Hemato-immunological responses of Heros severus fed diets supplemented with different levels of Dunaliella salina.

In this study, the effects of oral administration of different levels of Dunaliella salina (a natural ß-carotene source) on growth parameters, immunological and hematological indices, as well as skin carotenoids, of Heros severus were investigated. One hundred and eighty H. severus weighing 27 ± 0.5 g were divided randomly into four groups in triplicate (15 fish in each replicate). Groups 1-4 received food supplemented with 0, 50, 100 and 200 mg kg⁻¹ D. salina powder, respectively. After 6 weeks, the growth parameters were compared among the groups. Blood samples were taken from each group, and hematological parameters including red blood cell count (RBC), white blood cell count (WBC), hematocrit (PCV), hemoglobin (Hb) and immunological indices (serum and mucus lysozyme and bactericidal activity, resistance against Aeromonas hydrophila infection) as well as carotenoid content of skin were evaluated. Results showed that some growth indices increased significantly in fish fed with 100 and 200 mg kg⁻¹ D. salina-supplemented food (P < 0.05). Although serum lysozyme activity was increased in fish fed with food supplemented with 100 and 200 mg kg⁻¹ D. salina (P < 0.05), no significant change was observed in serum and mucus bactericidal activity and mucus lysozyme activity among the groups (P > 0.05). Most of the hematological parameters such as WBC, RBC, PCV and Hb significantly increased in D. salina-treated fish compared with controls (P < 0.05). Mortality induced after challenge with A. hydrophila in 200 mg kg⁻¹ D. salina-treated fish was 36.67 %, which significantly decreased compared with control (P < 0.05). Skin carotenoid content in all D. salina treatments was statistically higher than that of control (P < 0.05). Conclusively, D. salina as a food additive can affect positively the growth, immunological and hematological parameters of H. severus.

Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept.

PURPOSE: To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with (90)Y-loaded glass microspheres (TheraSphere®). METHODS: TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). RESULTS: The response rate was 78.8%. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100% and overall accuracy of 90%. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4%), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (10-16 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83% and overall accuracy of 97%. CONCLUSION: Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.

Accelerometer-based fetal movement detection.

Monitoring fetal wellbeing is a compelling problem in modern obstetrics. Clinicians have become increasingly aware of the link between fetal activity (movement), well-being, and later developmental outcome. We have recently developed an ambulatory accelerometer-based fetal activity monitor (AFAM) to record 24-hour fetal movement. Using this system, we aim at developing signal processing methods to automatically detect and quantitatively characterize fetal movements. The first step in this direction is to test the performance of the accelerometer in detecting fetal movement against real-time ultrasound imaging (taken as the gold standard). This paper reports first results of this performance analysis.

Kalman filter-based time-varying cortical connectivity analysis of newborn EEG.

Multivariate Granger causality in the time-frequency domain as a representation of time-varying cortical connectivity in the brain has been investigated for the adult case. This is, however, not the case in newborns as the nature of the transient changes in the newborn EEG is different from that of adults. This paper aims to evaluate the performance of the time-varying versions of the two popular Granger causality measures, namely Partial Directed Coherence (PDC) and direct Directed Transfer Function (dDTF). The parameters of the time-varying AR, that models the inter-channel interactions, are estimated using Dual Extended Kalman Filter (DEKF) as it accounts for both non-stationarity and non-linearity behaviors of the EEG. Using simulated data, we show that fast changing cortical connectivity between channels can be measured more accurately using the time-varying PDC. The performance of the time-varying PDC is also tested on a neonatal EEG exhibiting seizure.

A nonlinear model of newborn EEG with nonstationary inputs.

Newborn EEG is a complex multiple channel signal that displays nonstationary and nonlinear characteristics. Recent studies have focussed on characterizing the manifestation of seizure on the EEG for the purpose of automated seizure detection. This paper describes a novel model of newborn EEG that can be used to improve seizure detection algorithms. The new model is based on a nonlinear dynamic system; the Duffing oscillator. The Duffing oscillator is driven by a nonstationary impulse train to simulate newborn EEG seizure and white Gaussian noise to simulate newborn EEG background. The use of a nonlinear dynamic system reduces the number of parameters required in the model and produces more realistic, life-like EEG compared with existing models. This model was shown to account for 54% of the linear variation in the time domain, for seizure, and 85% of the linear variation in the frequency domain, for background. This constitutes an improvement in combined performance of 6%, with a reduction from 48 to 4 model parameters, compared to an optimized implementation of the best performing existing model.

Transforming scales of measurement of visual acuity at the group level.

AIM: To provide formulae that may be used to transform sample-based estimates of group-level mean and standard deviation of visual acuity (VA) across different scales of measurement. METHODS: We focused on 3 transformations: (1) ETDRS letters - LogMAR (2) Decimal - LogMAR and (3) Snellen - LogMAR. We assumed that logMAR follows a normal distribution in the underlying population and used the empirical asymptotic normal approximation of the joint distribution of average and standard deviation in order to derive formulae for transformation of group-level estimates. We considered that the true population parameters are not known and are to be estimated using data from a sample of patients (which is essentially always the case). We compared estimates obtained with the proposed sample-based approach with those based on a "naïve" approach in which individual-level formulae are used directly for transformation of means and standard deviations at the group-level. RESULTS: Applying formulae that are appropriate for transformations of scales of measurement for data at the individual- (or patient-) level, to transform VA at the group level, can lead to biased estimates of means and standard deviations. In particular, it could lead to underestimation of the average logMAR VA in studies that use decimal VA. Such bias will be greater in magnitude when disease strongly affects VA. CONCLUSIONS: This paper provides formulae that can be easily implemented in standard spreadsheet software programs, and which allow appropriate transformations of group-level estimates of mean and standard deviation of VA across different scales of measurement. These transformations are helpful for performing meta-analyses or for comparisons of results across studies when VA is expressed in different units.

Treatment Target Test Dementia (3TD).

OBJECTIVE: So far goal-oriented therapy in dementia cannot be measured sufficiently. There are no tests that detect a profile of capacities that could describe the targets of training. Thus, it was aimed to develop a test that uncovers a profile of capacities in patients suffering from dementia. METHODS: Three groups of subjects (n = 156), 30 patients suffering from dementia of the Alzheimer type, 28 from depressive disorder and 98 healthy age-comparable controls were included in the study. Building on already existing tests, items were developed to cover intelligence, visuo-spatial abilities, cognitive and social problem solving, emotional and executive abilities. All subjects were investigated with the Training Target Test Dementia (3TD). To calculate convergence validity, the Test for the Early Detection of Dementia from depression (TE4D) and the Beck Depression Inventory were assessed. Descriptively, profiles were calculated. Group differences were studied with the Kruskal-Wallis and the Mann-Whitney-U-test. RESULTS: Characteristic neuropsychological capacity profiles were found within the three groups. Differences between the groups were significant for all subtests. Significantly, the 3TD separated patients with dementia from controls. It reached high sensitivity and acceptable specificity. The convergence validity to the TE4D was significant (r = 0.77). CONCLUSIONS: The capacity profiles detected may allow for specified therapeutic modules to be scheduled. Moreover, the 3TD will be suitable to discriminate between patients suffering from dementia, depression as well as healthy age-comparable controls. For therapeutic improvement, further investigation will be needed to prove its sensitivity.

Combining newborn EEG and HRV information for automatic seizure detection.

We propose a new seizure detection framework based on combination of information extracted from newborn multi-channel electroencephalogram (EEG) and heart rate variability (HRV). Two approaches are investigated for the combination of EEG and HRV, namely; feature fusion and classifier/decision fusion. The feature fusion was performed by concatenating the features vectors extracted from the EEG and the HRV signals while the classifier fusion was accomplished by fusing the independent decisions from individual classifiers of EEG and HRV. Both proposed schemes consist of a sequence of processing steps, namely; preprocessing, feature extraction, feature selection and finally the combination. We have shown that both proposed approaches lead to improved performance of newborn seizure detection compared to either EEG or HRV based seizure detectors.

Detection of neonatal EEG seizure using multichannel matching pursuit.

