Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

INTRODUCTION: Markers of low-grade peripheral inflammation have been reported amongst people with epilepsy. The mechanisms underlying this phenomenon are unknown. We attempted to characterize peripheral immune cells and their activation status in people with temporal lobe epilepsy (TLE) and healthy controls. METHODS AND RESULTS: Twenty people with TLE and 19 controls were recruited, and peripheral blood lymphocyte and monocyte subsets evaluated ex vivo by multi-color flow cytometry. People with TLE had higher expression of HLA-DR, CD69, CTLA-4, CD25, IL-23R, IFN-γ, TNF and IL-17 in CD4(+) lymphocytes than controls. Granzyme A, CTLA-4, IL-23R and IL-17 expression was also elevated in CD8(+) T cells from people with TLE. Frequency of HLA-DR in CD19(+) B cells and regulatory T cells CD4(+)CD25(+)Foxp3(+) producing IL-10 was higher in TLE when compared with controls. A negative correlation between CD4(+) expressing co-stimulatory molecules (CD69, CD25 and CTLA-4) with age at onset of seizures was found. The frequency of CD4(+)CD25(+)Foxp3(+) cells was also positively correlated with age at onset of seizures. CONCLUSION: Immune cells of people with TLE show an activation profile, mainly in effector T cells, in line with the low-grade peripheral inflammation

A dysflagellar mutant of Leishmania (Viannia) braziliensis isolated from a cutaneous leishmaniasis patient

<p>Abstract</p> <p>Background</p> <p>Parasites of the <it>Leishmania </it>genus alternate between the flagellated extracellular promastigote stage and intracellular amastigotes. Here we report the characterization of a <it>Leishmania </it>isolate, obtained from a cutaneous leishmaniasis patient, which presents peculiar morphological features.</p> <p>Methods</p> <p>The parasite was cultured <it>in vitro </it>and characterized morphologically using optical and electron microscopy. Identification was performed based on monoclonal antibodies and internal ribosomal spacer typing. <it>In vitro </it>macrophage cultures, murine experimental models and sand fly infections were used to evaluate infectivity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>The isolate was identified as <it>Leishmania </it>(<it>Viannia</it>) <it>braziliensis</it>. In the atypical promastigotes grown in culture, a short flagellum surrounded or interrupted by a protuberance of disorganized material was observed. A normal axoneme was present close to the basal body but without elongation much further outside the flagellar pocket. A disorganized swelling at the precocious end of the axoneme coincided with the lack of a paraflagellar rod structure. The isolate was able to infect macrophages <it>in vitro</it>, induce lesions in BALB/c mice and infect <it>Lutzomyia longipalpis</it>.</p> <p>Conclusions</p> <p>Notwithstanding the lack of an extracellular flagellum, this isolate infects macrophages <it>in vitro </it>and produces lesions when inoculated into mice. Moreover, it is able to colonize phlebotomine sand flies. Considering the importance attributed to the flagellum in the successful infection and survival of <it>Leishmania </it>in the insect midgut and in the invasion of macrophages, these findings may bring new light into the infectious mechanisms of <it>L</it>. (<it>V</it>.) <it>braziliensis</it>.</p

