Effect of fluralaner on the biology, survival, and reproductive fitness of the neotropical malaria vector Anopheles aquasalis.

BACKGROUND: Reducing mosquito abundance or interfering with its ability to support the parasite cycle can help to interrupt malaria in areas of significant risk of malaria transmission. Fluralaner is a safe and effective drug for veterinary use indicated for the treatment against fleas and ticks which acts as an antagonist of chloride ion channels mediated by γ-aminobutyric acid (GABA), preventing the entry of these ions into the postsynaptic neuron, leading to hyperexcitability of the postsynaptic neuron of the central nervous system of arthropods. Fluralaner demonstrated insecticidal activity against different insect species. METHODS: The study aimed to evaluate the effects of fluralaner on the biology, survival, and reproductive fitness of Anopheles aquasalis. The following lethal concentrations (LC) were determined for An. aquasalis: LC5 = 0.511 µM; LC25 = 1.625 µM; LC50 = 3.237 µM. RESULTS: A significant decrease (P < 0.001) was evident in the number of eggs, larvae, and pupae in the group exposed to a sublethal dose of fluralaner when compared to a control group (without the drug). Using blood from dogs after administration of fluralaner, it was observed that the drug causes 100% mortality in An. aquasalis in less than 24 h after feeding; this effect remains even after 90 days in all samples. DISCUSSION: Fluralaner showed the same result for up to 60 days, and after that, there was a slight reduction in its effect, evidenced by a decrease in the percentage of dead females; however, still significant when compared to the control group. CONCLUSION: Fluralaner affects the biology and reduction of survival in An. aquasalis in a lasting and prolonged period, and its fecundity with lower dosages, is a strong candidate for controlling disease vectors.

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated. Pellets were prepared via extrusion-spheronization and coated using two acrylic polymers (Eudragit® FS 30 D and Opadry® 94 k28327, PMMA and PMA, respectively). The resulting pellets were mixed with placebo granules and compressed in a hydraulic press. Multiple regression showed that ketoprofen release from pellet-containing tablets is predominantly influenced by pellet content, hardness, friability, and disintegration time. PMA-containing tablets prepared under low compaction force or with low pellet content showed rapid disintegration (<1 min) and ketoprofen release similar to those of uncompressed coated pellets (∼30% at 360 min of experiment). On the other hand, PMMA-containing tablets showed a higher rupture level, and those prepared with higher pellet content gave rise to a non-disintegrating matrix. Coated pellets were shown to be able to target ketoprofen to the colonic region. Targeting capacity was dependent on the physicochemical characteristics of the tablets.

Preliminary profile of the gut microbiota from amerindians in the Brazilian amazon experiencing a process of transition to urbanization.

The Yanomami are one of the oldest indigenous tribes in the Amazon and are direct descendants of the first people to colonize South America 12,000 years ago. They are located on the border between Venezuela and Brazil, with the Venezuelan side remaining uncontacted. While they maintain a hunter-gatherer society, they are currently experiencing contact with urbanized populations in Brazil. The human gut microbiota of traditional communities has become the subject of recent studies due to the Westernization of their diet and the introduction of antibiotics and other chemicals, which have affected microbial diversity in indigenous populations, thereby threatening their existence. In this study, we preliminarily characterized the diversity of the gut microbiota of the Yanomami, a hunter-gatherer society from the Amazon, experiencing contact with urbanized populations. Similarly, we compared their diversity with the population in Manaus, Amazonas. A metabarcoding approach of the 16 S rRNA gene was carried out on fecal samples. Differences were found between the two populations, particularly regarding the abundance of genera (e.g., Prevotella and Bacteroides) and the higher values of the phyla Bacteroidetes over Firmicutes, which were significant only in the Yanomami. Some bacteria were found exclusively in the Yanomami (Treponema and Succinivibrio). However, diversity was statistically equal between them. In conclusion, the composition of the Yanomami gut microbiota still maintains the profile characteristic of a community with a traditional lifestyle. However, our results suggest an underlying Westernization process of the Yanomami microbiota when compared with that of Manaus, which must be carefully monitored by authorities, as the loss of diversity can be a sign of growing danger to the health of the Yanomami.

Unravelling the genome of the brackish water malaria vector Anopheles aquasalis.

