Structural brain network abnormalities and the probability of seizure recurrence after epilepsy surgery

OBJECTIVE: We assessed preoperative structural brain networks and clinical characteristics of patients with drug-resistant temporal lobe epilepsy (TLE) to identify correlates of postsurgical seizure recurrences. METHODS: We examined data from 51 patients with TLE who underwent anterior temporal lobe resection (ATLR) and 29 healthy controls. For each patient, using the preoperative structural, diffusion, and postoperative structural MRI, we generated 2 networks: presurgery network and surgically spared network. Standardizing these networks with respect to controls, we determined the number of abnormal nodes before surgery and expected to be spared by surgery. We incorporated these 2 abnormality measures and 13 commonly acquired clinical data from each patient into a robust machine learning framework to estimate patient-specific chances of seizures persisting after surgery. RESULTS: Patients with more abnormal nodes had a lower chance of complete seizure freedom at 1 year and, even if seizure-free at 1 year, were more likely to relapse within 5 years. The number of abnormal nodes was greater and their locations more widespread in the surgically spared networks of patients with poor outcome than in patients with good outcome. We achieved an area under the curve of 0.84 ± 0.06 and specificity of 0.89 ± 0.09 in predicting unsuccessful seizure outcomes (International League Against Epilepsy [ILAE] 3–5) as opposed to complete seizure freedom (ILAE 1) at 1 year. Moreover, the model-predicted likelihood of seizure relapse was significantly correlated with the grade of surgical outcome at year 1 and associated with relapses up to 5 years after surgery. CONCLUSION: Node abnormality offers a personalized, noninvasive marker that can be combined with clinical data to better estimate the chances of seizure freedom at 1 year and subsequent relapse up to 5 years after ATLR. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that node abnormality predicts postsurgical seizure recurrence

Frutapin, a lectin from Artocarpus incisa (breadfruit): cloning, expression and molecular insights

Artocarpus incisa (breadfruit) seeds contain three different lectins (Frutalin, Frutapin and Frutackin) with distinct carbohydrate specificities. The most abundant lectin is Frutalin, an α-D-galactose-specific carbohydrate-binding glycoprotein with antitumour properties and potential for tumour biomarker discovery as already reported. Frutapin (FTP) is the second most abundant, but proved difficult to purify with very low yields and contamination with Frutalin frustrating its characterization. Here, we report for the first time high-level production and isolation of biologically-active recombinant FTP in E. coli BL21, optimizing conditions with the best set yielding >40 mg/L culture of soluble active FTP. The minimal concentration for agglutination of red blood cells was 62.5 µg/mL of FTP, a process effectively inhibited by mannose. Apo-FTP, FTP-mannose and FTP-glucose crystals were obtained and diffracted X-rays to a resolution of 1.58 (P212121), 1.70 (P3121) and 1.60 (P3121) Å, respectively. The best solution showed four monomers per asymmetric unit. Molecular Dynamics simulation suggested FTP displays higher affinity for mannose than glucose. Cell studies revealed FTP was non-cytotoxic to cultured mouse fibroblast 3T3 cells below 0.5 mg/mL and also capable of stimulating cell migration at 50 µg/mL. In conclusion, our optimized expression system allowed high amounts of correctly-folded soluble FTP to be isolated. This recombinant bioactive lectin will now be tested in future studies for therapeutic potential; for example, in wound healing and tissue regeneration

Photosynthesis by six portuguese maize cultivars during drought stress and recovery

Photosynthesis, chlorophyll fluorescence and leaf water parameters were measured in six Portuguese maize (Zea mays L.) cultivars during and following a period of drought stress. The leaf relative water content (RWC) responded differently among cultivars but, except for cultivar PB369, recovered close to initial values after watering was restored. Photosynthetic rate and stomatal conductance decreased with drought but more slowly in cultivars PB269 and PB260 than in cultivars AD3R, PB64, PB304 and PB369. Water use efficiency (WUE) decreased during the water stress treatment although with cultivar PB260 the decrease was marked only when the RWC fell below 40%. Recovery of WUE was seen with all cultivars except PB369. The maximum quantum efficiency of photosystem II, the photochemical quenching coefficient, the electron transport rate in PSII and the estimated functional plastoquinone pool tended to decrease with drought, while the non -photochemical quenching coefficient increased. The parameters estimated from chlorophyll fluorescence did not recover in PB369, during re - watering. The results show that PB260 and PB269 were the most tolerant and PB369 was the least tolerant cultivars to water stress. The variation found amongst the cultivars tested suggests the existence of valuable genetic resources for crop improvement in relation to drought tolerance

HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways

BACKGROUND: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. METHODS: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. RESULTS: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. CONCLUSIONS: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior

Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio

Health workers' perspectives on asthma care coordination between primary and specialised healthcare in the COVID-19 pandemic: a protocol for a qualitative study in Ecuador and Brazil.

INTRODUCTION: Asthma is a common long-term disorder and strategies to improve asthma control are still a challenge. Integrated delivery of health systems is critical for effective asthma care: there is limited information on experiences of care coordination for asthma from Latin America, especially on perspectives of health personnel and in the context of the COVID-19 pandemic. METHODS AND ANALYSIS: This protocol details a qualitative approach to analyse health workers' perspectives of healthcare coordination for asthma control during COVID-19 pandemic in Ecuador and Brazil, at primary and specialised levels, through in-depth semistructured interviews using a video communications platform. The analysis will identify knowledge and perspectives based on coordination of clinical information, clinical management and administrative coordination. Theoretical sampling will be used to obtain approximately equal numbers of women and men within each level of healthcare; data saturation will be used to determine sample size. Transcripts will be analysed using content-coding procedures to mark quotations related to major topics and subthemes included in the interview guide, and narrative analysis will be based on a theoretical framework for healthcare coordination to identify new themes and subthemes. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committees of Hospital General Docente Calderón, Quito, Ecuador; and Universidade Federal da Bahia, Salvador, Brazil. The findings of this study will be disseminated through peer-reviewed articles, conference presentations and condensed summaries for key stakeholders and partners

One Health: The global challenge of epidemic and endemic leishmaniasis

'One Health' proposes the unification of medical and veterinary sciences with the establishment of collaborative ventures in clinical care, surveillance and control of cross-species disease, education, and research into disease pathogenesis, diagnosis, therapy and vaccination. The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes ('environmental health') such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL) and zoonotic visceral leishmaniasis (ZVL). The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming