A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson’s Disease

Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7 % in 70 % of the patients.Centro de Investigación Biomédica en RedDepto. de Psicología Experimental, Procesos Cognitivos y LogopediaDepto. de Radiología, Rehabilitación y FisioterapiaFac. de PsicologíaFac. de MedicinaTRUEpu

Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy

BACKGROUND: To evaluate the clinical outcome of primary endonasal laser assisted dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser. METHODS: We retrospectively reviewed all primary ENL-DCRs performed within a period of twelve months by the same combined Ophthalmology and Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main outcome measure for success was resolution or significant improvement of epiphora. Details of surgery, intraoperative and postoperative complications, as well as pathology associated with failure were also studied. Patients were followed up for at least 12 months. RESULTS: A total of 41 consecutive ENL-DCRs on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All patients had bicanalicular silicone intubation for at least 4 months. The success rate at 12 months postoperatively was 78.1%. Pathology associated with failure included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis (2.4%). No significant intra-operative complications were recorded. CONCLUSION: The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe and efficient primary procedure for the treatment of nasolacrimal duct obstruction

Evaluation of arterial anatomy in congenital clubfoot with color doppler ultrasound

OBJECTIVE: This investigation intended to evaluate anterior and posterior tibial arteries at the ankle joint level in congenital clubfoot, by using color Doppler ultrasound (CDU). MATERIAL AND METHOD: Twenty patients with idiopathic clubfoot were selected, from which 18 had unilateral involvement and two had bilateral involvement. Of the 18 patients with unilateral clubfoot, 16 went through surgical treatment and the other two were submitted to conservative treatment with serial casting. Of the bilateral cases, one patient was treated surgically and the other was treated with serial casting. All patients were clinically and radiographically assessed. We used the functional rating as described by Lehman. Then, CDU was applied bilaterally at the ankle joint level, trying to identify both posterior and anterior tibial arteries. RESULTS: In our present series of 20 cases with idiopathic clubfoot, in just one patient we could not identify the anterior tibial artery at the ankle joint level. In 12 patients who have had their arterial flow speeds and diameters measured by UDC, a positive correlation was found between functional level and anterior tibial artery diameter. No statistically significant differences were found between both flow speed and diameter of anterior tibial artery of the normal side, when compared to the affected side (in patients with unilateral disease). CONCLUSION: In our sample, we could not find any significant differences in arterial morphology and flow speed between the normal and the affected side. Furthermore, we noticed that the better the clinical result of clubfoot correction, the larger the diameter of anterior tibial artery in affected feet.OBJETIVO: Avaliação ultrassonográfica das artérias tibial anterior e posterior no pé torto congênito (PTC). MATERIAL E MÉTODO: Foram incluídos 20 pacientes portadores de PTC idiopático compreendendo 18 casos unilaterais e dois bilaterais, sendo que 17 pacientes foram submetidos a tratamento cirúrgico e três a tratamento conservador. Todos os pacientes apresentavam pés plantígrados e foram submetidos à avaliação clínica e radiográfica, seguido pelo exame de ultrassom Doppler colorido (UDC), visando a identificação das artérias tibiais anterior e posterior na altura do tornozelo. O nível funcional foi classificado pelos critérios de Lehman. RESULTADOS: Nesta série de 20 pacientes, somente em um não foi identificada a artéria tibial anterior. Nos 12 pacientes submetidos à mensuração de fluxo e calibre pelo UDC, foi encontrada uma correlação positiva entre o grau funcional do PTC e o calibre da artéria tibial anterior. Não houve redução estatisticamente significante entre o fluxo e calibre da artéria tibial anterior do lado normal em comparação com o lado alterado (nos casos de doença unilateral). CONCLUSÕES: Não houve alteração significativa da morfologia e fluxo arterial quando comparamos os lados afetado e normal. Além disso, quanto melhor o resultado clínico da correção do PTC, maior foi o calibre da artéria tibial anterior.UNIFESP Departamento de Ortopedia e TraumatologiaUNIFESP, Depto. de Ortopedia e TraumatologiaSciEL

The Population Structure of Glossina palpalis gambiensis from Island and Continental Locations in Coastal Guinea

