Activities of daily living with reverse prostheses: importance of scapular compensation for functional mobility of the shoulder.

HYPOTHESIS: The nonanatomical design of reverse shoulder prostheses induce medial displacement of the center of rotation, impingements and may reduce the mobility of the shoulder. The aim of this study is to test the hypothesis that during activities of daily living functional mobility of the shoulder can be restored by scapular compensation. MATERIAL AND METHODS: A numerical 3-dimensional model was developed to reproduce the movement of the scapula and humerus, during 4 activities of daily living measured experimentally. This hypothesis was tested in 4 configurations of the aequalis reverse prosthesis (standard 36-mm glenosphere, 42-mm glenosphere, lateralized 36-mm glenosphere, lateralized Bony Increased-Offset Reverse Shoulder Arthroplasty [BIO-RSA]), which were implanted in the virtual model. All impingement positions were evaluated, as the required scapular compensation to avoid impingements. RESULTS: With the 36-mm glenosphere, impingements occurred only for rest of hand to back-pocket positions. The 42-mm partly improved the mobility. The 2 lateralized glenospheres were free of impingement. When impingements occurred, the scapular compensation was less than 10°. CONCLUSION: Most reverse prostheses impingements reported in clinical and biomechanical studies can be avoided, either by scapular compensation or by a glenosphere lateralization. After reverse shoulder arthroplasty, a fraction of the mobility of the gleno-humeral is transferred to the scapulo-thoracic joint.

Functional analysis of disease-causing NR2E3 mutations

Purpose:We analyzed the transcriptional activity of disease-causing NR2E3 mutant proteins in a heterologous system. NR2E3 belongs to the nuclear receptor superfamily of transcription factors, characterized by evolutionary-conserved DNA-binding (DBD) and ligand-binding (LBD) domains. NR2E3 acts in concert with the transcription factors CRX and NRL to repress cone-specific genes and activate rod-specific genes in rod photoreceptors. During development, NR2E3 is also required to suppress cone cell generation from retinal progenitor cells. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S-) cone syndrome (ESCS), the Goldman-Favre syndrome, and, more recently, with autosomal dominant retinitis pigmentosa (adRP). Methods:The different NR2E3 mutants were generated by QuickChangeR mutagenesis and analyzed by transfection in heterologous HEK293T cells. Results:In transactivation assays in HEK293T cells, the adRP-linked p.G56R mutant protein exhibited a more severe effect both in activation of a rhodopsin promoter reporter construct and in repression of M-opsin promoter reporter construct, than the ESCS-linked R76Q, R76W, G88V, R97H, R104Q, R104W mutants of the DBD. In contrast, the ESCS-linked p.R311Q mutant of the LBD behaved like the NR2E3 wild-type protein in these assays. By co-expressing the corepressors atrophin-1 and -2, a differential repression of the M-opsin promoter was observed in presence of the p.R311Q, p.R385P and p.M407K. Interestingly, corepressor expression also affected the activity of CRX, but not NRL, in both rhodopsin and M-opsin transactivation assays. Conclusions:Taken together, these in vitro results suggest a distinct disease mechanism for the adRP-linked mutation, but open the possibility of different mechanisms for the development of ESCS that is clinically characterized by important phenotypic variations.

Constructing brain functional networks from EEG: partial and unpartial correlations.

We consider electroencephalograms (EEGs) of healthy individuals and compare the properties of the brain functional networks found through two methods: unpartialized and partialized cross-correlations. The networks obtained by partial correlations are fundamentally different from those constructed through unpartial correlations in terms of graph metrics. In particular, they have completely different connection efficiency, clustering coefficient, assortativity, degree variability, and synchronization properties. Unpartial correlations are simple to compute and they can be easily applied to large-scale systems, yet they cannot prevent the prediction of non-direct edges. In contrast, partial correlations, which are often expensive to compute, reduce predicting such edges. We suggest combining these alternative methods in order to have complementary information on brain functional networks.

Functional analysis: evaluation of response intensities--tailoring ANOVA for lists of expression subsets.

