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Rodrigo A Brant Fernandes,1 Luci Meire P Silva,1 Diego Torres Dias,1 Rafael Henrique Pereira,2 Rubens Belfort Jr,1,2 Tiago Santos Prata1–31Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, São Paulo, SP, Brazil; 2IPEPO/Vision Institute – SP, São Paulo, SP, Brazil; 3Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USAPurpose: To evaluate the therapeutic non-inferiority between two ophthalmic latanoprost 0.005% solutions (Arulatan®, [ALT] versus the reference drug Xalatan®, [XLT]) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).Patients and methods: This was a 12-week Phase IV, experimental, randomized, parallel-group, double-masked clinical trial. Consecutive patients with POAG or OH from the Glaucoma Service of Instituto Paulista de Estudos e Pesquisas em Oftalmologia (São Paulo, Brazil) were enrolled between July and December 2017. The primary outcome of the study was an analysis of therapeutic non-inferiority between ALT versus XLT at 12 weeks, while secondary outcomes were mean intraocular pressure (IOP) change from baseline at 2, 6 and 12 weeks, mean IOP at 2, 6 and 12 weeks, and topical and systemic side effects. Statistical significance was set at P

Culex quinquefasciatus is a mosquito species with an anthropophilic habit, often associated with areas with poor sanitation in tropical and urban regions. Adult males and females feed on sugars but only females feed on blood in natural conditions for egg maturation. During haematophagy, female C. quinquefasciatus transmit pathogens such as the West Nile virus, Oropouche virus, various encephalitis viruses, and Wuchereria bancrofti to human hosts. It has been observed in laboratory conditions that male C. quinquefasciatus may feed on blood during an artificial feed. Experiments were carried out to understand how males and females of this species deal with human complement activation. Our results showed that female C. quinquefasciatus, but not males, withstand the stress caused by the ingestion of normal human serum. It was observed that the salivary gland extracts from female mosquitoes were able to inhibit the classical and lectin pathways, whereas male salivary gland extracts only inhibited the lectin pathway. The male and female intestinal contents inhibited the classical and lectin pathways. Neither the salivary glands nor the intestinal contents from males and females showed inhibitory activity towards the alternative pathway. However, the guts of male and female C. quinquefasciatus captured factor H from the human serum, permitting C3b inactivation to its inactive form iC3b, and preventing the formation of the C3 convertase. The activity of the antioxidant enzyme catalase is similar in C. quinquefasciatus females and males. This article shows for the first time that males from a haematophagous arthropod species present human anti-complement activity in their salivary gland extracts and gut contents. The finding of an activity that helps to protect the damage caused by blood ingestion in sugar-feeding male mosquitoes suggests that this may be a pre-adaptation to blood-feeding., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We herein present a Brazilian guideline for the management of feline sporotrichosis, a mycosis caused by Sporothrix brasiliensis. This guideline is an effort of a national technical group organized by the Working Group on Sporothrix and Sporotrichosis of the International Society for Human and Animal Mycology (ISHAM). This publication intends to provide information on clinical-epidemiological aspects of this zoonosis, as well as a literature revision. Moreover, it gives some practical information on diagnosis and treatment of feline sporotrichosis. It also contains information that can be helpful for the prevention and control of S. brasiliensis transmission.

