320 research outputs found

    Improving the Specificity of EEG for Diagnosing Alzheimer's Disease

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    Objective. EEG has great potential as a cost-effective screening tool for Alzheimer's disease (AD). However, the specificity of EEG is not yet sufficient to be used in clinical practice. In an earlier study, we presented preliminary results suggesting improved specificity of EEG to early stages of Alzheimer's disease. The key to this improvement is a new method for extracting sparse oscillatory events from EEG signals in the time-frequency domain. Here we provide a more detailed analysis, demonstrating improved EEG specificity for clinical screening of MCI (mild cognitive impairment) patients. Methods. EEG data was recorded of MCI patients and age-matched control subjects, in rest condition with eyes closed. EEG frequency bands of interest were θ (3.5–7.5 Hz), α1 (7.5–9.5 Hz), α2 (9.5–12.5 Hz), and β (12.5–25 Hz). The EEG signals were transformed in the time-frequency domain using complex Morlet wavelets; the resulting time-frequency maps are represented by sparse bump models. Results. Enhanced EEG power in the θ range is more easily detected through sparse bump modeling; this phenomenon explains the improved EEG specificity obtained in our previous studies. Conclusions. Sparse bump modeling yields informative features in EEG signal. These features increase the specificity of EEG for diagnosing AD

    Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury

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    INTRODUCTION: Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO. METHODS: After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion. RESULTS: Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 > or = 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO. CONCLUSIONS: ET-1 may therefore be involved in mediating the response to INO

    Seasonality in diabetes in Yaounde, Cameroon: a relation with precipitation and temperature

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    Abstract Background Diabetes is a growing health concern in developing countries, with Cameroon population having an estimated 6% affected. Of note, hospital attendees appear to be increasing all over the country, with fluctuating numbers throughout the annual calendar. The aim of the study was to investigate the relationship between diabete hospitalization admission rates and climate variations in Yaounde. Methods A retrospectively designed study was conducted in four health facilities of Yaounde (Central Hospital, University teaching hospital, Biyem-Assi and Djoungolo District Hospitals), using medical records from 2000 to 2008. A relationship between diabetes (newly diagnosed diabetes patients or decompensated diabetics) hospitalization admissions and climate variations was determined using the “2000–2008” national meteorological database (precipitation and temperature). Results The monthly medians of precipitation and temperature were 154mm and 25 °C, respectively. The month of October received 239mm of precipitation. The monthly medians of diabetic admissions rates (newly diagnosed or decompensated diabetes patients) were 262 and 72 respectively. October received 366 newly diagnosed diabetics and 99 decompensated diabetics. Interestingly, diabetic hospitalization admissions rates were higher during the rainy (51 %, 1633/3232) than the dry season, though the difference was non-significant. The wettest month (October) reported the highest cases (10 %, 336/3232) corresponding to the month with the highest precipitation level (239mm). Diabetes hospitalization admissions rates varied across health facilities [from 6 % (189/3232) in 2000 to 15 % (474/3232) in 2008]. Conclusion Diabetes is an important epidemiological disease in the city of Yaounde. The variation in the prevalence of diabetes is almost superimposed to that of precipitation; and the prevalence seems increasing during raining seasons in Yaoundé

    Expression and knockdown of zebrafish folliculin suggests requirement for embryonic brain morphogenesis.

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    BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited familial cancer syndrome characterised by the development of benign skin fibrofolliculomas, multiple lung and kidney cysts, spontaneous pneumothorax and susceptibility to renal cell carcinoma. BHD is caused by mutations in the gene encoding Folliculin (FLCN). Little is known about what FLCN does in a healthy individual and how best to treat those with BHD. As a first approach to developing a vertebrate model for BHD we aimed to identify the temporal and spatial expression of flcn transcripts in the developing zebrafish embryo. To gain insights into the function of flcn in a whole organism system we generated a loss of function model of flcn by the use of morpholino knockdown in zebrafish. RESULTS: flcn is expressed broadly and upregulated in the fin bud, somites, eye and proliferative regions of the brain of the Long-pec stage zebrafish embryos. Together with knockdown phenotypes, expression analysis suggest involvement of flcn in zebrafish embryonic brain development. We have utilised the zFucci system, an in vivo, whole organism cell cycle assay to study the potential role of flcn in brain development. We found that at the 18 somite stage there was a significant drop in cells in the S-M phase of the cell cycle in flcn morpholino injected embryos with a corresponding increase of cells in the G1 phase. This was particularly evident in the brain, retina and somites of the embryo. Timelapse analysis of the head region of flcn morpholino injected and mismatch control embryos shows the temporal dynamics of cell cycle misregulation during development. CONCLUSIONS: In conclusion we show that zebrafish flcn is expressed in a non-uniform manner and is likely required for the maintenance of correct cell cycle regulation during embryonic development. We demonstrate the utilisation of the zFucci system in testing the role of flcn in cell proliferation and suggest a function for flcn in regulating cell proliferation in vertebrate embryonic brain development.Funding for this project was provided by the Myrovlytis Trust and a KWF travel grant to Monique Luijten.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12861-016-0119-

