Endovascular Treatment of Pediatric Ischemic Stroke: a Single Center Experience and Review of the Literature

Introduction: Mechanical thrombectomy is standard treatment for large vessel occlusion (LVO) in adults. There are no randomized controlled trials for the pediatric population. We report our single-center experience with thrombectomy of LVO in a series of pediatric patients, and perform a review of the literature. Methods: Retrospective review of consecutive pediatric thrombectomy cases between 2011 and 2018. Demographic variables, imaging data, technical aspects and clinical outcome were recorded. Results: In a period of 7 years, 7 children were treated for LVO at our center. Median age was 13 (2-17), and median Ped-NIHSS was 15 (3-24), and the median ASPECTS was 8 (2-10). Five patients had cardiac disease, and 2 of them were under external cardiac assistance. Median time from onset of symptoms to beginning of treatment was 7h06m (2h58m-21h38m). Five patients had middle cerebral artery occlusions. Thrombectomy was performed using a stentriever in 3 patients, aspiration in 3 patients, and combined technique in 1 patient. Six patients had good recanalization (TICI 2 b/3). There were no immediate periprocedural complications. At 3 months, 4 patients (57%) were independent (mRS score <3). Two patients died, one after haemorrhagic transformation of an extensive MCA infarct, and one due to extensive brainstem ischemia in the setting of varicella vasculitis. Discussion: Selected pediatric patients with LVO may be treated with mechanical thrombectomy safely. In patients under external cardiac assistance and under anticoagulation, thrombectomy is the only alternative for treatment of LVO. A multidisciplinary approach in specialized pediatric stroke centers with trained neurointerventionalists are essential for good results.info:eu-repo/semantics/publishedVersio

Heme Mediated STAT3 Activation in Severe Malaria

The mortality of severe malaria [cerebral malaria (CM), severe malaria anemia (SMA), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)] remains high despite the availability associated with adequate treatments. Recent studies in our laboratory and others have revealed a hitherto unknown correlation between chemokine CXCL10/CXCR3, Heme/HO-1 and STAT3 and cerebral malaria severity and mortality. Although Heme/HO-1 and CXCL10/CXCR3 interactions are directly involved in the pathogenesis of CM and fatal disease, the mechanism dictating how Heme/HO-1 and CXCL10/CXCR3 are expressed and regulated under these conditions is still unknown. We therefore tested the hypothesis that these factors share common signaling pathways and may be mutually regulated.We first clarified the roles of Heme/HO-1, CXCL10/CXCR3 and STAT3 in CM pathogenesis utilizing a well established experimental cerebral malaria mouse (ECM, P. berghei ANKA) model. Then, we further determined the mechanisms how STAT3 regulates HO-1 and CXCL10 as well as mutual regulation among them in CRL-2581, a murine endothelial cell line.The results demonstrate that (1) STAT3 is activated by P. berghei ANKA (PBA) infection in vivo and Heme in vitro. (2) Heme up-regulates HO-1 and CXCL10 production through STAT3 pathway, and regulates CXCL10 at the transcriptional level in vitro. (3) HO-1 transcription is positively regulated by CXCL10. (4) HO-1 regulates STAT3 signaling.Our data indicate that Heme/HO-1, CXCL10/CXCR3 and STAT3 molecules as well as related signaling pathways play very important roles in the pathogenesis of severe malaria. We conclude that these factors are mutually regulated and provide new opportunities to develop potential novel therapeutic targets that could be used to supplement traditional prophylactics and treatments for malaria and improve clinical outcomes while reducing malaria mortality. Our ultimate goal is to develop novel therapies targeting Heme or CXCL10-related biological signaling molecules associated with development of fatal malaria

A global characterization of the translational and transcriptional programs induced by methionine restriction through ribosome profiling and RNA-seq

Background: Among twenty amino acids, methionine has a special role as it is coded by the translation initiation codon and methionyl-tRNAi (Met-tRNAi) is required for the assembly of the translation initiation complex. Thus methionine may play a special role in global gene regulation. Methionine has also been known to play important roles in cell growth, development, cancer, and aging. In this work, we characterize the translational and transcriptional programs induced by methionine restriction (MetR) and investigate the potential mechanisms through which methionine regulates gene expression, using the budding yeast S. cerevisiae as the model organism. Results: Using ribosomal profiling and RNA-seq, we observed a broad spectrum of gene expression changes in response to MetR and identified hundreds of genes whose transcript level and/or translational efficiency changed significantly. These genes show clear functional themes, suggesting that cell slows down its growth and cell cycle progression and increases its stress resistance and maintenance in response to MetR. Interestingly, under MetR cell also decreases glycolysis and increases respiration, and increased respiration was linked to lifespan extension caused by caloric restriction. Analysis of genes whose translational efficiency changed significantly under MetR revealed different modes of translational regulation: 1) Ribosome loading patterns in the 5&apos;UTR and coding regions of genes with increased translational efficiency suggested mechanisms both similar and different from that for the translational regulation of Gcn4 under general amino acid starvation condition; 2) Genes with decreased translational efficiency showed strong enrichment of lysine, glutamine, and glutamate codons, supporting the model that methionine can regulate translation by controlling tRNA thiolation. Conclusions: MetR induced a broad spectrum of gene expression changes at both the transcriptional and translational levels, with clear functional themes indicative of the physiological state of the cell under MetR. Different modes of translational regulation were induced by MetR, including the regulation of the ribosome loading at 5&apos;UTR and regulation by tRNA thiolation. Since MetR extends the lifespan of many species, the list of genes we identified in this study can be good candidates for studying the mechanisms of lifespan extension.National Institutes of Health [AG043080]SCI(E)ARTICLE1