Malaria is a severe public health problem in several developing tropical and subtropical countries. Anopheles aquasalis is the primary coastal malaria vector in Central and South America and the Caribbean Islands, and it has the peculiar feature of living in water with large changes in salinity. Recent research has recognised An. aquasalis as an important model for studying the interactions of murine and human Plasmodium parasites. This study presents the complete genome of An. aquasalis and offers insights into its evolution and physiology. The genome is similar in size and gene content to other Neotropical anophelines, with 162 Mb and 12,446 protein-coding genes. There are 1387 single-copy orthologs at the Diptera level (eg. An. gambiae, An. darlingi and Drosophila melanogaster). An. aquasalis diverged from An. darlingi, the primary malaria vector in inland South America, nearly 20 million years ago. Proteins related to ion transport and metabolism belong to the most abundant gene families with 660 genes. We identified gene families relevant to osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases, and carbonic anhydrases). Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in insecticide resistance and immunity-related genes for all known classical pathways. The data provided by this study offers candidate genes for further studies of parasite-vector interactions and for studies on how anophelines of brackish water deal with the high fluctuation in water salinity. We also established data and insights supporting An. aquasalis as an emerging Neotropical malaria vector model for genetic and molecular studies.

Vector Competence for Zika Virus Changes Depending on the Aedes aegypti's Region of Origin in Manaus: A Study of an Endemic Brazilian Amazonian City.

Zika virus (ZIKV) is transmitted to humans by the infectious bite of mosquitoes such as Aedes aegypti. In a city, the population control of mosquitoes is carried out according to alerts generated by different districts via the analysis of the mosquito index. However, we do not know whether, besides mosquito abundance, the susceptibility of mosquitoes could also diverge among districts and thus impact the dissemination and transmission of arboviruses. After a viremic blood meal, the virus must infect the midgut, disseminate to tissues, and reach the salivary gland to be transmitted to a vertebrate host. This study evaluated the patterns of ZIKV infection in the Ae. aegypti field populations of a city. The disseminated infection rate, viral transmission rate, and transmission efficiency were measured using quantitative PCR at 14 days post-infection. The results showed that all Ae. aegypti populations had individuals susceptible to ZIKV infection and able to transmit the virus. The infection parameters showed that the geographical area of origin of the Ae. aegypti influences its vector competence for ZIKV transmission.

Evolution and assembly of Anopheles aquasalis's immune genes: primary malaria vector of coastal Central and South America and the Caribbean Islands.

Anophelines are vectors of malaria, the deadliest disease worldwide transmitted by mosquitoes. The availability of genomic data from various Anopheles species allowed evolutionary comparisons of the immune response genes in search of alternative vector control of the malarial parasites. Now, with the Anopheles aquasalis genome, it was possible to obtain more information about the evolution of the immune response genes. Anopheles aquasalis has 278 immune genes in 24 families or groups. Comparatively, the American anophelines possess fewer genes than Anopheles gambiae s. s., the most dangerous African vector. The most remarkable differences were found in the pathogen recognition and modulation families like FREPs, CLIP and C-type lectins. Even so, genes related to the modulation of the expression of effectors in response to pathogens and gene families that control the production of reactive oxygen species were more conserved. Overall, the results show a variable pattern of evolution in the immune response genes in the anopheline species. Environmental factors, such as exposure to different pathogens and differences in the microbiota composition, could shape the expression of this group of genes. The results presented here will contribute to a better knowledge of the Neotropical vector and open opportunities for malaria control in the endemic-affected areas of the New World.

Acute kidney injury and other factors associated with mortality in hiv-infected patients.