Background: Microarray data is frequently used to characterize the expression profile of a whole genome and to compare the characteristics of that genome under several conditions. Geneset analysis methods have been described previously to analyze the expression values of several genes related by known biological criteria (metabolic pathway, pathology signature, co-regulation by a common factor, etc.) at the same time and the cost of these methods allows for the use of more values to help discover the underlying biological mechanisms. Results: As several methods assume different null hypotheses, we propose to reformulate the main question that biologists seek to answer. To determine which genesets are associated with expression values that differ between two experiments, we focused on three ad hoc criteria: expression levels, the direction of individual gene expression changes (up or down regulation), and correlations between genes. We introduce the FAERI methodology, tailored from a two-way ANOVA to examine these criteria. The significance of the results was evaluated according to the self-contained null hypothesis, using label sampling or by inferring the null distribution from normally distributed random data. Evaluations performed on simulated data revealed that FAERI outperforms currently available methods for each type of set tested. We then applied the FAERI method to analyze three real-world datasets on hypoxia response. FAERI was able to detect more genesets than other methodologies, and the genesets selected were coherent with current knowledge of cellular response to hypoxia. Moreover, the genesets selected by FAERI were confirmed when the analysis was repeated on two additional related datasets. Conclusions: The expression values of genesets are associated with several biological effects. The underlying mathematical structure of the genesets allows for analysis of data from several genes at the same time. Focusing on expression levels, the direction of the expression changes, and correlations, we showed that two-step data reduction allowed us to significantly improve the performance of geneset analysis using a modified two-way ANOVA procedure, and to detect genesets that current methods fail to detect.

Analysis of Functional and Anatomic Success Following Endonasal Dacryocystorhinostomy

Objectives: The aim of this study was to assess the concomitant perioperative procedures, the causes of nasolacrimal duct obstruction, the success rate, and the complications associated with endonasal dacryocystorhinostomy (ENDCR).Methods: In this single-center retrospective study, 98 patients underwent 104 ENDCRs between January 1994 and February 2006. There were 78 patients with 84 nasolacrimal duct obstructions who were included in this study.Results: The overall functional success rate with improvement in symptoms was 94.9% for primary surgery (59 of 84 obstructions) and 63.6% for salvage surgery after failure of primary surgery performed in another hospital (25 of 84 obstructions). The mean follow-up time was 36.8 +/- 17.11 months. Primary surgery showed better results, with a complete success rate of 93.2%, than did salvage surgery, with a success rate of only 68%. Persistent symptoms, despite an open rhinostomy, were found in 1.7% of patients with primary surgery and in 12% of those with salvage surgery. Failure of ENDCR was observed in 3.4% of patients after primary surgery and in 20% after salvage surgery. We encountered only minimal perioperative complications, and these were essentially related to lacrimal intubation.Conclusions: Because of the possibility of treating concomitant sinonasal disorders, the cosmetic advantages, and the excellent results, ENDCR represents the procedure of choice for treating nasolacrimal duct obstructions. The main challenge lies in the exact preoperative assessment, as well as postoperative evaluation in case of failure.

A new all-round density functional based on spin states and SN2 barriers

We report here a new empirical density functional that is constructed based on the performance of OPBE and PBE for spin states and SN 2 reaction barriers and how these are affected by different regions of the reduced gradient expansion. In a previous study [Swart, Sol̀, and Bickelhaupt, J. Comput. Methods Sci. Eng. 9, 69 (2009)] we already reported how, by switching between OPBE and PBE, one could obtain both the good performance of OPBE for spin states and reaction barriers and that of PBE for weak interactions within one and the same (SSB-sw) functional. Here we fine tuned this functional and include a portion of the KT functional and Grimme's dispersion correction to account for π- π stacking. Our new SSB-D functional is found to be a clear improvement and functions very well for biological applications (hydrogen bonding, π -π stacking, spin-state splittings, accuracy of geometries, reaction barriers)

Exploring chromium (VI) dioxodihalides chemistry: is density functional theory the most suitable tool?

A comparative systematic study of the CrO2F2 compound has been performed using different conventional ab initio methodologies and density functional procedures. Two points have been analyzed: first, the accuracy of results yielded by each method under study, and second, the computational cost required to reach such results. Weighing up both aspects, density functional theory has been found to be more appropriate than the Hartree-Fock (HF) and the analyzed post-HF methods. Hence, the structural characterization and spectroscopic elucidation of the full CrO2X2 series (X=F,Cl,Br,I) has been done at this level of theory. Emphasis has been given to the unknown CrO2I2 species, and specially to the UV/visible spectra of all four compounds. Furthermore, a topological analysis in terms of charge density distributions has revealed why the valence shell electron pair repulsion model fails in predicting the molecular shape of such CrO2X2 complexes

Autologous adult cortical cell transplantation enhances functional recovery following unilateral lesion of motor cortex in primates: a pilot study.

