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Psychopathological differences among three groups of school children affected by the war in Croatia.

The consequences of extreme violence such as war torture affect children in different ways and may immediately manifest at the physical and/or psychologic level, or may remain hidden and unrecognized for years. The victims are usually very reluctant to speak about their traumatic experiences, and try to deny the existence of psychological disturbances. They often seek help for somatic problems. Taking these physical complaints seriously helps to progressively reach the psychological effects of violence. Therefore, identification of such children should be directed to more complete evaluation of their symptomatology and functioning. This can be done by: a) individual evaluation to get enough information on the historical events, functioning and symptoms of these children; and b) standardized instruments which may allow the children to disclose more about their psychological experiences during the war. In this study rating scales and assessment instruments for children aged < 15, such as CPRS with General Scoring Sheet (Fish, 1985), were used to assess the broad spectrum of psychopathology in this age group. These questionnaires were used in a large group of school children (N = 1888), 989 girls and 899 boys aged 7-16 years. The sample was divided into 3 groups: 843 non-displaced, 377 displaced and 669 refugee children. Results of statistical analysis (arithmetical mean and standard deviation of discriminative variables transformed in Z-values with F-ratio) showed the three groups of children (non-displaced, displaced and refugees) to significantly differ in 13 out of 15 psychopathologic clusters. Discriminative cannonic analysis of the 3 groups of children (non displaced, displaced and refugees) also showed significant differences. The first discriminative function (80.24% of total variance) indicated depression, violence and antisocial behavior to be rare in non-displaced children, more pronounced in displaced, and most pronounced in refugee children. The second discriminative function (19.76% of total variance) showed hyperactivity, anxiety and psychosomatic disturbances to be rare in non-displaced children; more frequent in refugee, and most expressed in displaced children. According to the results, the authors concluded that war is very painful for a large group of children, among whom the displaced and refugee children are most affected by psychopathologic disturbances.

Adolescent↗

Visible vs hidden scars and their relation to body esteem.

This study examined the relationship among burn scarring, severity and visibility, and body esteem. Previous work addressing this question has relied on case studies and small samples. We mailed a survey to 2500 members of a national burn survivor support group. Survivors were asked to complete and return the mailed survey or complete the survey on line at our Web site. Three hundred sixty-one survivors completed all questionnaires in the survey relevant to this study, which included measures of burn characteristics, social stigmatization, social support, depression, and body esteem. The sample characteristics were as follows: 52% were women, the mean age was 44.1 years, the mean age burned was 26 years, 88% were European American, 5% were African American, 4% were multiracial, 3% were other, the average TBSA was 48%, and the mean educational level was high school graduate. We measured scar visibility by asking survivors to rate "how often are your burn scars visible to others" on a six-point scale. We also asked them to rate the presence or absence of scars on 15 body parts, total TBSA, and number of surgeries. The correlation between visible scarring and different aspects of body esteem, that is, self-satisfaction with appearance (-.19) and perception of others reaction to your appearance (-.27), was statistically significant but low. Visible scarring was unrelated to self-satisfaction with weight (.01). Visible scarring had a low but significant correlation with perceived stigmatization (.23) and was not correlated with depression (0.01). Other measures of scarring also had low correlations with social and emotional outcome variables. Because scar severity and visibility are hypothesized to be particularly relevant to body esteem, we performed a multiple regression predicting body esteem. We entered the variables in three blocks: burn characteristics, demographic characteristics, and social and emotional characteristics. Burn characteristics accounted for less than 20% of the variance. R square for the final equation equaled.62, with social adjustment and depression accounting for the largest portion of the variance. In this sample, burn scar visibility and severity did not have a strong relationship with social and emotional adjustment variables. More effort must be placed into developing psychosocial interventions that help survivors accept scars, reduce depression, and build a strong loving support system.

Adult↗

Postoperative pain management in orthopaedic patients: no differences in pain score, but improved stress control by epidural anaesthesia.

