT) reflects the functional status of patients with COPD. Forty-seven patients underwent anthropometric assessment, spirometry, the 6-minute walk test (6MWT), the Glittre-activity of daily living (ADL) test (TGlittre), the London Chest ADL (LCADL) scale, and the CAT. The total score of the CAT correlated with 6MWT distance, TGlittre time spent, and LCADL%total ( r = -0.56, 0.52, and 0.78, respectively; p < 0.05 for all). There was significant difference in 6MWT distance (490 ± 85.4 m vs. 387 ± 56.8 m), TGlittre time spent (3.67 ± 1.07 min vs. 5.03 ± 1.32 min), and LCADL%total (24.2 ± 3.02% vs. 44.4 ± 13.3%) between the low and high impacts of COPD on health status (respectively, p < 0.05 for all) as well as in the LCADL%total between medium and high impact of COPD on health status (31.3 ± 7.35% vs. 44.4 ± 13.3%; p = 0.001). In conclusion, the CAT reflects the functional status of patients with COPD.

Neem oil increases the efficiency of the entomopathogenic fungus Metarhizium anisopliae for the control of Aedes aegypti (Diptera: Culicidae) larvae.

BACKGROUND: Entomopathogenic fungi are potential candidates for use in integrated vector management and many isolates are compatible with synthetic and natural insecticides. Neem oil was tested separately and in combination with the entomopathogenic fungus Metarhizium anisopliae against larvae of the dengue vector Aedes aegypti. Our aim was to increase the effectiveness of the fungus for the control of larval mosquito populations. METHODS: Commercially available neem oil was used at concentrations ranging from 0.0001 to 1%. Larval survival rates were monitored over a 7 day period following exposure to neem. The virulence of the fungus M. anisopliae was confirmed using five conidial concentrations (1 × 10(5) to 1 × 10(9) conidia mL(-1)) and survival monitored over 7 days. Two concentrations of fungal conidia were then tested together with neem (0.001%). Survival curve comparisons were carried out using the Log-rank test and end-point survival rates were compared using one-way ANOVA. RESULTS: 1% neem was toxic to A. aegypti larvae reducing survival to 18% with S50 of 2 days. Neem had no effect on conidial germination or fungal vegetative growth in vitro. Larval survival rates were reduced to 24% (S50 = 3 days) when using 1 × 10(9) conidia mL(-1). Using 1 × 10(8) conidia mL(-1), 30% survival (S50 = 3 days) was observed. We tested a "sub-lethal" neem concentration (0.001%) together with these concentrations of conidia. For combinations of neem + fungus, the survival rates were significantly lower than the survival rates seen for fungus alone or for neem alone. Using a combination of 1 × 10(7) conidia mL(-1) + neem (0.001%), the survival rates were 36%, whereas exposure to the fungus alone resulted in 74% survival and exposure to neem alone resulted in 78% survival. When using 1 × 10(8) conidia mL(-1), the survival curves were modified, with a combination of the fungus + neem resulting in 12% survival, whilst the fungus alone at this concentration also significantly reduced survival rates (28%). CONCLUSIONS: The use of adjuvants is an important strategy for maintaining/increasing fungal virulence and/or shelf-life. The addition of neem to conidial suspensions improved virulence, significantly reducing larval survival times and percentages.

[Pediatric neurofunctional intervention in agenesis of the corpus callosum: a case report]. / Intervenção neurofuncional pediátrica em agenesia do corpo caloso: relato de caso.

OBJECTIVE: To describe a clinical report pre- and post-neurofunctional intervention in a case of agenesis of the corpus callosum. CASE DESCRIPTION: Preterm infant with corpus callosum agenesis and hypoplasia of the cerebellum vermis and lateral ventricles, who, at the age of two years, started the proposed intervention. Functional performance tests were used such as the neurofunctional evaluation, the Gross Motor Function Measure and the Gross Motor Function Classification System. In the initial evaluation, absence of equilibrium reactions, postural transfers, deficits in manual and trunk control were observed. The intervention was conducted with a focus on function, prioritizing postural control and guidance of the family to continue care in the home environment. After the intervention, there was an improvement of body reactions, postural control and movement acquisition of hands and limbs. The intervention also showed improvement in functional performance. COMMENTS: Postural control and transfers of positions were benefited by the neurofunction intervention in this case of agenesis of the corpus callosum. The approach based on function with activities that involve muscle strengthening and balance training reactions, influenced the acquisition of a more selective motor behavior.

Intervenção neurofuncional pediátrica em agenesia do corpo caloso: relato de caso / Pediatric neurofunctional intervention in agenesis of the corpus callosum: a case report

Objetivo: Descrever um relato clínico pré e pós-intervenção neurofuncional num caso de agenesia de corpo caloso. Descrição do caso: Após o nascimento prematuro foi detectada agenesia do corpo caloso e hipoplasia dos ventrículos laterais e vérmis cerebelar. Aos dois anos iniciou a intervenção proposta neste estudo. Uma avaliação neurofuncional, além da Medida da Função Motora Grossa e o Sistema de Classificação da Função Motora Grossa, foi utilizada para obter o desempenho funcional da criança. Na avaliação inicial havia ausência de reações de equilíbrio e de transferências posturais, e déficits no controle manual e de tronco. A intervenção foi realizada com enfoque na função, priorizando o controle postural e a orientação da familia para continuidade do tratamento em ambiente domiciliar. Após a intervenção houve melhora das reações corporais, controle postural e aquisição de movimentos de mãos e membros. A intervenção também mostrou melhora no desempenho funcional. Comentários: O controle postural e as transferências de posições foram beneficiadas por intervenção neurofuncional nesse paciente com agenesia de corpo caloso. O enfoque baseado na função com atividades que envolvem fortalecimento muscular e treinamento das reações de equilíbrio influenciaram a aquisição do comportamento motor mais seletivo...