    Relevance of a mobile internet platform for capturing inter- and intrasubject variabilities in circadian coordination during daily routine : pilot study

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    Background: Experimental and epidemiologic studies have shown that circadian clocks disruption can play an important role in the development of cancer and metabolic diseases. The cellular clocks outside the brain are effectively coordinated by the body temperature rhythm. We hypothesized that concurrent measurements of body temperature and rest-activity rhythms would assess circadian clocks coordination in individual patients, thus enabling the integration of biological rhythms into precision medicine. Objective The objective was to evaluate the circadian clocks’ coordination in healthy subjects and patients through simultaneous measurements of rest-activity and body temperature rhythms. Methods Non-invasive real-time measurements of rest-activity and chest temperature rhythms were recorded during the subject’s daily life, using a dedicated new mobile e-health platform (PiCADo). It involved a chest sensor that jointly measured accelerations, 3D-orientation and skin surface temperature every 1-5 min, and relayed them out to a mobile gateway via Bluetooth-Low-Energy. The gateway tele-transmitted all stored data to a server via GPRS every 24 h. The technical capabilities of PiCADo were validated in 55 healthy subjects and 12 cancer patients, whose rhythms were e-monitored during their daily routine for 3-30 days. Spectral analyses enabled to compute rhythm parameters values, with their 90% confidence limits, and their dynamics in each subject. Results All the individuals displayed a dominant circadian rhythm in activity with maxima occurring from 12:09 to 20:25. This was not the case for the dominant temperature period, which clustered around 24 h for 51 out of 67 subjects (76%), and around 12 h for 13 others (19%). Statistically significant sex- and age- related differences in circadian coordination were identified in the non-cancerous subjects, based upon the range of variations in temperature rhythm amplitudes, maxima (acrophases), and phase relations with rest-activity. The circadian acrophase of chest temperature was located at night for the majority of people, but it occurred at daytime for 26% (14/55) of the non-cancerous people and 33% (4/12) of the cancer patients, hence supporting important inter-subject differences in circadian coordination. Sex, age and cancer significantly impacted on the circadian coordination of both rhythms, based on their phase relationships. Conclusions Complementing rest-activity with chest temperature circadian e-monitoring revealed striking inter-subject differences regarding human circadian clocks coordination and timing during daily routine. To further delineate the clinical importance of such finding, the PiCADo platform is currently applied for both the assessment of health effects resulting from atypical work schedules, and the identification of the key determinants of circadian disruption in cancer patients

    Proline and COMT Status Affect Visual Connectivity in Children with 22q11.2 Deletion Syndrome

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    Background Individuals with the 22q11.2 deletion syndrome (22q11DS) are at increased risk for schizophrenia and Autism Spectrum Disorders (ASDs). Given the prevalence of visual processing deficits in these three disorders, a causal relationship between genes in the deleted region of chromosome 22 and visual processing is likely. Therefore, 22q11DS may represent a unique model to understand the neurobiology of visual processing deficits related with ASD and psychosis. Methodology We measured Event-Related Potentials (ERPs) during a texture segregation task in 58 children with 22q11DS and 100 age-matched controls. The C1 component was used to index afferent activity of visual cortex area V1; the texture negativity wave provided a measure for the integrity of recurrent connections in the visual cortical system. COMT genotype and plasma proline levels were assessed in 22q11DS individuals. Principal Findings Children with 22q11DS showed enhanced feedforward activity starting from 70 ms after visual presentation. ERP activity related to visual feedback activity was reduced in the 22q11DS group, which was seen as less texture negativity around 150 ms post presentation. Within the 22q11DS group we further demonstrated an association between high plasma proline levels and aberrant feedback/feedforward ratios, which was moderated by the COMT158 genotype. Conclusions These findings confirm the presence of early visual processing deficits in 22q11DS. We discuss these in terms of dysfunctional synaptic plasticity in early visual processing areas, possibly associated with deviant dopaminergic and glutamatergic transmission. As such, our findings may serve as a promising biomarker related to the development of schizophrenia among 22q11DS individuals
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