OBJECTIVE: HIV-related mortality is still high, especially in developed countries. The aim of this study is to investigate factors associated to death in HIV-infected patients. METHODS: This is a cross-sectional study with all HIV adult patients admitted to a tertiary infectious diseases hospital in Fortaleza, Northeast Brazil, from January 2013 to December 2014. Patients were divided into two groups: survivors and non-survivors. Demo-graphical, clinical and laboratory data were compared and a logistic regression was performed in order to investigate risk factors for death. P values ≤0.05 were considered statistically significant. RESULTS: A total of 200 patients with mean age of 39 years were including in the study, 69.5% males. Fifteen patients (7.5%) died. Non-survivors presented a higher percentage of males (93.3 vs. 67.3%, p = 0.037). Non-survivors presented AKI (73.3 vs. 10.3%, p < 0.001), liver dysfunction (33.3 vs. 11.5, p = 0.031), dyspnea (73.3 vs. 33.0%, p = 0.002) and disorientation (33.3 vs. 12.4%, p = 0.025) more frequently. Non-survivors also had higher levels of urea (73.8 ± 52.7vs. 36.1 ± 29.1 mg/dL, p < 0.001), creatinine (1.98 ± 1.65 vs. 1.05 ± 1.07 mg/dL, p < 0.001), aspartate aminotransferase (130.8 vs. 84.8 U/L, p = 0.03), alanine aminotransferase (115.6 vs. 85.4 U/L, p = 0.045) and lactate dehydrogenase (LDH) (1208 vs. 608 U/L, p = 0.012), as well as lower levels of bicarbonate (18.0 ± 4.7 vs. 21.6 ± 4.6 mEq/L, p = 0.016) and PCO2 (27.8 ± 7.7 vs. 33.0 ± 9.3 mmHg, p = 0.05). In multivariate analysis, disorientation (p = 0.035, OR = 5.523, 95%CI = 1.130 - 26.998), dyspnoea (p = 0.046, OR = 4.064, 95%CI = 1.028 - 16.073), AKI (p < 0.001, OR = 18.045, 95%CI = 4.308 - 75.596) and disseminated histoplasmosis (p = 0.016, OR = 12.696, 95%CI = 1.618 - 99.646) and LDH > 1000 U/L (p = 0.038, OR = 4.854, 95%CI = 1.093 - 21.739) were risk factors for death.]CONCLUSION: AKI and disseminated histoplasmosis (DH) were the main risk factors for death in the studied population. Neurologic and respiratory impairment as well as higher levels of LDH also increased mortality in HIV-infected patients.

Desilusão: Impasses Clínicos e Políticos diante dos Dilemas de nosso Tempo / Disillusionment: Clinical and Political Impasses in the Face of the Dilemmas of our Time / Desilusión: Problemáticas Clínicas y Políticas ante los Dilemas de nuestro Tiempo / Déception: Des Impasses Cliniques et Politiques Face aux Dilemmes de notre Époque

Acontecimentos sociais e políticos, nacionais e internacionais, têm abalado nosso cotidiano. Conquistas que pareciam sedimentadas na direção da democracia e nos temas relativos aos direitos humanos, conquistas sociais e considerações éticas na vida política, têm sido substituídas por chavões e discursos de ódio, racismo e xenofobia sob a lógica da guerra. Desse modo, têm sido enfrentados fluxos massivos de imigrantes, frutos de guerras e violências, atentados terroristas e uma tensão cotidiana em que o debate localiza no outro o perigo: generaliza-se a figura do terrorista. Vamos propor um deslocamento da lógica da guerra a fim de dialogar sobre a queda dos ideais e das ilusões e as dificuldades de traçar direções para o futuro. Vamos apontar o imbricado enlace entre ética do desejo, política e resistência à instrumentação social do gozo. Entendemos que perder um ideal é diferente de perder uma ilusão, crença ou delírio. A descrença, a desilusão, tem seus efeitos ­ um deles é agarrar-se à fantasia delirante. A idealização é um processo que envolve o engrandecimento e superestimação do objeto, não dizendo respeito ao ideal. A aflição psíquica nomeada "desilusão" estende-se dos ideais culturais (no plano do ideal-do-Eu) às expectativas do Eu (plano do Eu-ideal). Essa questão nos alerta para o encobrimento de outra ilusão, de autoengendramento, de poder superar a dependência simbólica ao Outro. Diferenciar esses termos nos permite apontar o imbricado enlace entre ética do desejo, política e a resistência à instrumentação social do gozo. Quanto à posição da psicanálise, retomaremos a frase de Lacan em Ciência e Verdade (1966/1998): "Por nossa posição de sujeito somos sempre responsáveis. Que chamem a isto como quiserem, terrorismo".

Social and political events, national and international, have shaken our daily lives. Conquests that seemed to be set in the direction of democracy and on issues related to human rights, social achievements and ethical considerations in political life have been replaced by slogans and discourses of hatred, racism and xenophobia under the logic of war. In this way, massive flows of immigrants, fruits of wars and violence, terrorist attacks and a daily tension have been faced in which the debate finds in the other the danger: generalizes the figure of the terrorist. Let us propose a shift in the logic of war in order to talk about the fall of ideals and illusions and the difficulties of drawing directions for the future. Let us point to the overlapping link between ethics of desire, politics, and resistance to the social instrumentation of enjoyment. We understand that losing an ideal is different from losing an illusion, belief or delusion. Disbelief, disillusionment, has its effects - one of them is clinging to delusional fantasy. Idealization is a process that involves the enhancement and overestimation of the object, not referring to the ideal. The psychic affliction named "disillusionment" extends from cultural ideals (on the plane of the egoideal) to the expectations of the Self (plane of the I-ideal). This question alerts us to the cover-up of another illusion, of self-surrender, of being able to overcome symbolic dependence on the Other. Differentiating these terms allows us to point out the imbricated link between ethics of desire, politics and resistance to the social instrumentation of joy. Regarding the position of psychoanalysis, we shall return to Lacan's phrase in Science and Truth (1966/1998): "By our position of subject we are always responsible. Call it this way, terrorism".

