Sickle Cell Disease and Cerebrovascular Stroke: A Preventable Event

Introdução: Na criança, a etiologia do acidente vascular cerebral (AVC) é conhecida em 75% dos casos, sendo a anemia de células falciformes (ACF) a mais frequente na criança de raça negra. O interesse deste caso clínico reside na forma de apresentação pouco habitual e curso evitável. Caso clínico: Criança de raça negra com 27 meses de idade, sem antecedentes relevantes, admitida por sinais neurológicos focais de instalação súbita. A tomografia computorizada cranio-encefálica e ressonância magnética evidenciaram lesão isquémica aguda extensa e alterações compatíveis com AVC silencioso prévio. Analiticamente apresentava anemia normocítica, muitos drepanocitos de formação espontânea e 87% de hemoglobina S. Neste contexto, foi submetida a transfusão-permuta. Conclusão: O AVC como complicação da ACF pode acontecer em idades precoces e surgir como quadro inaugural. Pensamos que se justifica divulgar o rastreio pré-natal e realizar um estudo da relação custo-benefício para a implementação de um rastreio neonatal desta patologia em Portugal

Exsudative hypertrophic gastropathy in children: a rare disease?

A quarterly alumni newsletter. In this issue: foster care research; special legislative session; Oregon Teacher of the Year; feature on volleyball coach Marlene Piper.https://pdxscholar.library.pdx.edu/perspective/1071/thumbnail.jp

The blp locus of Streptococcus pneumoniae plays a limited role in the selection of which strains can co-colonize the human nasopharynx.

Nasopharyngeal colonization is important for Streptococcus pneumoniae evolution, providing the opportunity for horizontal gene transfer when multiple strains co-occur. Although colonization with more than one strain of pneumococcus is common, the factors that influence the ability of strains to co-exist are not known. A highly variable blp (bacteriocin-like peptide) locus has been identified in all sequenced strains of S. pneumoniae This locus controls the regulation and secretion of bacteriocins, small peptides that target other bacteria. In this study, we analyzed a series of co-colonizing isolates to evaluate the impact of the blp locus on human colonization to determine whether competitive phenotypes of bacteriocin secretion restrict co-colonization.We identified a collection of 135 nasopharyngeal samples with two or more strains totaling 285 isolates. The blp locus of all strains was characterized genetically with regards to pheromone type, bacteriocin/immunity content and potential for locus functionality. Inhibitory phenotypes of bacteriocin secretion and locus activity were assessed through overlay assays. Isolates from single colonization (n=298) were characterized for comparison.Co-colonizing strains had a high diversity of blp cassettes; approximately one third displayed an inhibitory phenotype in vitro Despite in vitro evidence of competition, pneumococci co-colonized individuals independently of their blp pheromone type (p=0.577), bacteriocin/immunity content, blp locus activity (p=0.798) and inhibitory phenotype (p=0.716). In addition, no significant differences were observed when single and co-colonizing strains were compared.Despite clear evidence of blp-mediated competition in experimental models, our study suggests that the blp locus plays a limited role in restricting pneumococcal co-colonization in humans. IMPORTANCE: Nasopharyngeal colonization with Streptococcus pneumoniae (pneumococcus) is important for pneumococcal evolution as it represents the major site for horizontal gene transfer when multiple strains co-occur, a phenomenon known as co-colonization. Understanding how pneumococcal strains interact within the competitive environment of the nasopharynx is of chief importance in the context of pneumococcal ecology. In this study we used an unbiased collection of naturally co-occurring pneumococcal strains and showed that a biological process frequently used by bacteria for competition - bacteriocin production - is not decisive in the co-existence of pneumococci in the host, contrary to what has been shown in experimental models

mTOR pathway overactivation in BRAF mutated papillary thyroid carcinoma

CONTEXT: There are several genetic and molecular evidences suggesting dysregulation of the mammalian target of rapamycin (mTOR) pathway in thyroid neoplasia. Activation of the phosphatidylinositol-3-kinase/AKT pathway by RET/PTC and mutant RAS has already been demonstrated, but no data have been reported for the BRAF(V600E) mutation. OBJECTIVE: The aim of this study was to evaluate the activation pattern of the mTOR pathway in malignant thyroid lesions and whether it may be correlated with known genetic alterations, as well as to explore the mechanisms underlying mTOR pathway activation in these neoplasias. RESULTS: We observed, by immunohistochemical evaluation, an up-regulation/activation of the mTOR pathway proteins in thyroid cancer, particularly in conventional papillary thyroid carcinoma (cPTC). Overactivation of the mTOR signaling was particularly evident in cPTC samples harboring the BRAF(V600E) mutation. Transfection assays with BRAF expression vectors as well as BRAF knockdown by small interfering RNA revealed a positive association between BRAF expression and mTOR pathway activation, which appears to be mediated by pLKB1 Ser428, and emerged as a possible mechanism contributing to the association between BRAF mutation and mTOR pathway up-regulation. When we evaluated the rapamycin in the growth of thyroid cancer cell lines, we detected that cell lines with activating mutations in the MAPK pathway show a higher sensitivity to this drug. CONCLUSIONS: We determined that the AKT/mTOR pathway is particularly overactivated in human cPTC harboring the BRAF(V600E) mutation. Moreover, our results suggest that the mTOR pathway could be a good target to enhance therapy effects in certain types of thyroid carcinoma, namely in those harboring the BRAF(V600E) mutation

Identification of Streptococcus pneumoniae by a real-time PCR assay targeting SP2020.

Real-time PCR targeting lytA (the major autolysin gene) and piaB (permease gene of the pia ABC transporter) are currently used as the gold-standard culture-independent assays for Streptococcus pneumoniae identification. We evaluated the performance of a new real-time PCR assay - targeting SP2020 (putative transcriptional regulator gene) - and compared its performance with the assays previously described. A collection of 150 pneumococci, 433 non-pneumococci and 240 polymicrobial samples (obtained from nasopharynx, oropharynx, and saliva; 80 from each site) was tested. SP2020 and lytA-CDC assays had the best performance (sensitivity of 100% for each compared to 95.3% for piaB). The specificity for lytA and piaB was 99.5% and for SP2020 was 99.8%. Misidentifications occurred for the three genes: lytA, piaB and SP2020 were found in non-pneumococcal strains; piaB was absent in some pneumococci including a serotype 6B strain. Combining lytA and SP2020 assays resulted in no misidentifications. Most polymicrobial samples (88.8%) yielded concordant results for the three molecular targets. The remaining samples seemed to contain non-typeable pneumococci (0.8%), and non-pneumococci positive for lytA (1.7%) or SP2020 (8.7%). We propose that combined detection of both lytA-CDC and SP2020 is a powerful strategy for the identification of pneumococcus either in pure cultures or in polymicrobial samples

Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells on rat sciatic nerve regeneration after end-to-end repair

Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat