Application of PolyPRep tools on HIV protease polyproteins using molecular docking

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking / Aplicação da ferramenta PolyPRep em poliproteínas de protease de HIV usando docking molecular

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

The schistosomicidal activity of ethanolic extracts from branches, leaves, flowers and fruits of Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) plant and metabolic profile characterization by UPLC-ESI-QTOF analysis.

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

Factors associated with the time taken for diagnosis of amyotrophic lateral sclerosis (ALS) in Brazil. An online population-based inquiry. / Factores asociados al tiempo necesario para el diagnóstico de esclerosis lateral amiotrófica (ELA) en Brasil. Una encuesta poblacional en línea.

OBJECTIVE: This study evaluated factors associated with the time, in months, between the onset of symptoms and the diagnosis (time taken for diagnosis) of ALS for patients in Brazil, in the year 2014. PATIENTS AND METHODS: An electronic questionnaire composed of 38 questions was developed and applied through internet-based social networks of patients. From the 210 replies, 194 were considered (86 from women, 108 from men). Most respondents were 51 to 60 years old. The Mann-Whitney test was used to compare the time taken for diagnosis between the strata of the sample. RESULTS: The mean time taken for diagnosis was 14.21 (±16.87) months. There was a statistically significant difference only for higher education conditions (p = 0.009) and low education status (p = 0.042). There was no statistically significant difference between sexes, bulbar onset, age groups, and the presence of spouse, or 'partnership with ALS patients associations or exchange of experiences'. CONCLUSION: These data suggest that the time taken for diagnosis of ALS is influenced by socioeconomic conditions that promote access to information and/or health services.

TITLE: Factores asociados al tiempo necesario para el diagnóstico de esclerosis lateral amiotrófica (ELA) en Brasil. Una encuesta poblacional en línea.Objetivo. Este estudio evaluó los factores asociados con el tiempo, en meses, entre el inicio de los síntomas y el diagnóstico (tiempo necesario para el diagnóstico) de esclerosis lateral amiotrófica (ELA) de los pacientes en Brasil en 2014. Pacientes y métodos. Se elaboró un cuestionario electrónico compuesto por 38 preguntas y se aplicó a través de redes sociales de pacientes basadas en Internet. De las 210 respuestas, se consideraron 194 (86 de mujeres y 108 de hombres). La mayoría de los encuestados tenía entre 51 y 60 años. Se utilizó la prueba de Mann-Whitney para comparar el tiempo transcurrido hasta el diagnóstico entre los estratos de la muestra. Resultados. El tiempo medio transcurrido hasta el diagnóstico fue de 14,21 (±16,87) meses. Hubo una diferencia estadísticamente significativa sólo para las condiciones de educación superior (p = 0,009) y bajo nivel educativo (p = 0,042). No hubo diferencias estadísticamente significativas entre sexos, inicio bulbar, grupos de edad y presencia de cónyuge, o colaboración con asociaciones de pacientes con ELA o intercambio de experiencias. Conclusión. Estos datos sugieren que el tiempo que se tarda en diagnosticar la ELA está influido por las condiciones socioeconómicas que favorecen el acceso a la información y/o a los servicios sanitarios.

Factores asociados al tiempo necesario para el diagnóstico de esclerosis lateral amiotrófica (ELA) en Brasil. Una encuesta poblacional en línea / Factors associated with the time taken for diagnosis of amyotrophic lateral sclerosis (ALS) in Brazil. An online population-based inquiry

Objetivo: Este estudio evaluó los factores asociados con el tiempo, en meses, entre el inicio de los síntomas y el diagnóstico (tiempo necesario para el diagnóstico) de esclerosis lateral amiotrófica (ELA) de los pacientes en Brasil en 2014.Pacientes y métodosSe elaboró un cuestionario electrónico compuesto por 38 preguntas y se aplicó a través de redes sociales de pacientes basadas en Internet. De las 210 respuestas, se consideraron 194 (86 de mujeres y 108 de hombres). La mayoría de los encuestados tenía entre 51 y 60 años. Se utilizó la prueba de Mann-Whitney para comparar el tiempo transcurrido hasta el diagnóstico entre los estratos de la muestra.ResultadosEl tiempo medio transcurrido hasta el diagnóstico fue de 14,21 (±16,87) meses. Hubo una diferencia estadísticamente significativa sólo para las condiciones de educación superior (p = 0,009) y bajo nivel educativo (p = 0,042). No hubo diferencias estadísticamente significativas entre sexos, inicio bulbar, grupos de edad y presencia de cónyuge, o colaboración con asociaciones de pacientes con ELA o intercambio de experiencias.ConclusiónEstos datos sugieren que el tiempo que se tarda en diagnosticar la ELA está influido por las condiciones socioeconómicas que favorecen el acceso a la información y/o a los servicios sanitarios. (AU)