Aedes aegypti is the main urban vector of dengue virus, chikungunya virus and Zika virus due to its great dispersal capacity and virus susceptibility. A. aegypti feed on plant-derived sugars but females need a blood meal for egg maturation. Haematophagous arthropods need to overcome host haemostasis and local immune reactions in order to take a blood meal. In this context, molecules present in the saliva and/or intestinal contents of these arthropods must contain inhibitors of the complement system (CS). CS salivary and/or intestinal inhibitors are crucial to protect gut cells of haematophagous arthropods against complement attack. The present work aimed to investigate the anti-complement activity of A. aegypti intestinal contents on the alternative, classical and lectin pathways of the human complement system. Here we show that A. aegypti gut contents inhibited the human classical and the lectin pathways but not the alternative pathway. The A. aegypti gut content has a serine protease able to specifically cleave and inactivate human C4, which is a novel mechanism for human complement inactivation in haematophagous arthropods. The gut of female A. aegypti was capable of capturing human serum factor H (a negative complement modulator), unlike males. C3 molecules in recently blood-fed female A. aegypti remain in their original state, being inactivated to iC3b soon after a blood feed. A transmission-blocking vaccine using these complement inhibitory proteins as antigens has the potential to interfere with the insect's survival, reproductive fitness and block their infection by the arboviruses they transmit to humans., Competing Interests: Declaration of competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the therapeutic non-inferiority between two ophthalmic latanoprost 0.005% solutions (Arulatan ® [ALT] versus the reference drug Xalatan ® [XLT]) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Patients and methods: This was a 12-week Phase IV, experimental, randomized, parallel-group, double-masked clinical trial. Consecutive patients with POAG or OH from the Glaucoma Service of Instituto Paulista de Estudos e Pesquisas em Oftalmologia (São Paulo, Brazil) were enrolled between July and December 2017. The primary outcome of the study was an analysis of therapeutic non-inferiority between ALT versus XLT at 12 weeks, while secondary outcomes were mean intraocular pressure (IOP) change from baseline at 2, 6 and 12 weeks, mean IOP at 2, 6 and 12 weeks, and topical and systemic side effects. Statistical significance was set at P <0.05. Computerized analysis was performed using the R software, version 3.4.4. Results: A total of 45 patients were randomized to the two treatment groups: ALT (22) and XLT (23). A statistically significant reduction in IOP from baseline was observed in both treatment groups at all timepoints, while no statistically significant difference between groups was detected. By week 12, observed IOP reduction was -7.95 and -7.89 mmHg in the ALT and in the XLT groups, respectively ( P =0.60). Treatment difference between the ALT and the XLT groups was -0.06 mm Hg (95% CI: -0.97, 0.85) and fell within the interval set for therapeutic non-inferiority. There was no statistically significant difference between the two groups in terms of safety profiles. The most commonly reported side effect was mild conjunctival/palpebral hyperemia. Conclusion: ALT was considered non-inferior to XLT in achieving a statistically significant reduction in IOP at 12 weeks in POAG and OH patients. No significant difference in the occurrence of side effects was found between both groups., Competing Interests: Diego Torres Dias, Rubens Belfort Jr, and Tiago Santos Prata report grants from Bausch & Lomb, during the conduct of the study. The authors report no proprietary interest and no other conflicts of interest in this work.

Paracoccidioidomycosis (PCM) is a systemic mycosis with lymphatic dissemination that is caused by Paracoccidioides species. Treatment of PCM consists of chemotherapeutics such as itraconazole, trimethoprim, sulfamethoxazole or amphotericin B. However, several studies are aiming to develop therapeutic alternatives for the treatment of fungal infection using new molecules as adjuvants. The single-chain variable fragments (scFv) from an antibody that mimics the main fungal component incorporated within poly(lactide-co-glycolic) acid (PLGA) nanoparticles helped treat the fungal disease. After expressing the scFv in Picchia pastoris (P. pastoris), the recombinant molecules were coupled with PLGA, and the BALB/c mice were immunized before or after infection with yeast Paracoccidioides brasiliensis (P. brasiliensis). Our results showed decreased disease progression and decreased fungal burden. Taken together, our results showed an increased of IFN-γ and IL-12 cytokine production and an increased number of macrophages and dendritic cells in the pulmonary tissue of BALB/c mice treated with a high concentration of our molecule. Our data further confirm that the scFv plays an important role in the treatment of experimental PCM., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Achromobacter spp. are opportunistic pathogens increasingly recovered from adult patients with cystic fibrosis (CF). We report the characterization of 122 Achromobacter spp. isolates recovered from 39 CF patients by multilocus sequence typing, virulence traits, and susceptibility to antimicrobials. Two species, A. xylosoxidans (77%) and A. ruhlandii (23%) were identified. All isolates showed a similar biofilm formation ability, and a positive swimming phenotype. By contrast, 4·3% and 44·4% of A. xylosoxidans and A. ruhlandii, respectively, exhibited a negative swarming phenotype, making the swimming and swarming abilities of A. xylosoxidans significantly higher than those of A. ruhlandii. A. xylosoxidans isolates from an outbreak clone also exhibited significantly higher motility. Both species were generally susceptible to ceftazidime, ciprofloxacin, imipenem and trimethoprim/sulphamethoxazole and there was no significant difference in susceptibility between isolates from chronic or sporadic infection. However, A. xylosoxidans isolates from chronic and sporadic cases were significantly more resistant to imipenem and ceftazidime than isolates of the outbreak clone.

Objective: To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions., Methods: By using data from the Health section of 2008's Pesquisa Nacional por Amostra de Domicílio (Brazil's National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country., Results: A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals., Conclusions: Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making., Objetivo: Apresentar estimativas nacionais sobre o deslocamento a pé ou de bicicleta no trajeto casa-trabalho no Brasil e em 10 de suas regiões metropolitanas., Métodos: Utilizando dados do Suplemento sobre Saúde da Pesquisa Nacional por Amostra de Domicílios de 2008, estimamos a frequência de pessoas empregadas que se deslocam a pé ou de bicicleta no trajeto casa-trabalho estratificada por sexo, e segundo faixa etária, escolaridade, renda domiciliar per capita, residência em área urbana ou rural, regiões metropolitanas e macrorregiões do país. Adicionalmente, estimamos a distribuição da mesma frequência segundo quintos da distribuição da renda domiciliar per capita em cada região metropolitana., Resultados: Um terço dos homens e mulheres empregados desloca-se a pé ou de bicicleta de casa para o trabalho no Brasil. Em ambos os sexos, esta proporção diminui com o aumento da renda e da escolaridade e é maior entre os mais jovens, entre os que residem em área rural e naqueles residentes na região Nordeste. A depender da região metropolitana, a prática de deslocamento ativo entre os mais pobres é de duas a cinco vezes maior do que entre os mais ricos., Conclusões: O deslocamento a pé ou de bicicleta para o trabalho no Brasil é mais frequente entre os mais pobres e entre pessoas que vivem em áreas e regiões economicamente menos desenvolvidas. A avaliação do deslocamento ativo no País traz informações importantes para a discussão de políticas públicas de mobilidade.

This study aims to estimate mortality differentials by level of schooling in the adult population in Brazil as a whole and its major geographic regions, according to sex and age. The article uses data from the item on household mortality in the 2010 Population Census conducted by Brazilian Institute of Geography and Statistics, combined with information on schooling of the household's reference person. The results show an important mortality differential by level of schooling, especially in males. Life expectancy in Brazilian men with a complete university education is 4.37 years more than the mean for the national male population and 6.27 years more than for males with less than a complete primary education. Among women, the educational gradient in life expectancy is less pronounced, with an additional 2.25 years for women with a complete university education, compared to women with less schooling. Mortality differentials according to schooling are more pronounced in the Northeast and Southeast regions.

The rate of diagnosis of colonization/infection of the airways with Achromobacter xylosoxidans has increased in cystic fibrosis patients, but its clinical significance is still controversial. This retrospective, case-control study aimed to evaluate the clinical impact of A. xylosoxidans colonization/infection in cystic fibrosis patients. Individuals who were chronically colonized/infected (n=10), intermittently colonized/infected (n=15), and never colonized/infected with A. xylosoxidans (n=18) were retrospectively evaluated during two periods that were 2 years apart. Demographic characteristics, clinical data, lung function, and chronic bacterial co-colonization data were evaluated. Of the total study population, 87% were pediatric patients and 65.1% were female. Individuals chronically colonized/infected with A. xylosoxidans had decreased forced expiratory volume in 1 s (51.7% in the chronic colonization/infection group vs 82.7% in the intermittent colonization/infection group vs 76% in the never colonized/infected group). Compared with the other two groups, the rate of co-colonization with methicillin-resistant Staphylococcus aureus was higher in individuals chronically colonized/infected with A. xylosoxidans (P=0.002). Changes in lung function over 2 years in the three groups were not significant, although a trend toward a greater decrease in lung function was observed in the chronically colonized/infected group. Compared with the other two groups, there was a greater number of annual hospitalizations in patients chronically colonized/infected with A. xylosoxidans (P=0.033). In cystic fibrosis patients, there was an increased frequency of A. xylosoxidans colonization/infection in children, and lung function was reduced in patients who were chronically colonized/infected with A. xylosoxidans. Additionally, there were no differences in clinical outcomes during the 2-year period, except for an increased number of hospitalizations in patients with A. xylosoxidans.

Purpose: To evaluate the effectiveness of topical 1% cyclosporine eye drops diluted in either of the two vehicles-olive and linseed oil-and that of the oils themselves in treating experimentally-induced keratoconjunctivitis sicca (KCS) in rabbits., Methods: KCS was induced in 25 New Zealand rabbits using 1% atropine sulfate eye drops for 7 days before treatment and throughout the treatment period (12 weeks). The rabbits were divided into five groups: one control (C) group without KCS induction and four treatment groups in which KCS was induced and treated topically with olive oil (O), linseed oil (L), cyclosporine in olive oil (CO), and cyclosporine in linseed oil (CL). The animals were evaluated using Schirmer tear test 1 (STT), the fluorescein test (FT), tear-film break-up time (TBUT), the rose bengal test (RBT), and histopathological analysis., Results: Values of STT and TBUT significantly decreased 1 week post-induction (p<0.05) and were similar to initial values after the 4th week of treatment, in all groups. After KCS induction, there was significantly less corneal damage in group L than in group CL, as assessed FT and RBT. Histopathology demonstrated that Groups L and CL presented less edema and corneal congestion. There was no significant difference in the goblet cell density (cells/mm2) between the groups (p=0.147)., Conclusion: Cyclosporine diluted in olive oil or linseed oil was effective in the treatment of KCS, although it had better efficacy when diluted in linseed oil. Linseed oil presented better effectiveness, whether associated or not, than olive oil. These results may contribute to the creation of novel topical ophthalmic formulations for KCS treatment in future.

The giant earthworm, Rhinodrilus alatus (Righi 1971), has been captured in the southeastern Brazilian Cerrado biome for approximately 80 years and used as bait for amateur fishing throughout Brazil. Local knowledge and traditional extraction practices are crucial for the establishment of management strategies for the species because, although its extraction involves conflicts and social and environmental impacts, the species is one of the major sources of income for approximately 3,000 people, especially for members of an Afro-descendant community that has approximately 2,000 inhabitants. Participatory tools, such as seasonal calendar, transect walks and participatory maps, were individually or collectively used with extractors and traders (former extractors), and 129 semi-structured and unstructured interviews were conducted with the same individuals between 2005 and 2012. The capture of Rhinodrilus alatus was observed in different seasons and areas of occurrence of the species in 17 municipalities, where this giant earthworm is the only species extracted for trade. All information obtained was verified by community members in 17 meetings. The extractors have an extensive knowledge of the life history, behavior, distribution, and possible impacts of climate change on the species. Different capture techniques, which have different impacts, are used during the dry and rainy seasons and are passed by the extractors through the generations. Local knowledge contributed to the establishment of agreements for the use of capture techniques that have less impact, to the expansion of scientific knowledge and the reassessment of the conservation status of Rhinodrilus alatus. The present study may serve as an example for management projects for other giant earthworm species in other regions of Brazil and in other countries.

VML is a lectin from Vatairea macrocarpa seeds that has various biological activities. Here, we describe three new lectin isoforms from V. macrocarpa identified through genomic DNA analysis. One of these isoforms has high similarity to VML, while another that has noteworthy differences. We have denoted the new isoforms as VML-2, VML-3 and VML-4. Recombinant VML (rVML) and VML-2 (rVML-2) were expressed in Escherichia coli and were anticipated to have similar biological activity compared to native VML. Recombinant lectins were produced using a synthetic gene strategy to improve the expression levels. We obtained two active recombinant lectin isoforms from V. macrocarpa, and there was no significant difference between their biological activities. The conservation between carbohydrate-binding sites of recombinant and native proteins was demonstrated by specific inhibition of hemagglutin activity by D-galactose and lactose. However, no inhibition was observed in the presence of glucose and mannose. Our data show that the recombinant lectins VML and VML-2 are active and capable of recognising D-galactose and lactose. Moreover, the absence of glycosylation does not interfere with their biological activity.