Acontecimientos sociales y políticos, nacionales e internacionales, vienen afectando nuestro cotidiano. Logros que parecían firmados en el rumbo de la democracia y en los temas relacionados a los derechos humanos, logros sociales y consideraciones éticas en la vida política, vienen siendo sustituidos por clichés y discursos de odio, racismo y xenofobia bajo la lógica de la guerra. De este modo, flujo masivo de inmigrantes, fruto de guerras y violencias, ataques terroristas y una cotidiana tensión en la cual el debate localiza en el otro el peligro: se generaliza la figura del terrorista. Vamos a proponer un desplazamiento de la lógica de la guerra con la finalidad de dialogar sobre la caída de los ideales y de las ilusiones y las dificultades de trazar direcciones para el futuro. Vamos a enseñar la imbricada trama entre la ética del deseo, política y resistencia a la instrumentalización social del gozo. Entendemos que perder un ideal es diferente de perder una ilusión, creencia o delirio. La incredulidad, la desilusión, tiene sus efectos ­ uno de ellos es agarrarse a la fantasía delirante. La idealización es un proceso que envuelve el engrandecimiento y la súper estimación del objeto, sin relación con el ideal. La angustia psíquica nombrada "desilusión" se extiende de los ideales culturales (en el plan del ideal-del- yo) a las expectativas del Yo (plan del Yo-ideal). Esta cuestión nos alerta para el encubrimiento de otra ilusión, de auto creación, de poder superar la dependencia simbólica del Otro. Diferenciar estos términos nos permite apuntar la imbricada trama entre ética del deseo, política y la resistencia a la instrumentación social del gozo. Cuanto a la posición del psicoanálisis, retomaremos la frase de Lacan en Ciencia y verdad (1966/1998): "Siempre somos responsables por nuestra posición de sujeto. Que llamen esto como quieran, terrorismo".

Des événements sociaux et politiques, nationaux et internationaux, troublent notre vie quotidienne. Des réalisations qui semblaient consolidées vers la démocratie et chez les droits l'homme; bien comme des réalisations sociales et de la pensée éthique dans la vie politique, sont remplacées par des discours de haine, de racisme et de xénophobie sous la logique de la guerre. De cette façon, des flux massifs des immigrés, des fruits de la guerre et de la violence, des attaques terroristes et une tension quotidienne sont confrontés. Cela se passe dans le débat qui montre le danger dans l'autre: de la généralisation de la figure du terroriste. Dans cet article on propose un décalage de la logique de la guerre avec l>objectif de discuter de la chute des idéaux, et des illusions, bien comme des difficultés de tracer directions pour l'avenir. On signale la liaison compliquée entre l>éthique du désir, la politique et, aussi, la résistance à l>instrumentation sociale de la jouissance. On comprend que perdre un idéal est différent de perdre une illusion, de la croyance ou de l'illusion. L>incrédulité et la désillusion ont ses effets - l>un de ces effets est s>attacher à une fantaisie délirante. L>idéalisation est un processus qui contourne l>agrandissement et la surestimation de l>objet, sans faire rapport à l>idéal. L>affliction psychique appelée «désillusion¼ s>étend des idéaux culturels (sur le plan de l>idéal du Moi) aux attentes du Soi (plan idéal du moi). Cette question attire attention au camouflage d>autre illusion, d'auto-engendrement, de la possibilité de surmonter la dépendance symbolique de l>Autre. Différencier ces termes nous permet de montrer la liaison compliquée entre l'éthique du désir, la politique et, aussi, la résistance à l'instrumentation sociale de la jouissance. À propos de la position de la psychanalyse, on reprend la phrase de Lacan dans «La Science et la vérité¼ (1966/1998): «De notre position de sujet, nous sommes toujours responsables. Qu>on appellent cela où l>on veut, du terrorisme.¼.