OBJECTIVE. This study evaluated factors associated with the time, in months, between the onset of symptoms and the diagnosis (time taken for diagnosis) of ALS for patients in Brazil, in the year 2014.PATIENTS AND METHODSAn electronic questionnaire composed of 38 questions was developed and applied through internet-based social networks of patients. From the 210 replies, 194 were considered (86 from women, 108 from men). Most respondents were 51 to 60 years old. The Mann-Whitney test was used to compare the time taken for diagnosis between the strata of the sample.RESULTSThe mean time taken for diagnosis was 14.21 (±16.87) months. There was a statistically significant difference only for higher education conditions (p = 0.009) and low education status (p = 0.042). There was no statistically significant difference between sexes, bulbar onset, age groups, and the presence of spouse, or ‘partnership with ALS patients associations or exchange of experiences’. CONCLUSION. These data suggest that the time taken for diagnosis of ALS is influenced by socioeconomic conditions that promote access to information and/or health services. (AU)

Microbiological evaluation of homemade mayonnaise and self-serve acai sold in Araguaína, Tocantins.

Foodborne diseases are common illnesses caused by the consumption of food contaminated with microorganisms, such as viruses, fungi, bacteria, and protozoa. Every year, 600 million people become ill and 420,000 people die as a result of consuming contaminated food. Therefore, food safety is an important issue. In this study, samples of homemade spiced mayonnaise and self-serve acai sold in the city of Araguaína, Tocantins, Brazil were analyzed for microbiological contaminants. Acai was collected from 10 stores, one sample from each store, and tested for mold, yeast, and coliforms, as well as coliform identification and total and thermotolerant coliform counts. Mayonnaise was collected from 20 snack bars, one sample from each. These samples were inoculated on MacConkey and Salmonella Shigella agar plates, and the plates were analyzed for growth. Salmonella spp. were detected in some Mayonnaise samples, and coliforms were detected in all acai samples; 60% of samples had thermotolerant coliforms, and only 40% were within the limits established by ANVISA. The collected samples of mayonnaise and acai were contaminated with molds and yeasts above the established limit of 103 CFU/g. Thus, the analyzed mayonnaise and acai samples were contaminated and unfit for consumption, demonstrating the importance of hygienic-sanitary measures in food handling.

Polyphyly of the Dinurinae Looss, 1907 (Digenea: Hemiuridae) and resurrection of the Mecoderinae Skrjabin & Guschanskaja, 1954 based on novel collection of Tubulovesicula laticaudi Parukhin, 1969 from marine elapid snakes in Sri Lanka.

With one exception, the only known hemiurid trematodes that do not use teleost fishes as definitive hosts instead occur in marine elapid snakes. These comprise six species across four genera and three subfamilies, and so presumably indicate at least three independent invasions of marine snakes from teleost fishes. Here, one of these taxa, Tubulovesicula laticaudi Parukhin, 1969 (= T. orientalis Chattopadhyaya, 1970 n. syn.) is reported from Sri Lanka, collected from Shaw's sea snake Hydrophis curtus (Shaw) (Elapidae: Hydrophiinae: Hydrophinii), the annulated sea snake H. cyanocinctus Daudin and the yellow sea snake H. spiralis (Shaw) off Nayaru in the Bay of Bengal, and from H. spiralis in Portugal Bay, Gulf of Mannar. Novel molecular data, for COI mtDNA and ITS2 and 28S rDNA, are the first for a species of Tubulovesicula Yamaguti, 1934. Nominally, Tubulovesicula belongs in the Dinurinae Looss, 1907, but in phylogenetic analyses based on 28S rDNA, our sequences for T. laticaudi resolved relatively distant from that for representatives of Dinurus Looss, 1907, the type-genus, rendering the subfamily polyphyletic. Tubulovesicula laticaudi resolved closest to data for the type-species of the Plerurinae Gibson & Bray, 1979, but that subfamily is also polyphyletic. These findings lead us to re-evaluate an alternative classification considered by Gibson & Bray (1979). We propose restricting the Dinurinae for forms with a permanent sinus-organ (Dinurus, Ectenurus Looss, 1907; Erilepturus Woolcock, 1935; Paradinurus Vigueras, 1958; Qadriana Bilqees, 1971) and resurrect the Mecoderinae Skrjabin & Guschanskaja, 1954 for forms with a temporary sinus-organ (Mecoderus Manter, 1940, Allostomachicola Yamaguti, 1958, Stomachicola Yamaguti, 1934 and Tubulovesicula).

The KMT2A recombinome of acute leukemias in 2023.

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

Cat-eyed snake (Genus: Boiga) bites in Sri Lanka: First authentic case series.

Cat snakes (Genus: Boiga) are considered to be of lesser medical important in Sri Lanka, as their bites are known to cause only mild local effects such as local pain and swelling at the site of the bite. Five species of cat snakes are found in Sri Lanka, of which three are endemic. They are widely distributed all over the country. Out of seven cases of cat snake bites, including six adults and one child, five developed only mild local effects and two did not have any symptoms. Any of them did not develop systemic manifestations. The snakes responsible were the Sri Lanka cat snake (Boiga ceylonensis), Forsten's cat snake (Boiga forsteni), and also Ranawana's cat snake (Boiga ranawanei) which is the first report in Sri Lanka.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking.

In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Antibiotic misuse: How to evaluate the costs?

OBJECTIVE: Few studies have assessed the costs associated with the misuse of antibiotics in hospitals in France, despite the value of health economic data to inform antibiotic stewardship activities. We aimed to identify the methodological tools used to assess the cost of antibiotic misuse in hospitals. METHODS: We performed a literature review using the major electronic medical databases. An index of relevance was developed to assess the intrinsic quality of selected articles. RESULTS: Four hundred and three articles were retrieved, but 35 were selected for analysis. Most studies investigated the inadequate choice of the antibiotic molecule (n=17), the incorrect treatment duration (n=9), and the administration of an inappropriate dosage (n=7). Only three studies were medical/economic evaluations of specific interventions, such as prescription control by pharmacists or the implementation of a new diagnostic test. Considering our aim, the relevance of the studies was limited: few had defined the economic assessment as the primary objective or had detailed the method for calculating costs. Nevertheless, the misuse evaluation was usually better described. CONCLUSIONS: Despite these limits, key factors for measuring antibiotic misuse (i.e., molecule choice, dosage) in relation to the costs (i.e., over/under prescription, hospital stay, staff remuneration) might serve as the basis for the development of a reference methodology to value the costs of misuse. The application of this methodology on identified situations of antibiotic misuse would help hospital decision-makers to justify resource allocation for implementing antimicrobial stewardship activities.

Influence of parasite load on the diagnosis and occurrence of eosinophilia in alcoholic patients infected with Strongyloides stercoralis.

Alcoholic patients are more susceptible to Strongyloides stercoralis infection. The chronic use of alcohol raises the levels of endogenous corticosteroids, which regulates the development of larvae and stimulates the differentiation of rhabditiform into infective filariform larvae, thus inducing internal autoinfection. Therefore, early diagnosis is important to prevent severe strongyloidiasis. The aim of this study was to evaluate the efficacy of parasitological methods, according to the parasite load and the number of stool samples, for diagnosis of S. stercoralis infection, as well the peripheral blood eosinophil count in alcoholic patients. A total of 330 patients were included in this study. The diagnosis was established using three parasitological methods: agar plate culture, Baermann-Moraes method and spontaneous sedimentation. Peripheral eosinophilia was considered when the level was >600 eosinophils/mm3. The agar plate culture (APC) had the highest sensitivity (97.3%). However, the analysis of multiple samples increased the sensitivity of all parasitological methods. The sensitivities of the methods were influenced by the parasite load. When the larval number was above 10, the sensitivity of APC was 100%, while in spontaneous sedimentation the sensitivity reached 100% when the larval number was above 50. In the present study, 15.4% of alcoholic patients infected with S. stercoralis (12/78) had increased peripheral blood eosinophil count (above 600 eosinophils/mm3). For an efficient parasitological diagnosis of S. stercoralis infection in alcoholic patients, repeated examination by two parasitological methods must be recommended, including agar plate culture due to its higher sensitivity. Moreover, S. stercoralis infection was associated with eosinophilia, mostly in patients excreting up to 10 larvae/g faeces.

