Transient Symptomatic Zinc Deficiency in an Exclusively Breastfed Infant

A 3-month-old, full term female infant, adequate for gestational age, and exclusively breastfed, was admitted with a 10 day history of generalised scaling erythematous dermatitis, affecting the face (perinasal, nasolabial folds and periauricular), acral and intertriginous areas, with irritability and failure to thrive. Her mother had been treated with isoniazid since the third trimester because of family contact with tuberculosis. Based on a diagnosis of suspected impetiginised eczema, the infant was treated with flucloxacillin and prednisolone, and maternal isoniazid was suspended, with no improvement. Investigations found low serum zinc levels in the infant (33 μg/dL; normal range (NR) >60 μg/dL), normal plasma zinc levels in the mother (111.3 μg/dL; NR 68-120 μg/dL) and lower than the normal range of zinc levels in breast milk (270μg/L; NR 1000-2500 μg/L), suggesting acrodermatitis caused by zinc deficiency. Oral zinc supplementation (3 mg/kg/day) was started with a marked improvement in skin lesions, as well as good weight gain. At the age of 6 months, after food diversification, supplementation was suspended, without any recurrence of symptoms.info:eu-repo/semantics/publishedVersio

Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis

Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS) or peptidoglycan (PGN) induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation, proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the transcriptional diversity of primary human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGESeq approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (Kegg) analysis showed marked enrichment of immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators, negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome sequencing of stimulated/restimulated iDCs identified numerous genes with altered expression to date not associated with role in chronic inflammation, underlying the relevance of our in vitro model for further characterization of IFNprimed iDCs

Xylodiol from Xylopia langsdorfiana induces apoptosis in HL60 cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)An atisane diterpene was isolated from Xylopia langsdorfi ana St. Hilaire & Tulasne, Annonaceae, leaves, ent-atisane-7 alpha, 16 alpha-diol (xylodiol). Preliminary study showed that xylodiol was cytotoxic and induced differentiation on human leukemia cell lines. However, the molecular mechanisms of xylodiol-mediated cytotoxicity have not been fully defined. Thus, we investigated the anti-tumor effect of xylodiol in human leukemia HL60 cell line. Xylodiol induced apoptosis and necrosis. HL60 cells treated with xylodiol showed biochemical changes characteristic of apoptosis, including caspases-8, -9 and -3 activation and loss of mitochondrial transmembrane potential (Delta psi(m)). However, there was a condensation rather than swelling of mitochondria. Moreover, the formation of condensed mitochondria and the loss of Delta psi(m) occurred downstream of caspase activation. Cyclosporine A did not protect HL60 cells from the cytotoxic effects of xylodiol, suggesting that the loss of Delta psi(m) is a late event in xylodiol-induced apoptosis. Oxidative stress was involved in xylodiol-induced apoptosis. Thus, we conclude that activated caspases cleave cellular proteins resulting in mitochondrial damage leading to mitochondrial condensation, loss of Delta psi(m) and ROS release from the mitochondria. ROS can further induce and maintain a collapse of Delta psi(m) leading to cellular damage through oxidation of lipids and proteins resulting in apoptotic cell death.21610351042Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

OBJECTIVE: To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers. METHODS: Participants included patients with a mutation in MAPT, PGRN, or C9orf72, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers. RESULTS: A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings. CONCLUSIONS: Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD

A new approach to bad news effects on volatilit y: the multiple-sign-volume sensitive regime EGARCH model (MSV-EGARCH)

In this paper, using daily data for six major international stock market indexes and a modified EGARCH specification, the links between stock market returns, volatility and trading volume are investigated in a new nonlinear conditional variance framework with multiple regimes and volume eff ects. Volatility forecast comparisons, using the Harvey-Newbold test for multiple forecasts encompassing, seem to demonstrate that the MSV- EGARCH complex threshold structure is able to correctly fit GARCH- type dynamics of the series under study and dominates competing standard asymmetric models in several of the considered stock indexes.info:eu-repo/semantics/publishedVersio

Genetic variability in five populations of Partamona helleri (Hymenoptera, Apidae) from Minas Gerais State, Brazil

Partamona is a Neotropical genus of stingless bees that comprises 33 species distributed from Mexico to southern Brazil. These bees are well-adapted to anthropic environments and build their nests in several substrates. In this study, 66 colonies of Partamona helleri from five localities in the Brazilian state of Minas Gerais (São Miguel do Anta, Teixeiras, Porto Firme, Viçosa and Rio Vermelho) were analyzed using nine microsatellite loci in order to assess their genetic variability. Low levels of observed (Ho = 0.099-0.137) and expected (H e = 0.128-0.145) heterozygosity were encountered and revealed discrete genetic differentiation among the populations (F ST = 0.025). AMOVA further showed that most of the total genetic variation (94.24%) in P. helleri was explained by the variability within local populations

Comparative Anatomical Analyses of the Forearm Muscles of Cebus libidinosus (Rylands et al. 2000): Manipulatory Behavior and Tool Use

The present study describes the flexor and extensor muscles in Cebus libidinosus' forearm and compares them with those from humans, chimpanzees and baboons. The data is presented in quantitative anatomical indices for similarity. The capuchin forearm muscles showed important similarities with chimpanzees and humans, particularly those that act on thumb motion and allow certain degree of independence from other hand structures, even though their configuration does not enable a true opposable thumb. The characteristics of Cebus' forearm muscles corroborate the evolutionary convergence towards an adaptive behavior (tool use) between Cebus genus and apes