BACKGROUND AND OBJECTIVE: To investigate the interactions of postoperative pain and endocrine stress response, three groups of 21 patients each with total knee arthroplasty were compared in a randomized, prospective design. For postoperative pain management, a three-in-one block, an epidural catheter analgesia or an intravenous patient-controlled analgesia was used. METHODS: After standardized balanced anaesthesia, the pain intensity was measured by a visual analogue scale (VAS). For detection of epinephrine, norepinephrine, antidiuretic hormone, adrenocorticotropic hormone and cortisol in the plasma, blood samples were taken at six time points before and up to 180 min after the start of pain therapy. In addition, systolic arterial pressure, heart rate, partial arterial oxygen saturation, nausea, vomiting and satisfaction of the patients were recorded. RESULTS: Within 15 min after the start of pain therapy, VAS in all groups was similarly reduced from >40 mm to a range <10 mm (P < 0.001). Initially, all endocrine stress variables exceeded the normal range. Epidural anaesthesia led to a significant decrease of epinephrine and norepinephrine concentrations, while an increase was observed in the group with patient-controlled analgesia, and the decrease in patients with the three-in-one block was less than in patients receiving epidural anaesthesia (P = 0.001). Differences in antidiuretic hormone, adrenocorticotropic hormone and cortisol were less pronounced. Systolic arterial pressure decreased significantly in all groups, particularly in patients with epidural anaesthesia. Partial arterial oxygen saturation and the incidence of nausea and vomiting were comparable. All patients were satisfied with the methods used. CONCLUSIONS: All methods of pain management led to sufficient analgesia, but they were not accompanied by an adequate reduction in endocrine stress response. Thus, postoperative pain is only a secondary stressor and sufficient analgesia with subjective well-being does not prove a stress-free state. With regard to the reduction of sympathoadrenergic stress response, epidural anaesthesia is superior to the three-in-one block and patient-controlled analgesia. Epidural anaesthesia is recommended particularly for high-risk patients with hypertension, coronary heart disease and diabetes mellitus. In these patients, the reduction of a 'hidden' endocrine stress response in addition to prevention of pain is of special interest.

Aged↗

Prediction of bladder outlet obstruction in men with lower urinary tract symptoms using artificial neural networks.

PURPOSE: To evaluate the performance of a backpropagation artificial neural network (ANN) in the diagnosis of men with lower urinary tract symptoms (LUTS) and to compare its performance to that of a traditional linear regression model. MATERIALS AND METHODS: 1903 LUTS patients referred to the University Hospital Nijmegen between 1992 and 1998 received routine investigation, consisting of transrectal ultrasonography of the prostate, serum PSA measurement, assessment of symptoms and quality of life by the International Prostate Symptom Score (IPSS), urinary flowmetry with determination of maximum flow rate (Qmax), voided volume and post-void residual urine and full pressure flow studies (PFS). Using a three-layered backpropagation ANN with three hidden nodes, the outcome of PFS, quantified by the Abrams-Griffiths number (AG-number), was estimated based on all available non-invasive diagnostic test results plus patient age. The performance of the network was quantified using sensitivity, specificity and the area under the ROC-curve (AUC). The results of the neural network approach were compared to those of a linear regression analysis. RESULTS: Prostate volume, Qmax, voided volume and post void residual urine showed substantial predictive value concerning the outcome of PFS. Patient age, PSA-level, IPSS and Quality of life did not add to that prediction. Using a cut-off value in predicted and true AG-numbers of 40 cm. H2O, the neural network approach yielded sensitivity and specificity of 71% and 69%, respectively. The AUC of the network was 0.75 (standard error = 0.01). A linear regression model produced identical results. CONCLUSIONS: This study shows that at an individual level, the outcome of PFS cannot be predicted accurately by the available non-invasive tests. The use of ANNs, which are better able than traditional regression models to identify non-linear relations and complex interactions between variables, did not improve the prediction of BOO. Thus, if precise urodynamic information is considered important in the diagnosis of men with LUTS, PFS must be carried out. Both neural networks and regression analysis appear promising to identify patients who should undergo PFS, and those in whom PFS can safely be omitted. Furthermore, the ability of ANNs and regression models to predict treatment result should be evaluated.