It is unusual for a newborn to have the classic "tonic-clonic" seizure experienced by adults and older children. Signs of seizure in newborns are either subtle or may become clinically silent. Therefore, the electroencephalogram (EEG) is becoming the most reliable tool for detecting neonatal seizure. Being non-stationary and multicomponent, EEG signals are suitably analyzed using time-frequency (TF) based methods. In this paper, we present a seizure detection method using a new measure based on the matching pursuit (MP) decomposition of EEG data. Signals are represented in the TF domain where seizure structural characteristics are extracted to form a new coherent TF dictionary to be used in the MP decomposition. A new approach to set data-dependent thresholds, used in the seizure detection process, is proposed. To enhance the performance of the detector, the concept of areas of incidence is utilized to determine the geometrical correlation between EEG recording channels.

Quadratic time-frequency distribution selection for seizure detection in the newborn.

Several, recently proposed, newborn EEG seizure detection techniques use quadratic time-frequency distributions (QTFDs) to generate the time-frequency representations (TFRs) at their core. The specific type of QTFD that provides the best discrimination between the TFR of nonseizure and seizure epochs of EEG, however, has yet to be thoroughly investigated. This paper proposes the selection of an optimal QTFD that maximises the the absolute error between seizure and nonseizure QTFDs calculated on a database of newborn EEG. The optimisation procedure is a data driven process that selects the optimal QTFD based on the distribution of the absolute error between nonseizure/nonseizure QTFDs and the seizure/nonseizure QTFDs. Several non-adaptive QTFDs were selected for comparison and those selected were subjected to a restriction on the kernel's volume to ensure that the QTFD can accurately represent the time-frequency distribution of signal energy. The results show that a lag independent or narrowband QTFD such as the modified B distribution provides a QTFD that best highlights the difference in time-frequency signal energy between newborn EEG seizure and nonseizure.

A feature set for EEG seizure detection in the newborn based on seizure and background charactersitics.

This paper presents a set of four features to be used in the detection of seizure in the electroencephalograms (EEGs) of newborns. The features are designed with the aid of recent advances in modelling of the newborn EEG. The performance of the features is analysed with a database of 500 epochs of newborn EEG (250 background/250 seizure). The covariance of the features is also analysed to indicate the redundancy of the feature set. The results show significant differences in the features between seizure and background EEG. The covariance between the features suggests that there is little redundant information between the features.

Multichannel-based newborn EEG seizure detection using time-frequency matched filter.

In recent years, much effort has been made toward developing computerized methods to detect seizures. In adults, the clinical signs of seizures are well defined and easily recognizable. But in newborns, these signs are either subtle or completely absent. For this reason, the electroencephalogram (EEG) has been the most dependable tool used for detecting seizures in newborns. Considering the non-stationary and multicomponent nature of the EEG signals, time-frequency (TF) based methods were found to be very suitable for the analysis of such signals. Using TF representation of EEG signals allows extracting TF signatures that are characteristic of EEG seizures. In this paper we present a TF method for newborn EEG seizure detection using a TF matched filter. The threshold used to distinguish between seizure and non-seizure is data-dependent and is set using the EEG background. Multichannel geometrical correlation, based on a concept of incidence matrix, was utilized to further enhance the performance of the detector.

Self-reported visual impairment and mortality: a French nationwide perspective.

PURPOSE: To estimate the association between self-reported visual impairment and mortality. METHODS: Two national surveys in community and institutionalized populations were combined. First, 2,075 institutions for children with impairments, adults with impairments aged persons, and psychiatric patients were selected randomly. The sample comprised 15,403 subjects of whom 14,603 (94.9%) were interviewed. Second, a random, stratified sample of 21,760 persons living in the community was selected, and 16,945 (77.9%) were interviewed. Types of impairment were identified by face-to-face interviews. Two years later, 14,497 subjects in institutions and 15,648 in the community were revisited. Data on death were obtained from either the National Register or households. Death rates were related to age, gender, and impairment. A logistic regression was performed including impairments, activities of daily living, age, gender, type of residence, and geographical area. RESULTS: Strong, independent associations were found between particular impairments, institutional residence, activities of daily living, age, gender, and risk of death. Associations between mortality and type of impairment could be ranked as follows: motor (OR = 1.235), brain (OR = 1.552), low vision (OR = 1.681), speech (OR = 2.090), visceral (OR = 2.233) and blindness (OR = 2.262). CONCLUSIONS: Self-reported visual impairment is an independent factor associated with mortality.