Objective: To describe a clinical report pre- and post-neurofunctional intervention in a case of agenesis of the corpus callosum. Case description: Preterm infant with corpus callosum agenesis and hypoplasia of the cerebellum vermis and lateral ventricles, who, at the age of two years, started the proposed intervention. Functional performance tests were used such as the neurofunctional evaluation, the Gross Motor Function Measure and the Gross Motor Function Classification System. In the initial evaluation, absence of equilibrium reactions, postural transfers, deficits in manual and trunk control were observed. The intervention was conducted with a focus on function, prioritizing postural control and guidance of the family to continue care in the home environment. After the intervention, there was an improvement of body reactions, postural control and movement acquisition of hands and limbs. The intervention also showed improvement in functional performance. Comments: Postural control and transfers of positions were benefited by the neurofunction intervention in this case of agenesis of the corpus callosum. The approach based on function with activities that involve muscle strengthening and balance reactions training, influenced the acquisition of a more selective motor behavior...

Monitoring persistence of the entomopathogenic fungus Metarhizium anisopliae under simulated field conditions with the aim of controlling adult Aedes aegypti (Diptera: Culicidae).

BACKGROUND: Entomopathogenic fungi are potential candidates for use in integrated vector management, with recent emphasis aimed at developing adult mosquito control methods. Here we investigated the persistence of the fungus Metarhizium anisopliae when tested against female A. aegypti under field conditions. METHODS: Black cotton cloths impregnated with M. anisopliae conidia, formulated in vegetable oil + isoparaffin, were maintained on a covered veranda for up to 30 days. At specific times, pieces of the cloths were removed, placed in Tween 80 and the resuspended conidia were sprayed directly onto mosquitoes. The persistence of conidia impregnated on black cloths using three different carriers was evaluated in test rooms. Fifty mosquitoes were released into each room and after a 5 day period, the surviving insects were captured. Another 50 insects were then released into each room. The capacity of the fungus at reducing mosquito survival was evaluated over a total of 35 days. RESULTS: Conidia extracted from cloths maintained on the veranda for 2 to 18 days remained virulent, with 28 to 60% mosquito survival observed. Mosquito survival following exposure to fungus impregnated cloths showed that fungus + Tween caused similar reductions to that of fungus + vegetable oil. Mosquitoes exposed to the formulation fungus + vegetable oil had survival rates of 36% over the first 5 days of the experiment. Following the release of the second cohort of mosquitoes (6-11days), survival increased to 50%. The survival of the 12-17 day cohort (78%) was statistically equal to that of the controls (84%). Formulation of the fungus in vegetable oil + isoparaffin increased the persistence of the fungus, with the 18-23 day cohort (64% survival) still showing statistical differences to that of the controls (87% survival). CONCLUSIONS: The potential of entomopathogenic fungi for the control of adult A. aegypti was confirmed under field conditions. Vegetable oil + isoparaffin formulations of M. anisopliae significantly increased the effectiveness of the fungus, thus reducing the need for frequent changes of black cloths in residences. Our future aim is to obtain effective control of mosquito populations, with cloths only needing to being replaced once a month.

Testing fungus impregnated cloths for the control of adult Aedes aegypti under natural conditions.

BACKGROUND: Entomopathogenic fungi could be useful tools for reducing populations of the dengue mosquito Aedes aegypti. Here the efficiency of fungus (Metarhizium anisopliae) impregnated cloths (with and without imidacloprid [IMI]) was evaluated against adult A. aegypti in simulated human dwellings. Behaviour of mosquitoes in the presence of black cloths was also investigated. FINDINGS: When mosquitoes were released into the test rooms, the lowest survival rates (38%) were seen when five black cloths impregnated with conidia of ESALQ 818 + 10 ppm IMI were fixed under tables and chairs. This result was significantly lower than the survival rate recorded when cloths were impregnated with ESALQ 818 alone (44%) or ESALQ 818 + 0.1 ppm IMI (43%). Blood fed A. aegypti had lower landing frequencies on black cloths than sucrose fed insects during the first 24 h following feeding, which may have been due to reduced flight activity. Few mosquitoes (4-5%) were observed to land on the cloths during the hours of darkness. The landing pattern of sucrose-fed mosquitoes on non-treated and fungus-treated cloths was similar. CONCLUSION: The synergism between M. anisopliae and IMI significantly reduced Aedes survival in simulated field conditions. The use of fungus impregnated cloths is a promising point source application method for the control of adult A. aegypti.