Humans↗

Hidden diversity in Enterococcus faecalis revealed by CRISPR2 screening: eco-evolutionary insights into a novel subspecies.

Enterococcus faecalis is a commensal bacterium that colonizes the gut of humans and animals and is a major opportunistic pathogen, known for causing multidrug-resistant healthcare-associated infections (HAIs). Its ability to thrive in diverse environments and disseminate antimicrobial resistance genes (ARGs) across ecological niches highlights the importance of understanding its ecological, evolutionary, and epidemiological dynamics. The CRISPR2 locus has been used as a valuable marker for assessing clonality and phylogenetic relationships in E. faecalis. In this study, we identified a group of E. faecalis strains lacking CRISPR2, forming a distinct, well-supported clade. We demonstrate that this clade meets the genomic criteria for classification as a novel subspecies, here referred to as "subspecies B." Through a comprehensive pangenome analysis and comparative genomics, we explored the adaptive ecological traits underlying this diversification process, identifying clade-specific features and their predicted functional roles. Our findings suggest that the frequent isolation of subspecies B from meat products and processing facilities may reflect dissemination routes involving environmental contamination (e.g., water, plants, soil) from avian species. The absence of key virulence traits required for pathogenicity in mammals, particularly humans, and the lack of clinically relevant resistance determinants indicate that subspecies B currently poses minimal threat to public health compared with the broadly disseminated "subspecies A." Nevertheless, the unclear potential for genetic exchange between these subspecies and the frequent association of subspecies B with food sources calls for continued genomic surveillance of E. faecalis from a One Health perspective to detect and mitigate the emergence of high-risk variants in advance.IMPORTANCEExploring intraspecific genetic variability in generalist bacteria with pathogenic potential, such as Enterococcus faecalis, is a key to uncovering stable evolutionary trends. By screening the CRISPR2 locus across a representative set of genomes from diverse sources, this study reveals a previously unrecognized lineage within the population structure of E. faecalis, associated with underexplored nonhuman and nonhospital reservoirs. These findings broaden our knowledge of the species' genetic landscape and shed light on its adaptive strategies and patterns of ecological dissemination. By bridging phylogenetic patterns with variation in genetic defense systems and accessory traits, the study generates testable hypotheses about the genomic determinants and corresponding selective pressures that shape the species' behavior and long-term dissemination. This work offers new perspectives on the eco-evolutionary dynamics of E. faecalis and highlights the value of genomic surveillance beyond clinical settings, in alignment with One Health principles.

Enterococcus faecalis↗

Interpretation of steady-state current-voltage curves: consequences and implications of current subtraction in transport studies.

A problem often confronted in analyses of charge-carrying transport processes in vivo lies in identifying porter-specific component currents and their dependence on membrane potential. Frequently, current-voltage (I-V)--or more precisely, difference-current-voltage (dI-V)--relations, both for primary and for secondary transport processes, have been extracted from the overall membrane current-voltage profiles by subtracting currents measured before and after experimental manipulations expected to alter the porter characteristics only. This paper examines the consequences of current subtraction within the context of a generalized kinetic carrier model for Class I transport mechanisms (U.-P. Hansen, D. Gradmann, D. Sanders and C.L. Slayman, 1981, J. Membrane Biol. 63:165-190). Attention is focused primarily on dI-V profiles associated with ion-driven secondary transport for which external solute concentrations usually serve as the experimental variable, but precisely analogous results and the same conclusions are indicated in relation to studies of primary electrogenesis. The model comprises a single transport loop linking n (3 or more) discrete states of a carrier 'molecule.' State transitions include one membrane charge-transport step and one solute-binding step. Fundamental properties of dI-V relations are derived analytically for all n-state formulations by analogy to common experimental designs. Additional features are revealed through analysis of a "reduced" 2-state empirical form, and numerical examples, computed using this and a "minimum" 4-state formulation, illustrate dI-V curves under principle limiting conditions. Class I models generate a wide range of dI-V profiles which can accommodate essentially all of the data now extant for primary and secondary transport systems, including difference current relations showing regions of negative slope conductance. The particular features exhibited by the curves depend on the relative magnitudes and orderings of reaction rate constants within the transport loop. Two distinct classes of dI-V curves result which reflect the relative rates of membrane charge transit and carrier recycling steps. Also evident in difference current relations are contributions from 'hidden' carrier states not directly associated with charge translocation in circumstances which can give rise to observations of counterflow or exchange diffusion. Conductance-voltage relations provide a semi-quantitative means to obtaining pairs of empirical rate parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