Acute kidney injury and other factors associated with mortality in hiv-infected patients

SUMMARY OBJECTIVE: HIV-related mortality is still high, especially in developed countries. The aim of this study is to investigate factors associated to death in HIV-infected patients. METHODS: This is a cross-sectional study with all HIV adult patients admitted to a tertiary infectious diseases hospital in Fortaleza, Northeast Brazil, from January 2013 to December 2014. Patients were divided into two groups: survivors and non-survivors. Demo-graphical, clinical and laboratory data were compared and a logistic regression was performed in order to investigate risk factors for death. P values ≤0.05 were considered statistically significant. RESULTS: A total of 200 patients with mean age of 39 years were including in the study, 69.5% males. Fifteen patients (7.5%) died. Non-survivors presented a higher percentage of males (93.3 vs. 67.3%, p = 0.037). Non-survivors presented AKI (73.3 vs. 10.3%, p < 0.001), liver dysfunction (33.3 vs. 11.5, p = 0.031), dyspnea (73.3 vs. 33.0%, p = 0.002) and disorientation (33.3 vs. 12.4%, p = 0.025) more frequently. Non-survivors also had higher levels of urea (73.8 ± 52.7vs. 36.1 ± 29.1 mg/dL, p < 0.001), creatinine (1.98 ± 1.65 vs. 1.05 ± 1.07 mg/dL, p < 0.001), aspartate aminotransferase (130.8 vs. 84.8 U/L, p = 0.03), alanine aminotransferase (115.6 vs. 85.4 U/L, p = 0.045) and lactate dehydrogenase (LDH) (1208 vs. 608 U/L, p = 0.012), as well as lower levels of bicarbonate (18.0 ± 4.7 vs. 21.6 ± 4.6 mEq/L, p = 0.016) and PCO2 (27.8 ± 7.7 vs. 33.0 ± 9.3 mmHg, p = 0.05). In multivariate analysis, disorientation (p = 0.035, OR = 5.523, 95%CI = 1.130 - 26.998), dyspnoea (p = 0.046, OR = 4.064, 95%CI = 1.028 - 16.073), AKI (p < 0.001, OR = 18.045, 95%CI = 4.308 - 75.596) and disseminated histoplasmosis (p = 0.016, OR = 12.696, 95%CI = 1.618 - 99.646) and LDH > 1000 U/L (p = 0.038, OR = 4.854, 95%CI = 1.093 - 21.739) were risk factors for death.]CONCLUSION: AKI and disseminated histoplasmosis (DH) were the main risk factors for death in the studied population. Neurologic and respiratory impairment as well as higher levels of LDH also increased mortality in HIV-infected patients.

RESUMO INTRODUÇÃO: A mortalidade relacionada ao HIV ainda é alta, especialmente nos países em desenvolvimento. O objetivo deste estudo é investigar os fatores associados ao óbito em pacientes com HIV. MÉTODOS: Trata-se de um estudo transversal com todos os pacientes com HIV admitidos consecutivamente em um hospital terciário de doenças infecciosas em Fortaleza, Nordeste do Brasil, entre janeiro de 2013 e dezembro de 2014. Os pacientes foram divididos em dois grupos: sobreviventes e não sobreviventes. Dados demográficos, clínicos e laboratoriais foram comparados e análise de regressão logística foi feita para investigação dos fatores de risco para óbito. RESULTADOS: Um total de 200 pacientes, com média de idade de 39 anos, foi incluído no estudo, sendo 69,5% do sexo masculino. Óbito ocorreu em 15 pacientes (7,5%). Os não sobreviventes apresentaram maior percentual de homens (93,3 vs. 67,3%, p = 0,037) e um menor tempo de internação (8 ± 6 vs. 18 ± 15 dias, p = 0,005). Na análise multivariada, desorientação (p = 0,035, OR = 5,523), dispneia (p = 0,046, OR = 4,064), LRA (p < 0,001, OR = 18,045), histoplasmose disseminada (p = 0,016, OR = 12,696) e desidrogenase lática (LDH) > 1.000 U/L (p = 0,038, OR = 4,854) foram fatores de risco para óbito. CONCLUSÕES: LRA e histoplasmose disseminada foram os principais fatores de risco para óbito na população estudada. Distúrbios neurológicos e respiratórios, bem como níveis elevados de LDH, também estiveram associados com o aumento da mortalidade em pacientes com HIV.