Distance-based phylogenetic inference from typing data: a unifying view.

Typing methods are widely used in the surveillance of infectious diseases, outbreaks investigation and studies of the natural history of an infection. Moreover, their use is becoming standard, in particular with the introduction of high-throughput sequencing. On the other hand, the data being generated are massive and many algorithms have been proposed for a phylogenetic analysis of typing data, addressing both correctness and scalability issues. Most of the distance-based algorithms for inferring phylogenetic trees follow the closest pair joining scheme. This is one of the approaches used in hierarchical clustering. Moreover, although phylogenetic inference algorithms may seem rather different, the main difference among them resides on how one defines cluster proximity and on which optimization criterion is used. Both cluster proximity and optimization criteria rely often on a model of evolution. In this work, we review, and we provide a unified view of these algorithms. This is an important step not only to better understand such algorithms but also to identify possible computational bottlenecks and improvements, important to deal with large data sets.

Analysis of the socio-environmental vulnerability of black and Caucasian pregnant women in Salvador, Bahia, Brazil to the occurrence of microcephaly associated with the congenital syndrome of zika virus.

To understand the occurrence of the Congenital Zika Syndrome (CZS), the living conditions of pregnant individuals must be considered in order to identify factors and areas of risk. An intersectional approach provides an understanding of the vulnerabilities to which Black women are subjected. To that end, we present an overview of the spatio-temporal distribution of confirmed cases of microcephaly associated with CZS during the 2015-2016 period in Salvador, Bahia, Brazil based on a survey of Black and Caucasian, pregnant women seen through the intersectional lens of race and class. To consider the confirmed cases of microcephaly and other neurological anomalies associated with CZS, a Living Condition Index (LCI) was utilized to rate the socio-environmental vulnerability of pregnant women. There was less information in the notification records with regard to Black, pregnant women resulting in fewer examinations. Twelve, highrisk areas for Black, pregnant women were identified but only two for Caucasian women. CZS cases referred to Black, pregnant women were found to be concentrated in census sectors with a low (31.6%) and very low (34.5%) LCI, while those referred to Caucasian, pregnant women were concentrated in areas with a high (35.6%) and intermediate (29.4%) LCI. The study concludes that inequities in health expose different population groups to different forms of illnesses, and institutional racism solidifies scenarios of exclusion. In this sense, Black women experiences manifest directly in their health. Confrontation with arboviruses requires the implementation of inter-institutional policies aimed at overcoming discriminatory practices of exposure.

Peptide R18H from BRN2 Transcription Factor POU Domain Displays Antitumor Activity In Vitro and In Vivo and Induces Apoptosis in B16F10-Nex2 Cells.

BACKGROUND: BRN2 transcription factor is associated with the development of malignant melanoma. The cytotoxic activities and cell death mechanism against B16F10-Nex2 cells were determined with synthetic peptide R18H derived from the POU domain of the BRN2 transcription factor. OBJECTIVE: To determine the cell death mechanisms and in vivo activity of peptide R18H derived from the POU domain of the BRN2 transcription factor against B16F10-Nex2 cells. METHODS: Cell viability was determined by the MTT method. C57Bl/6 mice were challenged with B16F10-Nex2 cells and treated with R18H. To identify the type of cell death, we used TUNEL assay, Annexin V and PI, Hoechst, DHE, and determination of caspase activation and cytochrome c release. Transmission electron microscopy was performed to verify morphological alterations after peptide treatment. RESULTS: Peptide R18H displayed antitumor activity in the first hours of treatment and the EC50% was calculated for 2 and 24h, being 0.76 ± 0.045 mM and 0.559 ± 0.053 mM, respectively. After 24h apoptosis was evident, based on DNA degradation, chromatin condensation, increase of superoxide anion production, phosphatidylserine translocation, activation of caspases 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. The peptide cytotoxic activity was not affected by necroptosis inhibitors and treated cells did not release LDH in the extracellular medium. Moreover, in vivo antitumor activity was observed following treatment with peptide R18H. CONCLUSION: Peptide R18H from BRN2 transcription factor induced apoptosis in B16F10-Nex2 and displayed antitumor activity in vivo.

PnTx2-6 (or δ-CNTX-Pn2a), a toxin from Phoneutria nigriventer spider venom, releases l-glutamate from rat brain synaptosomes involving Na+ and Ca2+ channels and changes protein expression at the blood-brain barrier.

PhTx2 is the most toxic fraction from the venom of the spider Phoneutria nigriventer, being responsible to sodium entry into cortical synaptosomes, increasing the release of neurotransmitters, such as l-glutamate (L-Glu) and; acetylcholine. In this study, we investigated the action of a toxin purified from; PhTx2 fraction, called PnTx2-6 or δ-CNTX-Pn2a, on L-Glu release from rat; brain cortex synaptosomes, as well as its ability to induce blood-brain barrier permeability. PnTx2-6 increased L-Glu release from rat cortical brain synaptosomes in a time- and dose-dependent manner (EC50 = ∼20 nM; Tm = 16min), as measured by a fluorimetric method. The increase of L-Glu by PnTx2-6 was inhibited by tetrodotoxin. And partially inhibited by EGTA. Calcium channel blockers ω-conotoxin MVIIC (P/Q-types) and ω-conotoxin GVIA (N-type), were able to reduce the PnTx2-6-induced release of L-Glu, while nifedipine (L-type) did not show any inhibition. These findings suggest that thew release of L-Glu by PnTx2-6 is due its primary action on sodium channels, well-known to be target of this toxin. PnTx2-6 is able to potentiate penile erection and this effect may be related with the release of l-glutamate from the CNS, besides a local effect on corpus carvenosum, as previously shown by our group. If L-Glu release and penile erection potentiation are indeed correlated, then this toxin should be able to cross the blood brain barrier (BBB). Results by immunoblotting assays indicated a change in the expression of proteins associated with the paracellular and transcellular transport at the blood-brain barrier, suggesting a BBB dysfunction mediated by PnTx2-6. Therefore, PnTx2-6 may induce the release l-glutamate in the central nervous system, when injected peripherally.

PHYLOViZ 2.0: providing scalable data integration and visualization for multiple phylogenetic inference methods.

High Throughput Sequencing provides a cost effective means of generating high resolution data for hundreds or even thousands of strains, and is rapidly superseding methodologies based on a few genomic loci. The wealth of genomic data deposited on public databases such as Sequence Read Archive/European Nucleotide Archive provides a powerful resource for evolutionary analysis and epidemiological surveillance. However, many of the analysis tools currently available do not scale well to these large datasets, nor provide the means to fully integrate ancillary data. Here we present PHYLOViZ 2.0, an extension of PHYLOViZ tool, a platform independent Java tool that allows phylogenetic inference and data visualization for large datasets of sequence based typing methods, including Single Nucleotide Polymorphism (SNP) and whole genome/core genome Multilocus Sequence Typing (wg/cgMLST) analysis. PHYLOViZ 2.0 incorporates new data analysis algorithms and new visualization modules, as well as the capability of saving projects for subsequent work or for dissemination of results. AVAILABILITY AND IMPLEMENTATION: http://www.phyloviz.net/ (licensed under GPLv3). CONTACT: cvaz@inesc-id.ptSupplementary information: Supplementary data are available at Bioinformatics online.

Precocious presentation of autoimmune polyglandular syndrome type 2 associated with an AIRE mutation.

Autoimmune polyglandular syndrome type 2 (type 2 APS), or Schmidt's syndrome, is defined by the presence of Addison's disease in combination with type 1 diabetes and/or autoimmune thyroid disease. The estimated prevalence of this syndrome is 1.4-4.5 per 100,000 inhabitants and it is more frequent in middle-aged females, whilst it is quite rare in children. Type 2 APS, which shows a pattern of autosomal dominant inheritance with low penetrance, has been associated with HLA specific DR3/DQ2 and DR4/DQ8 haplotypes. However, it has been hypothesized that genetic variability in the AIRE gene, which causing type 1 APS, may play a role in more common organ-specific autoimmune conditions like type 1 diabetes, Hashimoto's disease and type 2 APS, among others. Here we present the case of an 8-year-old girl, with a past medical history of type 1 diabetes diagnosed at the age of 3. She was taken to the Emergency Department because she complained of abdominal pain, nausea and vomiting, and her blood analysis revealed a severe hyponatremia. She also had seizures as a consequence of the hyponatremia and frequent hypoglycemia. She was ultimately found to be suffering from autoimmune primary adrenal insufficiency. The combination of both mentioned conditions, type 1 diabetes and Addison's disease, in the absence of chronic mucocutaneous candidiasis, made a diagnosis of type 2 APS plausible in this girl. The genetic study showed two heterozygous variants: NM_000383.2:C.1411C>T (p. Arg471Cys) in exon 12 and IVS9+6G>A in intron 9 of the AIRE gene. The description of an uncommon case of type 2 APS with precocious presentation associated with an AIRE mutation in a very young girl could help to clarify the role of AIRE in the development of autoimmune diseases.

Adrenoleukodystrophy: a forgotten diagnosis in children with primary Addison's disease.