CGHPRO -- a comprehensive data analysis tool for array CGH.

BACKGROUND: Array CGH (Comparative Genomic Hybridisation) is a molecular cytogenetic technique for the genome wide detection of chromosomal imbalances. It is based on the co-hybridisation of differentially labelled test and reference DNA onto arrays of genomic BAC clones, cDNAs or oligonucleotides, and after correction for various intervening variables, loss or gain in the test DNA can be indicated from spots showing aberrant signal intensity ratios. Now that this technique is no longer confined to highly specialized laboratories and is entering the realm of clinical application, there is a need for a user-friendly software package that facilitates estimates of DNA dosage from raw signal intensities obtained by array CGH experiments, and which does not depend on a sophisticated computational environment. RESULTS: We have developed a user-friendly and versatile tool for the normalization, visualization, breakpoint detection and comparative analysis of array-CGH data. CGHPRO is a stand-alone JAVA application that guides the user through the whole process of data analysis. The import option for image analysis data covers several data formats, but users can also customize their own data formats. Several graphical representation tools assist in the selection of the appropriate normalization method. Intensity ratios of each clone can be plotted in a size-dependent manner along the chromosome ideograms. The interactive graphical interface offers the chance to explore the characteristics of each clone, such as the involvement of the clones sequence in segmental duplications. Circular Binary Segmentation and unsupervised Hidden Markov Model algorithms facilitate objective detection of chromosomal breakpoints. The storage of all essential data in a back-end database allows the simultaneously comparative analysis of different cases. The various display options facilitate also the definition of shortest regions of overlap and simplify the identification of odd clones. CONCLUSION: CGHPRO is a comprehensive and easy-to-use data analysis tool for array CGH. Since all of its features are available offline, CGHPRO may be especially suitable in situations where protection of sensitive patient data is an issue. It is distributed under GNU GPL licence and runs on Linux and Windows.

Algorithms↗

[Use of the calvarium for bone grafting in cranio-maxillo-facial surgery].

Bone grafts's traditional donor sites in cranio-maxillo-facial surgery have been for many years and are still in some occasions the ribs, iliac crest and tibia. Bone grafts taken from the calvaria have been used by some surgeons in the past but its wide acceptance was only achieved after Paul Tessier had reported his own experience. The calvaria is composed of inner and outer tables that encloses a layer of cancellous bone called the diploe. A high degree of variability exist with respect to skull thickness. Nevertheless parietal bones is the preferable site for the harvesting of the graft. The embryonic origin of the cranium should be responsible for greater survival of the graft. Membranous bone would maintain its volume to a greater extent than endochondral bone when autografted in the cranio-facial region. However this remains controversial. Two techniques can be used for the harvesting of a calvarial bone grafts. A split thickness calvarial graft involves removal of the outer table while leaving the inner layer in place. Its main disadvantage is the relatively thinness of the bone transferred. A full thickness segment of skull involves the cranium cavity be entered. A half of the graft can be split along the diploe space and returned to fill the donor site. The other half is used for reconstruction. It is a more complicated procedure. Cranial grafts have been used in the following cases. Correction of contour defect of the forehead and zygomatic bones, orbital floor reconstruction, restoration of the nasal bridge, bone grafting of the maxilla and mandibule. The advantages are the following: the donor and recipient sites are in adjacent surgical fields, the donor site scar is hidden in the scalp, morbidity associated with removing the graft is almost inexistent. (ABSTRACT TRUNCATED AT 250 WORDS)

Craniosynostoses↗

Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis.