A matching pursuit-based signal complexity measure for the analysis of newborn EEG.

This paper presents a new relative measure of signal complexity, referred to here as relative structural complexity (RSC), which is based on the matching pursuit (MP) decomposition. By relative, we refer to the fact that this new measure is highly dependent on the decomposition dictionary used by MP. The structural part of the definition points to the fact that this new measure is related to the structure, or composition, of the signal under analysis. After a formal definition, the proposed RSC measure is used in the analysis of newborn electroencephalogram (EEG). To do this, firstly, a time-frequency decomposition dictionary is specifically designed to compactly represent the newborn EEG seizure state using MP. We then show, through the analysis of synthetic and real newborn EEG data, that the relative structural complexity measure can indicate changes in EEG structure as it transitions between the two EEG states; namely seizure and background (non-seizure).

Blindness, low vision, and other handicaps as risk factors attached to institutional residence.

AIMS: To estimate the risk of living in an institution and being visually impaired. METHODS: Two national surveys were pooled: (1) 2075 institutions (for children or adults with handicaps, old people, and psychiatric centres) were selected randomly, in 18 predefined strata, from the French health ministry files. From these institutions, 15 403 subjects were selected randomly and handicap was documented by interview in 14 603 (94.9%) of them; (2) level of handicap was documented in a randomised, stratified sample of 356 208 citizens living in the community; from this sample, 21 760 subjects were further selected at random and 16 945 people were interviewed. Data on handicaps (visual, auditory, speech, brain, visceral, motor, and other) and activities of daily living (ADL) were extracted. The odds ratio (OR) of living in an institution was estimated, using stepwise logistic regressions with age, geographical area, handicaps, and ADL as co-variables. RESULTS: Subjects in institutions, compared to those living at home, were, respectively, more often female (64.3% v 52.4%) and older (68.7 v 38.0 years); they more often had handicaps (ORs: speech, 6.59; brain, 10.17; motor, 8.86; visceral, 3.49; auditory, 2.66; other, 1.53); and were less often able to perform their ADL (46.2% v 97.1%) without assistance. Below 80 years, blind people were more often in institutions (ORs 0.239 to 0.306); whereas in older people the association was reversed (OR: 3.277). Low vision was always significantly associated with institutional residence (ORs from 0.262 to 0.752). CONCLUSION: Visual handicap was associated with institutional residence. The link persisted after adjustment for known confounding factors.

Putative membrane receptor for 1,25(OH)2 vitamin D3 in human mineralized tissues during prenatal development.

The calciotropic hormone, 1,25(OH)2vitamin D3[1,25(OH)2D3], controls the formation of dental and bone mineralized tissues. The role of nuclear 1,25(OH)2D3 receptor has been extensively studied in the diverse secretory cells, i.e., osteoblasts, chondrocytes, ameloblasts, and odontoblasts. A nongenomic pathway also has been characterized and related to the interactions of 1,25(OH)2D3 ligand with a putative cell membrane receptor. This recognition moiety called 1,25(OH)2vitamin D3 membrane-associated, rapid-response steroid-binding [1,25D3-MARRS] protein is investigated here in the craniofacial skeleton of human embryos and fetuses. Immunolocalization using a specific Ab099 against chick intestinal basolateral 1,25D3-MARRS protein was performed. The data show a complementary expression pattern of the membrane receptor when compared with published data on the nuclear receptor, notably during amelogenesis. In mandible, membrane receptors for 1,25(OH)2D3 were identified in the heterogenous bone cell population, including osteoblasts and osteoclasts. Differential 1,25D3-MARRS protein levels were observed in distinct developmental stages and anatomical sites of tooth and bone, suggesting the existence of cross-talk between local factors and 1,25D3-MARRS protein expression.

Msx1 is a regulator of bone formation during development and postnatal growth: in vivo investigations in a transgenic mouse model.

The present study is devoted to Msx1 distribution and function from birth to 15 months, events and periods still unexplored in vivo using Msx1 knock in transgenic mice. The study is focused on the mandible, as an exemplary model system for Msx1-dependent neural crest-derived skeletal unit. The transgenic line enabled study of morphological abnormalities in Msx1 null mutation mice and Msx1 protein expression in Msx1+/- heterozygous mice. In Msx1 null mutation, the most striking feature was an inhibition of the mandibular basal convexity, the absence of teeth and alveolar bone processes, and absence of endochondral ossification in the mandibular condyle. At birth, in Msx1+/- heterozygous animals, we identified for the first time a double Msx1 aboral-oral and disto-proximal gradient field developmental pattern located in the low border of the mandibular bone in relation with this bone segment modeling. Msx1 expression involved both osteoblast and osteoclast cells. A distinct pattern characterized bone surfaces: Periosteum osteoblast differentiation was related to Msx1 down-regulation, while in the endosteum both differentiated osteoblasts and osteoclasts expressed the homeoprotein. In postnatal stages, Msx1 expression was maintained in the alveolar bone processes and dento-alveolar cells in relation with tooth function. Our data suggest that Msx1 play a role in a site-specific manner not only in early patterning but also in skeletal growth and modeling by acting on heterogenous bone cell populations.

Cross-talk between Msx/Dlx homeobox genes and vitamin D during tooth mineralization.

Rickets is associated with site-specific disorders of enamel and dentin formation, which may reflect the impact of vitamin D on a morphogenetic pathway. This study is devoted to potential cross-talk between vitamin D and Msx/Dlx transcription factors. We raised the question of a potential link between tooth defects seen in mice with rickets and Msx2 gene misexpression, using mutant mice lacking the nuclear vitamin D receptor as an animal model. Our data showed a modulation of Msx2 expression. In order to search for a functional impact of this Msx2 misexpression secondary to rickets, we focused our attention on osteocalcin as a target gene for both vitamin D and Msx2. Combining Msx2 overexpression and vitamin D addition in vitro, we showed an inhibitory effect on osteocalcin expression in immortalized MO6-G3 odontoblasts. Finally, in the same cells, such combinations appeared to modulate VDR expression outlining the existence of complex cross-regulations between vitamin D and Msx/Dix pathways.

Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth.

Biochemical investigations in rodents have shown that numerous mineralized matrix proteins share expression in bone, dentin, and cementum. Little information is available regarding the expression pattern of these proteins in human tissues, particularly during tooth formation. The aim of this study was to identify the expression pattern of the two major noncollagenous proteins of bone and dentin, osteocalcin (OC) and osteonectin (ON), in comparison to the dentin-specific protein, dentin sialophosphoprotein (DSPP). Mandibles from fetuses (5-26 weeks), neonate autopsies, forming teeth from 10-12-year-old patients, third molars extracted for orthodontic reasons, and bone tumors were collected with approval from the National Ethics Committee. Human OC, ON, and DSPP mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR) in fetal mandibles (5-11 weeks) and in primary cell cultures of dental pulp. In addition, OC, ON, and DSPP proteins were localized in forming human mineralized tissues using immunohistochemistry. In vivo, DSPP expression was associated with tooth terminal epithelial-mesenchymal interaction events, amelogenesis and dentinogenesis. Transient DSPP expression was seen in the presecretory ameloblasts with continuous expression in the odontoblasts. In contrast, both osteoblasts and odontoblasts showed a temporal gap between OC and ON expression in early development. ON was expressed in the initial stages of cytodifferentiation, whereas OC was expressed only during the later stages, especially in the teeth. At the maturation stage of enamel formation, both proteins were detected in odontoblasts and their processes within the extracellular matrix. In contrast to bone, OC was not localized extracellularly within the collagen-rich dentin matrix (predentin or intertubular dentin), but was found in the mature enamel. ON was present mostly in the nonmineralized predentin. These results demonstrate for the first time that both OC and ON are produced by human odontoblasts and determine the expression pattern of DSPP in human teeth, and suggest that OC and ON move inside the canalicule via odontoblast cell processes becoming localized to specific extracellular compartments during dentin and enamel formation. These distinct extracellular patterns may be related to the nature of DSPP, OC, and ON interactions with other matrix-specific macromolecules (i.e., amelogenin, dentin matrix protein-1) and/or to the polarized organization of odontoblast secretion as compared with osteoblasts.