Guinea is the country with the highest prevalence of sleeping sickness in West Africa, and we undertook a population genetics analysis there of the most dangerous tsetse fly species of West Africa, Glossina palpalis gambiensis. Our aims were to estimate effective population size and the degree of isolation between coastal sites on the mainland of Guinea (including Dubréka, a highly prevalent sleeping sickness focus) and Loos Islands in order to get the most possible accurate vision of feasibility and sustainability of anti-tsetse strategies of these sites. We found very low migration rates of tsetse between sites except between those situated in the Dubréka area, which seems to contain a widely distributed panmictic tsetse population (i.e. a population where mating occurs at random). Effective population sizes on Loos islands estimated with various techniques all converged to surprisingly small values. These values might be explained by a recent decrease in tsetse numbers on Kassa Island due to bauxite mining activities. But on the other sites, other explanations have to be found, including possible variance in reproductive success. Our genetic results suggest that different control strategies should be advised on the mainland (reduction in tsetse densities, no elimination) compared to the islands (total elimination feasible). This approach could be extended to many areas where vector control of Human and Animal Trypanosomoses is contemplated

Use of AFLP and RAPD molecular genetic markers and cytogenetic analysis to explore relationships among taxa of the Patagonian Bromus setifolius complex

Bromus setifolius var. pictus (Hook) Skottsb., B. setifolius var. setifolius Presl. and B.setifolius var. brevifolius Ness are three native Patagonian taxa in the section Pnigma Dumort of the genus Bromus L. AFLP and RAPD analysis, in conjunction with genetic distance measurements and statistical techniques, revealed variation within this group and indicated that B. setifolius var. brevifolius was closely related to B. setifolius var. pictus, with both taxa being more distantly related to B. setifolius var. setifolius. Cytogenetic analysis confirmed the chromosomal number of B. setifolius var. pictus (2n = 70) and B. setifolius var. setifolius (2n = 28) and showed for the first time that B. setifolius var. brevifolius had 2n = 70. The combination of molecular genetic and cytogenetic evidence supported a species status for two of the three taxa and suggested hypotheses for the evolutionary origin of these complex taxa. Species status was also indicated for B. setifolius var. setifolius. Based on these findings, we suggest that B. setifolius var. pictus be referred to as B. pictus Hook var. pictus, and B. setifolius var brevifolius as B. pictus Hook var brevifolius. The correlation between AFLP diversity and variation in ecological parameters suggested that this marker system could be used to assess breeding progress and to monitor the domestication of Patagonian Bromus species for agronomic use

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development

Dengue Virus Infection of the Aedes aegypti Salivary Gland and Chemosensory Apparatus Induces Genes that Modulate Infection and Blood-Feeding Behavior

The female Aedes aegypti salivary gland plays a pivotal role in bloodmeal acquisition and reproduction, and thereby dengue virus (DENV) transmission. It produces numerous immune factors, as well as immune-modulatory, vasodilatory, and anti-coagulant molecules that facilitate blood-feeding. To assess the impact of DENV infection on salivary gland physiology and function, we performed a comparative genome-wide microarray analysis of the naïve and DENV infection-responsive A. aegypti salivary gland transcriptomes. DENV infection resulted in the regulation of 147 transcripts that represented a variety of functional classes, including several that are essential for virus transmission, such as immunity, blood-feeding, and host-seeking. RNAi-mediated gene silencing of three DENV infection-responsive genes - a cathepsin B, a putative cystatin, and a hypothetical ankyrin repeat-containing protein - significantly modulated DENV replication in the salivary gland. Furthermore, silencing of two DENV infection-responsive odorant-binding protein genes (OBPs) resulted in an overall compromise in blood acquisition from a single host by increasing the time for initiation of probing and the probing time before a successful bloodmeal. We also show that DENV established an extensive infection in the mosquito's main olfactory organs, the antennae, which resulted in changes of the transcript abundance of key host-seeking genes. DENV infection, however, did not significantly impact probing initiation or probing times in our laboratory infection system. Here we show for the first time that the mosquito salivary gland mounts responses to suppress DENV which, in turn, modulates the expression of chemosensory-related genes that regulate feeding behavior. These reciprocal interactions may have the potential to affect DENV transmission between humans

Detection and elimination of cellular bottlenecks in protein-producing yeasts

Yeasts are efficient cell factories and are commonly used for the production of recombinant proteins for biopharmaceutical and industrial purposes. For such products high levels of correctly folded proteins are needed, which sometimes requires improvement and engineering of the expression system. The article summarizes major breakthroughs that led to the efficient use of yeasts as production platforms and reviews bottlenecks occurring during protein production. Special focus is given to the metabolic impact of protein production. Furthermore, strategies that were shown to enhance secretion of recombinant proteins in different yeast species are presented