We evaluated the performance of matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) for identification of Bcc species compared with that of recA sequencing. MALDI-ToF was able of identifying 100% of Bcc isolates at the genus level, but 23.1% of Bcc isolates tested were not correctly identified at the species level. The misidentification occurred most frequently with Burkholderia contaminans (100%) and B. cepacia (33.3%)., (© 2013 Elsevier Inc. All rights reserved.)

We investigated the possibility of cross-infection among cystic fibrosis patients in two Brazilian reference centers. Achromobacter xylosoxidans isolates (n = 122) were recovered over a 5-year period from 39 patients. Isolates were genetically heterogeneous, but one genotype was present in 56% of the patients, suggesting that cross-infection may have occurred.

Bacteria producing Klebsiella pneumoniae carbapenemases (KPCs) are rapidly emerging as a cause of multidrug-resistant infections worldwide. KPCs enzyme are plasmid-borne and can accumulate and transfer resistance determinants to other classes of antibiotics.We report two cases of KPC-2 carbapenemase-producing Klebsiella pneumoniae isolates from Cystic Fibrosis patients., (Copyright © 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

The control of Visceral Leishmaniasis (VL) vector is often based on the application of chemical residual insecticide. However, this strategy has not been effective. The continuing search for an appropriate vector control may include the use of biological control. This study evaluates the effects of the fungus Metarhizium anisopliae var. acridum on Lutzomyia longipalpis. Five concentrations of the fungus were utilized, 1 x 10(4) to 1 x 10(8) conidia/ml, accompanied by controls. The unhatched eggs, larvae and dead adults previously exposed to fungi were sown to reisolate the fungi and analysis of parameters of growth. The fungus was subsequently identified by PCR and DNA sequencing. M. anisopliae var. acridum reduced egg hatching by 40%. The mortality of infected larvae was significant. The longevity of infected adults was lower than that of negative controls. The effects of fungal infection on the hatching of eggs laid by infected females were also significant. With respect to fungal growth parameters post-infection, only vegetative growth was not significantly higher than that of the fungi before infection. The revalidation of the identification of the reisolated fungus was confirmed post-passage only from adult insects. In terms of larvae mortality and the fecundity of infected females, the results were significant, proving that the main vector species of VL is susceptible to infection by this entomopathogenic fungus in the adult stage., (Copyright 2009 Elsevier B.V. All rights reserved.)

We describe the recovery of Paenibacillus cineris from a Brazilian cystic fibrosis (CF) patient. Paenibacillus spp. are mainly environmental organisms. Although the role that these species play in lung disease is not known, we highlight the importance of careful attention to unusual bacteria from respiratory secretions of CF patients.

An evaluation was made of the quality of samples of water and sediment collected from a series of reservoirs in the Tietê River (SP), based on limnological and ecotoxicological analyses. The samples were collected during two periods (Feb and Jul 2000) from 15 sampling stations. Acute toxicity bioassays were performed using the test organism Daphnia similis, while chronic bioassays were carried out with Ceriodaphnia dubia and Danio rerio larvae. The water samples were analyzed for total nutrients, total suspended matter and total cadmium, chromium, copper and zinc concentrations, while the sediment samples were examined for organic matter, granulometry and potentially bioavailable metals (cadmium, chromium, copper and zinc). The results obtained for the limnological variable, revealed differences in the water quality, with high contribution of nutrients and metals for Tietê and Piracicaba rivers, besides the incorporation and sedimentation, consequently causing a reduction of materials in Barra Bonita reservoir, thus promoting the improvement of the water quality in the other reservoirs. The toxicity bioassays revealed acute toxicity for Daphnia similis only in the reservoirs located below Barra Bonita dam. On the other hand, chronic toxicity for Ceriodaphnia dubia and acute for Danio rerio showed a different pattern, decreasing in magnitude from Barra Bonita to Três Irmãos, demonstrating an environmental degradation gradient in the reservoirs.