High frequency of genital carriers of Leptospira sp. in sheep slaughtered in the semi-arid region of northeastern Brazil.

Although some studies in sheep have indicated leptospire colonization of the genital tract, further studies are needed to clarify the role of genital carriers in this species. Thus, this study aimed to evaluate the colonization of pathogenic leptospires in the genital and urinary tract of slaughtered sheep. Fifty-seven adult, female woolless sheep destined for slaughter were used. Renal (n = 57), bladder (n = 57), ovary (n = 34), uterine tube (n = 44), and uterus (n = 33) samples were collected for molecular detection of Leptospira sp. DNA, and blood samples (n = 57) for serological testing. The molecular testing was performed using polymerase chain reaction (PCR), and the serological testing was performed using microscopic serum agglutination test (MAT). Samples with amplifying DNA were subjected to genetic sequencing. In total, leptospiral DNA was found in the tissues of 44 (77.2%) sheep, whereas only nine animals were positive on both PCR and MAT; there was slight agreement between PCR and MAT techniques (k = 0.0268; p = 0.684). In 61 (54.9%) genital tract and in five (4.4%) urinary tract samples, the leptospiral DNA was detected, with significant difference (p < 0.001). The genes of one sample from the uterine tube and another from the bladder were sequenced and demonstrated 99% similarity to Leptospira interrogans. Anti-Leptospira antibodies were detected in 11 (19.3%) of the tested animals. The results reinforce the importance of the genital tract as an extra-renal site of colonization, suggesting the possibility of venereal transmission in sheep.

Apparent metabolisable energy and amino acid digestibility of microalgae Spirulina platensis as an ingredient in broiler chicken diets.

1. This work investigates the apparent metabolisable energy (AME), its nitrogen-corrected form (AMEn) and amino acid (AA) digestibility coefficients of the microalgae Spirulina platensis as an ingredient in broiler chicken diets. 2. One group of birds was fed with a basal control diet (BD), and another was fed with a test diet composed of the BD with the addition of the microalgae at a proportion of 200 g/kg. AME and AMEn were assessed by total excreta collection and indigestibility analysis using acid-insoluble ash (AIA) as a marker. 3. The microalgae comprised 888.0 g/kg dry matter (DM), 18.42 MJ/kg gross energy, 514.7 g/kg crude protein, 9.9 g/kg ether extract, 10.6 g/kg crude fibre, 94.4 g/kg ash, 3.1 g/kg Ca and 11.0 g/kg P. 4. The values obtained for AME (13.48 MJ/kg DM) and AMEn (11.72 MJ/kg DM) were higher (p < 0.01) than those obtained using the AIA method (9.39-8.29 MJ/kg DM). The microalgae ileal digestibility coefficients were 0.80 ± 0.04 and 0.78 ± 0.04 for essential and non-essential AA, respectively. 5. Overall, the metabolisable energy content and digestibility of AA for S. platensis indicated that the microalgae are potentially an alternative nutrient source for broilers. The AIA method underestimated AME and AMEn in comparison to the total excreta collection method.