UNLABELLED: A genome-wide screen was conducted using a large white sample to identify QTLs for FNCS geometry. We found significant linkage of FNCS parameters to 20q12 and Xq25, plus significant epistatic interactions and sex-specific QTLs influencing FNCS geometry variation. INTRODUCTION: Bone geometry, a highly heritable trait, is a critical component of bone strength that significantly determines osteoporotic fracture risk. Specifically, femoral neck cross-sectional (FNCS) geometry is significantly associated with hip fracture risk as well as genetic factors. However, genetic research in this respect is still in its infancy. MATERIALS AND METHODS: To identify the underlying genomic regions influencing FNCS variables, we performed a remarkably large-scale whole genome linkage scan involving 3998 individuals from 434 pedigrees for four FNCS geometry parameters, namely buckling ratio (BR), cross-sectional area (CSA), cortical thickness (CT), and section modulus (Z). The major statistical approach adopted is the variance component method implemented in SOLAR. RESULTS: Significant linkage evidence (threshold LOD = 3.72 after correction for tests of multiple phenotypes) was found in the regions of 20q12 and Xq25 for CT (LOD = 4.28 and 3.90, respectively). We also identified eight suggestive linkage signals (threshold LOD = 2.31 after correction for multiple tests) for the respective geometry traits. The above findings were supported by principal component linkage analysis. Of them, 20q12 was of particular interest because it was linked to multiple FNCS geometry traits and significantly interacted with five other genomic loci to influence CSA variation. The effects of 20q12 on FNCS geometry were present in both male and female subgroups. Subgroup analysis also revealed the presence of sex-specific quantitative trait loci (QTLs) for FNCS traits in the regions such as 2p14, 3q26, 7q21 and 15q21. CONCLUSIONS: Our findings laid a foundation for further replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning FNCS geometry variation and the associated hip fractures.

Adult↗

Immunoglobulin VH determinants defined by monoclonal antibodies.

Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts.

Animals↗

Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones.

We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.

Adult↗

Reproductive outcomes among Mexico-born women in San Diego and Tijuana: testing the migration selectivity hypothesis.

Mexican immigrants to the United States have better reproductive outcomes than do U.S.-born non-Latina whites. Explanations offered for this "epidemiologic paradox" include (1) poor outcomes among Mexican women may be hidden by their return to Mexico; (2) Mexican women may have a higher fetal death rate that alters the pattern of live birth outcomes; (3) Mexican women may have socioeconomic characteristics which, if properly measured, would explain the outcome; (4) Mexican women may have personal characteristics which would explain the outcome, if properly measured; (5) there may be ameliorative or salutogenic "protective" effects of culture; and (6) migration may be selective of healthier women who are thus more prone to positive outcomes. We test these explanations, with an emphasis on the last one, using a data set that combines reproductive histories and birth outcomes for Mexico-born women delivering in San Diego, California and Mexican women delivering in Tijuana, Mexico. These data are compared with U.S.-born Latinas and U.S.-born non-Latina Whites. Multivariate logistic regression analysis suggests that when controlling for birth history (stillbirths and miscarriages), socioeconomic characteristics (education and prenatal visits), personal characteristics (age, parity, time in area, history of family problems), and health characteristics (history of smoking, alcohol use, drug use, anemia, vaginal bleeding, urinary infection), the adjusted odds of a positive birth outcome (measured as a live birth of 2500 grams or more) is highest for women delivering in Tijuana, implying that migrants may not be so selective when compared to the country of origin. The number of prenatal visits was an important explanatory variable.

Journal Article↗

Modelling viral impact on bacterioplankton in the North Sea using artificial neural networks.