The X linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by defects of the ABCD1 gene on chromosome Xq28 leading to accumulation of very long chain fatty acids (VLCFA), progressive demyelination and adrenal insufficiency. An 8-year-old boy was referred to our paediatric endocrinology clinic due to fatigue and hyperpigmentation with onset at 2-years old. Blood tests revealed mineralocorticoid insufficiency. Serum adrenocorticotropic hormone and cortisol concentrations were compatible with adrenal insufficiency. Adrenal antibodies were negative. The elevated plasmatic concentration of VLCFA and the genotype analysis with sequencing of ABCD1 gene established the diagnosis of X-ALD. Brain MRI showed demyelination of white matter in the peritrigonal regions. Steroid replacement was started with good response. He initiated restriction of VLCFA by reducing the intake of fatty foods. The authors highlight the importance of suspecting of X-ALD in the aetiology of primary adrenal insufficiency as the first sign of the disease.

Bloody nipple discharge in infancy--report of two cases.

Bloody nipple discharge (BND) in infancy is an exceptionally rare finding. We report the cases of two children who are 9 and 29 months old. The first case presented with 1 month of bilateral intermittent blood-stained nipple discharge with no other symptoms. The second case presented with 15 days of intermittent right BND and a small palpable mass, without obvious signs of inflammation. The coagulation and hormonal tests were within the age-appropriate reference ranges. Ultrasound examination was normal. Cytological evaluation of nipple discharge showed no malignant cells. Both patients had spontaneous symptoms resolution. BND in paediatric age is usually benign and self-limited and often related to mammary duct ectasia. Unnecessary invasive procedures or treatments should be avoided.

Rib osteomyelitis in a pediatric patient case report and literature review.

Rib osteomyelitis is a very rare form of childhood osteomyelitis. We describe a case of a 9-year-old child with an osteomyelitis of the rib due to Staphylococcus aureus and review 57 cases reported in the literature. This case demonstrates that the diagnosis of this uncommon disease requires a high index of suspicion due to its rarity and nonspecific signs.

De catador de lixo a agente ambiental: educação ambiental na qualidade de vida / From Being a Waste Collector to an Environmental Education Agent - Environmental Education in Quality of Life

A Cooperativa Amigos do Lixo de Guaratinguetá é uma iniciativa de um grupo da sociedade civil do município de Guaratinguetá, Estado de São Paulo, que se dedica voluntariamente à tarefa de arrecadar material reciclável e tem conquistado, de forma progressiva, o apoio de empresas privadas, de instituições públicas e da Prefeitura Municipal. Nasceu da necessidade de melhorar as condições de trabalho e de vida dos catadores de lixo do município, que atuavam de modo isolado no antigo lixão do município. Todas as atividades foram planejadas de modo a inserir a ação no âmbito mais geral de educação ambiental e sanitária, com ênfase na qualidade de vida e preservação do meio ambiente. Inicialmente, estes catadores foram identificados após pesquisa de campo, tiveram seu perfil sócio-econômico traçado, participaram de curso de capacitação profissional, após o qual passaram a atuar com identificação pessoal, uniforme e carrinhos padronizados em setores pré-estabelecidos da cidade, ficando conhecidos como Agentes Ambientais. Participam de curso de alfabetização, de eventos sócio-ambientais, ministram palestras e são responsáveis pelo programa de educação ambiental na comunidade e nas escolas. A partir do ano de 2005, a cooperativa passou a se preocupar com a responsabilidade social, implementando o projeto Vivendo e Aprendendo para os filhos dos cooperados e o Centro Sensorial de Geração de Renda e Educação Ambiental para os portadores de necessidades especiais. Desta forma, o objetivo do trabalho é avaliar e analisar a melhoria de qualidade de vida destes catadores, tendo como ferramenta de análise as atividades sócio-educativas desenvolvidas. Os resultados foram obtidos através de acompanhamento das atividades e das entrevistas com os catadores.

Da norma ao risco: transformações na produção de subjetividades contemporâneas / From norm to risk: transformation in the contemporary production of subjectivities

O objetivo do presente artigo é demonstrar, com base na premissa foucaultiana de que a resistência é sempre primeira, algumas transformações que se deram com o movimento social de recusa à sociedade disciplinar a partir de profundas mudanças nos processos de produção de subjetividade e de controle sobre os corpos e os comportamentos. As transformações em análise dizem respeito à passagem de uma sociedade fundada na normatização dos sujeitos para uma sociedade de controle dos riscos do cotidiano, o que permitiu, em grande parte, uma revitalização da capacidade de comando social do capitalismo sobre as pessoas. Resulta dessa análise, portanto, a apreensão de alguns mecanismos de poder que vêm sendo impostos e naturalizados hoje em dia e que subjetividades são produzidas por eles (AU)