The MLL recombinome of acute leukemias in 2017.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

População de protozoários ruminais em novilhos zebuínos alimentados com ou sem volumoso / Population of Protozoa in zebu steers fed with or without bulk

This study aimed to quantify and identify the profile of the rumen protozoa population of beef steers fed with or without roughage. Nellore crossbred steers raised in extensive system on lignified tropical pastures with mineral supplementation and steers confined for 60 days only receiving pelletized concentrate and whole corn kernels were evaluated. After slaughter, rumen fluid was collected and one ml aliquots were diluted in nine ml formaldehyde solution at 10%. The counts of small, medium and large protozoa were held in Sedgewick Rafter chambers and identification of genus was possible after staining lugol and optical microscope with a 40X objective. The concentration of rumen protozoa positively correlated with pH ruminal. Cattle fed without roughage had significantly lower rumen protozoa population (P<0.05). Animals fed roughage had higher occurrence of Dasytrichia genus, Charonina, Entodinum, Diplodinium, Ostracodinium and Epidinium while those fed without bulk, the Buetschilia, Isotricha, Eodinium, Polyplastron, Elyplastron, Metadinium and Enoploplastron were the most frequent genus.(AU)

Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease.

Ethanol is an important risk factor for the occurrence of several brain disorders that depend on the amount, period and frequency of its consumption. Chronic use of ethanol often leads to the development of neurodegenerative syndromes, which cause morphological and functional impairments such as foetal alcohol syndrome in newborns exposed to ethanol during pregnancy, Wernicke-Korsakoff Syndrome and, more rarely, Marchiafava-Bignami disease (MBD). MBD is characterized by primary degeneration of the corpus callosum, without inflammation and is associated with oxidative stress and hypovitaminosis, as well as altered mental status, to mention dementia, seizures, depression and so on. This review discusses MBD and poor nutrition as a risk factor for the development of such alcoholic syndrome, with focus on diagnosis, pathogenic aspects, signs and symptoms, as well as therapeutic perspectives. On the basis of the inclusion/exclusion criteria adopted, the performed search in scientific databases (Pubmed, Scielo and Google Scholar) resulted in 100 studies that are being presented and discussed in the present work. Review, case-control and cohort studies on alcoholism-associated hypovitaminosis, oxidative stress, MBD and ethanol metabolism pathways were admitted as relevant. We highlight that MBD is a poorly described, diagnosed, insidious and progressive condition, for which evidence suggests a synergism between ethanol-induced neurotoxic effects and hypovitaminosis B. Present treatment consists of vitamin B1(thiamine) supplementation. Nonetheless, other strategies such as the inclusion of antidepressants or steroidal anti-inflammatories as add-on therapies have been employed as an attempt to improve the damage. Indeed, both the diagnosis and treatment are difficult, and death occurs within few years.

Isolation and Characterization of Madariaga Virus from a Horse in Paraíba State, Brazil.

Madariaga virus (MADV), the new species designation for the South American isolates of eastern equine encephalitis virus (EEEV), is genetically divergent and substantially different in ecology and pathogenesis from North American EEEV strains. We isolated and characterized a MADV isolate obtained from a horse in Brazil. Our results support previous phylogenetic studies showing there are three genetically distinct MADV lineages. The MADV isolate from Paraíba State belongs to the South American lineage III and is closely related to Peruvian, Colombian and Venezuelan isolates.

5-ALA-mediated photodynamic therapy reduces the parasite load in mice infected with Leishmania braziliensis.

Photodynamic therapy (PDT) has proven to be an effective alternative for the treatment of cutaneous leishmaniasis. Skin lesions consist of ulcers with well-defined raised edges, and granular floor. Th1 immune response is the protective profile in patients infected with Leishmania. In this study, the photodynamic therapy with 5-aminolevulinic acid, the parasitic load, and the modulation of the immune response was evaluated in mice infected with Leishmania braziliensis. Balb/c mice were infected with L. braziliensis and subsequently treated with three sections of PDT. The parasite load and mRNA expression of cytokines (IFN-γ, IL-4, IL-17, IL-22, IL-27, IL-10) and transcription factors (GATA-3, Foxp3 and T-bet) were analysed by quantitative PCR. The parasite load in the treated group was significantly lower than in the untreated group (P<.0001); in PDT treated animals, we observed an increase in IFN-γ and T-bet mRNA (P=.012 and P=.0071). There was a significant reduction in mRNA expression of IL-22 associated with an increased expression of IL-27 mRNA in the animals treated with light only (P=.0001). 5-ALA associated with photodynamic therapy promotes a reduction in parasite load and an increased expression of IFN-γ and T-bet mRNA.