Green Infrastructure in the Space of Flows: An Urban Metabolism

Recent research demonstrates that urban metabolism studies hold ample scope for informing more sustainable urban planning and design. The assessment of the resource flows that are required to sustain the growth and maintenance of cities can allow gaining a clear picture of how cities operate to comply with environmental performance standards and to ensure that both human and ecosystem health are preserved. Green infrastructure (GI) plays a key role in enhancing both cities’ environmental performance and health. For example, GI interventions mitigate the Urban Heat Island effect (improved thermal comfort), reduce particulate matter concentration (healthier air quality), and sequestrate and store atmospheric carbon (climate change mitigation). Research on ecosystem services and the application of the concept in urban planning provides a growing evidence base that an understanding of provisioning and regulating services can facilitate more environmentally informed GI planning and design. The contribution of GI in enhancing human health and psychological wellbeing is also evidenced in recent studies valuing both material and immaterial benefits provided by urban ecosystems, including cultural ecosystem services. Therefore, the use of ecosystem service frameworks can help reveal and quantify the role of GI in fostering both urban environmental quality and the wellbeing of human populations. However, there remains little discussion of how health and wellbeing aspects can be integrated with environmental performance objectives. In this chapter, urban metabolism thinking is proposed as a way forward, providing analytical tools to inform environmentally-optimized strategies across the urban scales. Opportunities to foster integrated urban metabolism approaches that can inform more holistic GI planning are discussed. Finally, future research avenues to incorporate the multiple dimensions of human health and wellbeing into urban metabolism thinking are highlighted

Evaluation of zona pellucida birefringence intensity during in vitro maturation of oocytes from stimulated cycles

Background: This study evaluated whether there is a relationship between the zona pellucida birefringence (ZP-BF) intensity and the nuclear (NM) and cytoplasmic (CM) in vitro maturation of human oocytes from stimulated cycles.Results: The ZP-BF was evaluated under an inverted microscope with a polarizing optical system and was scored as high/positive (when the ZP image presented a uniform and intense birefringence) or low/negative (when the image presented moderate and heterogeneous birefringence). CM was analyzed by evaluating the distribution of cortical granules (CGs) throughout the ooplasm by immunofluorescence staining. CM was classified as: complete, when CG was localized in the periphery; incomplete, when oocytes presented a cluster of CGs in the center; or in transition, when oocytes had both in clusters throughout cytoplasm and distributed in a layer in the cytoplasm periphery Nuclear maturation: From a total of 83 germinal vesicle (GV) stage oocytes, 58 of oocytes (69.9%) reached NM at the metaphase II stage. From these 58 oocytes matured in vitro, the high/positively scoring ZP-BF was presented in 82.7% of oocytes at the GV stage, in 75.8% of oocytes when at the metaphase I, and in 82.7% when oocytes reached MII. No relationship was observed between NM and ZP-BF positive/negative scores (P = 0.55). These variables had a low Pearson's correlation coefficient (r = 0.081). Cytoplasmic maturation: A total of 85 in vitro-matured MII oocytes were fixed for CM evaluation. Forty-nine oocytes of them (57.6%) showed the complete CM, 30 (61.2%) presented a high/positively scoring ZP-BF and 19 (38.8%) had a low/negatively scoring ZP-BF. From 36 oocytes (42.3%) with incomplete CM, 18 (50%) presented a high/positively scoring ZPBF and 18 (50%) had a low/negatively scoring ZP-BF. No relationship was observed between CM and ZP-BF positive/negative scores (P = 0.42). These variables had a low Pearson's correlation coefficient (r = 0.11).Conclusions: The current study demonstrated an absence of relationship between ZP-BF high/positive or low/negative score and nuclear and cytoplasmic in vitro maturation of oocytes from stimulation cycles

High-Fat Diet Induces Apoptosis of Hypothalamic Neurons

Consumption of dietary fats is amongst the most important environmental factors leading to obesity. In rodents, the consumption of fat-rich diets blunts leptin and insulin anorexigenic signaling in the hypothalamus by a mechanism dependent on the in situ activation of inflammation. Since inflammatory signal transduction can lead to the activation of apoptotic signaling pathways, we evaluated the effect of high-fat feeding on the induction of apoptosis of hypothalamic cells. Here, we show that consumption of dietary fats induce apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. This effect is dependent upon diet composition, and not on caloric intake, since pair-feeding is not sufficient to reduce the expression of apoptotic markers. The presence of an intact TLR4 receptor, protects cells from further apoptotic signals. In diet-induced inflammation of the hypothalamus, TLR4 exerts a dual function, on one side activating pro-inflammatory pathways that play a central role in the development of resistance to leptin and insulin, and on the other side restraining further damage by controlling the apoptotic activity