The temporal variability of the viral impact on bacterioplankton during the summer-winter transition in the North Sea was determined and artificial neural networks (ANNs) were developed to predict viral production and the frequency of infected bacterial cells (FIC). Viral production and FIC were estimated using a virus-dilution approach during four cruises in the southern North Sea between July and December 2000 and an additional cruise in June 2001. Supplementary data such as bacterial production, and bacterial and viral abundance were collected to relate changes in FIC and viral production to the dynamics of other biotic parameters. Average viral abundance varied between 4.4 x 10(6) ml(-1) in December and 29.8 x 10(6) ml(-1) in July. Over the seasonal cycle, viral abundance correlated best with bacterial production. Average bacterial abundance varied between 0.5 x 10(6) ml(-1) in December and 1.3 x 10(6) ml(-1) in July. Monthly average values of FIC ranged from 9% in September to 39% in June and the average viral production from 11 x 10(4) ml(-1) h(-1) in December to 35 x 10(4) ml(-1) h(-1) in July. The data set was used to develop ANN-based models of viral production and FIC. Viral production was modelled best using sampling time, and bacterial and viral abundance as input parameters to an ANN with two hidden neurons. Modelling of FIC was performed using bacterial production as an additional input parameter for an ANN with three hidden neurons. The models can be used to simulate viral production and FIC based on regularly recorded and easily obtainable parameters such as bacterial production, bacterial and viral abundance.

Bacteria↗

Neuroretinitis.

Despite the growing list of agents that can present as neuroretinitis, nearly one-half remain idiopathic. However, many of the candidate etiologies are treatable conditions, and accurate diagnosis can result in visual rehabilitation. A complete workup in patients presenting with acute neuroretinitis should include a thorough history and general medical evaluation. Exposure history should be thoroughly explored, including recent travel, unpasteurized and uncooked foods, sexual experience, and animal contacts. A detailed physical examination should be performed to note hidden rashes and inoculation sites and should include routine measurements of blood pressure and heart rate. Laboratory tests should be tailored to the history and may include complete blood count; erythrocyte sedimentation rate; bacterial, fungal, and viral blood cultures; antinuclear antibody test; angiotensin-converting enzyme; anti-double-stranded DNA; and C3. Serological evaluation should look for syphilis, Lyme disease, histoplasmosis, brucellosis, chlamydia, HIV, toxoplasmosis, Epstein-Barr virus, viral hepatitis B and C, and tuberculin skin test. Neuroretinitis is a clinical entity in which there is inflammation of the retinal architecture and optic nerve. There are numerous entities that can cause a picture of neuroretinitis ranging from vascular to infectious to autoimmune. With regards to the infectious etiologies, it is interesting to note that many of these organisms are obligate intracellular pathogens. The microorganisms B. henselae, T. gondii, R. typhi, T. pallidum, Mycobacterium tuberculosis, Histoplasma capsulatum, and various viruses, such as HIV, mumps, and HSV, are known intracellular agents. Other major infectious agents, such as B. burgdorferi and Leptospirosis spp. are known to remain sequestered within the circulatory system. It is possible that in this way these agents are able to breach the delicate blood-brain barrier. The implication of such findings on the treatment and management of neuroretinitis remains to be explored. Interestingly, the vast majority of infected patients do not develop neuroretinitis or demonstrate CNS involvement. Detailed examination of this variability may provide further insight into the pathogenic properties of these infectious agents, host tissue susceptibility, and mechanisms of blood-retina barrier integrity. A detailed retinal examination can provide an unobstructed view of the CNS. Careful inspection of this delicate interface may reveal subtle findings critical for accurate and rapid diagnosis of underlying systemic pathology. The varied visual and neurological symptoms of neuroretinitis attest to the fact that this is a disease of both the retina and contiguous neuronal elements. Such involvement significantly elevates the risk to the patient and emphasizes the need for early detection and prompt treatment.

Humans↗

Risk analyses for the cognitive phenotype in Turner's syndrome: evidence of familial influence as a decisive factor.