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma delta T cell subsets

The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology

Sickness behaviour pushed too far – the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines – generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbα) that control circadian rhythm – becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases

Changing Domesticity of Aedes aegypti in Northern Peninsular Malaysia: Reproductive Consequences and Potential Epidemiological Implications

BACKGROUND: The domestic dengue vector Aedes aegypti mosquitoes breed in indoor containers. However, in northern peninsular Malaysia, they show equal preference for breeding in both indoor and outdoor habitats. To evaluate the epidemiological implications of this peridomestic adaptation, we examined whether Ae. aegypti exhibits decreased survival, gonotrophic activity, and fecundity due to lack of host availability and the changing breeding behavior. METHODOLOGY/PRINCIPAL FINDINGS: This yearlong field surveillance identified Ae. aegypti breeding in outdoor containers on an enormous scale. Through a sequence of experiments incorporating outdoors and indoors adapting as well as adapted populations, we observed that indoors provided better environment for the survival of Ae. aegypti and the observed death patterns could be explained on the basis of a difference in body size. The duration of gonotrophic period was much shorter in large-bodied females. Fecundity tended to be greater in indoor acclimated females. We also found increased tendency to multiple feeding in outdoors adapted females, which were smaller in size compared to their outdoors breeding counterparts. CONCLUSION/SIGNIFICANCE: The data presented here suggest that acclimatization of Ae. aegypti to the outdoor environment may not decrease its lifespan or gonotrophic activity but rather increase breeding opportunities (increased number of discarded containers outdoors), the rate of larval development, but small body sizes at emergence. Size is likely to be correlated with disease transmission. In general, small size in Aedes females will favor increased blood-feeding frequency resulting in higher population sizes and disease occurrence

Analyzing factors that influence the folk use and phytonomy of 18 medicinal plants in Navarra

BACKGROUND: This article analyzes whether the distribution or area of use of 18 medicinal plants is influenced by ecological and cultural factors which might account for their traditional use and/or phytonymy in Navarra. This discussion may be helpful for comparative studies, touching as it does on other ethnopharmacological issues: a) which cultural and ecological factors affect the selection of medicinal plants; b) substitutions of medicinal plants in popular medicine; c) the relation between local nomenclature and uses. To analyze these questions, this paper presents an example of a species used for digestive disorders (tea and camomile: Jasonia glutinosa, J. tuberosa, Sideritis hyssopifolia, Bidens aurea, Chamaemelum nobile, Santolina chamaecyparissus...), high blood pressure (Rhamnus alaternus, Olea europaea...) or skin diseases (Hylotelephium maximum, H. telephium, Anagallis arvensis, A. foemina). METHODS: Fieldwork began on January 2004 and continued until December 2006. During that time we interviewed 505 informants in 218 locations in Navarra. Information was collected using semi-structured ethnobotanical interviews, and we subsequently made maps using Arc-View 8.0 program to determine the area of use of each taxon. Each map was then compared with the bioclimatic and linguistic map of Navarra, using the soil and ethnographic data for the region, and with other ethnobotanical and ethnopharmacological studies carried out in Europe. RESULTS: The results clearly show that ecological and cultural factors influence the selection of medicinal plants in this region. Climate and substrate are the most important ecological factors that influence the distribution and abundance of plants, which are the biological factors that affect medicinal plant selection. CONCLUSION: The study of edaphological and climatological factors, on the one hand, and culture, on the other, can help us to understand why a plant is replaced by another one for the same purposes, either in the same or in a different area. In many cases, the cultural factor means that the use of a species is more widespread than its ecological distribution. This may also explain the presence of synonyms and polysemies which are useful for discussing ethnopharmacological data

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion

Genetic and biological characterization of a densovirus isolate that affects dengue virus infection

Brevidensoviruses have an encapsidated, single-stranded DNA genome that predominantly has a negative polarity. In recent years, they have received particular attention due to their potential role in the biological control of pathogenic arboviruses and to their unnoticed presence in cell cultures as contaminants. In addition, brevidensoviruses may also be useful as viral vectors. This study describes the first genetic and biological characterization of a mosquito densovirus that was isolated in Brazil; moreover, we examined the phylogenetic relationship between this isolate and the other brevidensoviruses. We further demonstrate that this densovirus has the potential to be used to biologically control dengue virus (DENV) infection with in vitro co-infection experiments. The present study provides evidence that this densovirus isolate is a fast-spreading virus that affects cell growth and DENV infection