The interindividual varying cognitive performance in female patients with Turner's syndrome has usually been attributed to the interindividual varying mosaicism with a consecutive variable loss of X-chromosome DNA or to secondary risk factors such as estrogen deficiency owing to ovarian failure. The aim of our study was to determine the specific impact of X chromosome-related features and associated risk factors, on the one hand and familial influences, on the other hand on the interindividual variation in the cognitive phenotype. One hundred and one subjects with Turner's syndrome and 53 sisters as controls for familial influences were examined by comparing the cognitive information processing abilities (Kaufmann Assessment Battery for Children [K-ABC]). Subjects with Turner's syndrome performed at a significantly lower level than sisters on all subscales (eg, Mental Processing Composite: Turner's syndrome 86.4 [SD 15.0] versus sisters 99.3 [SD 10.6]; P < .001). For the neurocognitive phenotype in subjects with Turner's syndrome, a significant correlation was found only with the sisters' cognitive abilities (Mental Processing Composite: r = .38, P < .05). In contrast, neither the individual mosaic status nor the known associated risk factors predicted the neurocognitive phenotype in Turner's syndrome. These results are corroborated in the regression analyses in those subjects with Turner's syndrome with a sister (Simultaneous Processing(sister) for Simultaneous Processing(Turner's syndrome): beta = .346, P < .05, corrected R2 = .049; and Mental Processing Composite(sister) for Mental Processing Composite(Turner's syndrome): beta = .354, P < .05, corrected R2 = .033). The interindividual variation of intellectual abilities in Turner's syndrome seems to be primarily related to familial coinfluences and not to the interindividual varying loss of X-chromosome DNA in terms of hidden mosaicism or potential associated risk factors.

Child↗

The application of methods of non-linear dynamics for the improved and predictive recognition of patients threatened by sudden cardiac death.

OBJECTIVES: This study introduces new methods of non-linear dynamics (NLD) and compares these with traditional methods of heart rate variability (HRV) and high resolution ECG (HRECG) analysis in order to improve the reliability of high risk stratification. METHODS: Simultaneous 30 min high resolution ECG's and long-term ECG's were recorded from 26 cardiac patients after myocardial infarction (MI). They were divided into two groups depending upon the electrical risk, a low risk group (group 2, n = 10) and a high risk group (group 3, n = 16). The control group consisted of 35 healthy persons (group 1). From these electrocardiograms we extracted standard measures in time and frequency domain as well as measures from the new non-linear methods of symbolic dynamics and renormalized entropy. RESULTS: Applying discriminant function techniques on HRV analysis the parameters of non-linear dynamics led to an acceptable differentiation between healthy persons and high risk patients of 96%. The time domain and frequency domain parameters were successful in less than 90%. The combination of parameters from all domains and a stepwise discriminant function separated these groups completely (100%). Use of this discriminant function classified three patients with apparently low (no) risk into the same cluster as high risk patients. The combination of the HRECG and HRV analysis showed the same individual clustering but increased the positive value of separation. CONCLUSIONS: The methods of NLD describe complex rhythm fluctuations and separate structures of non-linear behavior in the heart rate time series more successfully than classical methods of time and frequency domains. This leads to an improved discrimination between a normal (healthy persons) and an abnormal (high risk patients) type of heart beat generation. Some patients with an unknown risk exhibit similar patterns to high risk patients and this suggests a hidden high risk. The methods of symbolic dynamics and renormalized entropy were particularly useful measures for classifying the dynamics of HRV.

Death, Sudden, Cardiac↗

Hidden Markov event sequence models: toward unsupervised functional MRI brain mapping.

RATIONALE AND OBJECTIVES: Most methods used in functional MRI (fMRI) brain mapping require restrictive assumptions about the shape and timing of the fMRI signal in activated voxels. Consequently, fMRI data may be partially and misleadingly characterized, leading to suboptimal or invalid inference. To limit these assumptions and to capture the broad range of possible activation patterns, a novel statistical fMRI brain mapping method is proposed. It relies on hidden semi-Markov event sequence models (HSMESMs), a special class of hidden Markov models (HMMs) dedicated to the modeling and analysis of event-based random processes. MATERIALS AND METHODS: Activation detection is formulated in terms of time coupling between (1) the observed sequence of hemodynamic response onset (HRO) events detected in the voxel's fMRI signal and (2) the "hidden" sequence of task-induced neural activation onset (NAO) events underlying the HROs. Both event sequences are modeled within a single HSMESM. The resulting brain activation model is trained to automatically detect neural activity embedded in the input fMRI data set under analysis. The data sets considered in this article are threefold: synthetic epoch-related, real epoch-related (auditory lexical processing task), and real event-related (oddball detection task) fMRI data sets. RESULTS: Synthetic data: Activation detection results demonstrate the superiority of the HSMESM mapping method with respect to a standard implementation of the statistical parametric mapping (SPM) approach. They are also very close, sometimes equivalent, to those obtained with an "ideal" implementation of SPM in which the activation patterns synthesized are reused for analysis. The HSMESM method appears clearly insensitive to timing variations of the hemodynamic response and exhibits low sensitivity to fluctuations of its shape (unsustained activation during task). Real epoch-related data: HSMESM activation detection results compete with those obtained with SPM, without requiring any prior definition of the expected activation patterns thanks to the unsupervised character of the HSMESM mapping approach. Along with activation maps, the method offers a wide range of additional fMRI analysis functionalities, including activation lag mapping, activation mode visualization, and hemodynamic response function analysis. Real event-related data: Activation detection results confirm and validate the overall strategy that consists in focusing the analysis on the transients, time-localized events that are the HROs. CONCLUSION: All the experiments performed on synthetic and real fMRI data demonstrate the relevance of HSMESMs in fMRI brain mapping. In particular, the statistical character of these models, along with their learning and generalizing abilities are of particular interest when dealing with strong variabilities of the active fMRI signal across time, space, experiments, and subjects.

Adolescent↗

[Occipital spectral EEG parameters in newly diagnosed, untreated patients with epilepsy].

INTRODUCTION: Minor spectral EEG alterations hidden to the naked eye may be of interest in the field of epileptology, cognitive performances, and drug effects. In order to introduce new scientific results of brain wave research into the clinical field of epilepsy- and drug-related cognitive problems, a normative quantitative EEG database for epilepsy was constructed. PATIENTS AND METHODS: 171 newly referred, five to 50 years old patients with untreated "new" epilepsy (that is, clinical, EEG, MRI investigations had been done in 24 months after the first unprovoked seizure) were collected. EEG was recorded with closed eyes, in the waking-relaxed state. Effects that are known to influence EEG spectra (nearby seizures, drugs, etc.) were excluded as far as possible. A total of two minutes of waking-resting EEG activity was chosen for spectral analysis. Fast Fourier transformation of the selected samples were calculated resulting in absolute power, percent power and mean alpha frequency (AA, RA, and AMF respectively) for the right and left occipital derivations. For each patient (and also for 37 healthy controls), the deviation of the individual values from the age-adjusted normative mean was expressed in Z-score. Main diagnostic epilepsy categories were compared to the control group as well as to each other. In addition, effects of MRI-defined cerebral lesions and interictal spiking on spectral EEG parameters were investigated. RESULTS: All group averages were within the 95 per cent confidence interval. Overwhelming majority of the individual data fell within a 3Z range. Statistically significant differences were found for AA and RA, but seldom for AMF. Right and left alpha-parameters were surprisingly symmetrical in all groups. The main difference between epilepsy groups and controls was less AA and RA power in the epilepsy groups. MRI-defined lesions and interictal epileptiform activity did not significantly influence EEG spectral variables. CONCLUSION: These results might serve as reference data and might help planning of further quantitative EEG studies in the triangle of epilepsy, cognitive problems, and drug effects.

Adolescent↗