BACKGROUND:: Although cell therapy is a promising approach after cerebral cortex lesion, few studies assess quantitatively its behavioral gain in non-human primates. Furthermore, implantations of fetal grafts of exogenous stem cells are limited by safety and ethical issues. OBJECTIVE:: To test in non-human primates the transplantation of autologous adult neural progenitor cortical cells with assessment of functional outcome. METHODS:: Seven adult macaque monkeys were trained to perform a manual dexterity task, before the hand representation in motor cortex was chemically lesioned unilaterally. Five monkeys were used as control, compared to two monkeys subjected to different autologous cells transplantation protocols performed at different time intervals. RESULTS:: After lesion, there was a complete loss of manual dexterity in the contralesional hand. The five "control" monkeys recovered progressively and spontaneously part of their manual dexterity, reaching a unique and definitive plateau of recovery, ranging from 38% to 98% of pre-lesion score after 10 to 120 days. The two "treated" monkeys reached a first spontaneous recovery plateau at about 25 and 40 days post-lesion, representing 35% and 61% of the pre-lesion performance, respectively. In contrast to the controls, a second recovery plateau took place 2-3 months after cell transplantation, corresponding to an additional enhancement of functional recovery, representing 24 and 37% improvement, respectively. CONCLUSIONS:: These pilot data, derived from two monkeys treated differently, suggest that, in the present experimental conditions, autologous adult brain progenitor cell transplantation in non-human primate is safe and promotes enhancement of functional recovery.

Functional dynamics of PDZ binding domains: a normal-mode analysis.

Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80-120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events.

Topological comparison of methods for predicting transcriptional cooperativity in yeast

Background: The cooperative interaction between transcription factors has a decisive role in the control of the fate of the eukaryotic cell. Computational approaches for characterizing cooperative transcription factors in yeast, however, are based on different rationales and provide a low overlap between their results. Because the wealth of information contained in protein interaction networks and regulatory networks has proven highly effective in elucidating functional relationships between proteins, we compared different sets of cooperative transcription factor pairs (predicted by four different computational methods) within the frame of those networks. Results: Our results show that the overlap between the sets of cooperative transcription factors predicted by the different methods is low yet significant. Cooperative transcription factors predicted by all methods are closer and more clustered in the protein interaction network than expected by chance. On the other hand, members of a cooperative transcription factor pair neither seemed to regulate each other nor shared similar regulatory inputs, although they do regulate similar groups of target genes. Conclusion: Despite the different definitions of transcriptional cooperativity and the different computational approaches used to characterize cooperativity between transcription factors, the analysis of their roles in the framework of the protein interaction network and the regulatory network indicates a common denominator for the predictions under study. The knowledge of the shared topological properties of cooperative transcription factor pairs in both networks can be useful not only for designing better prediction methods but also for better understanding the complexities of transcriptional control in eukaryotes.

Asymmetry of Functional Connectivity in Schizophrenia at Different Spatial Scales

Introduction: The interhemispheric asymmetries that originate from connectivity-related structuring of the cerebral cortex are compromised in schizophrenia (SZ). Recently, we have revealed the whole-head topography of EEG synchronization in SZ (Jalili et al. 2007; Knyazeva et al. 2008). Here we extended the analysis to assess the abnormality in the asymmetry of synchronization, which is further motivated by the evidence that the interhemispheric asymmetries suspected to be abnormal in SZ originate from the connectivity-related structuring of the cortex. Methods: Thirteen right-handed SZ patients and thirteen matched controls, participated in this study and the multichannel (128) EEGs were recorded for 3-5 minutes at rest. Then, Laplacian EEG (LEEG) were calculated using a 2-D spline. The LEEGs were analysis through calculating the power spectral density using Welch's average periodogram method. Furthermore, using a state-space based multivariate synchronization measure, S-estimator, we analyzed the correlate of the functional cortico-cortical connectivity in SZ patients compared to the controls. The values of S-estimator were obtained at three different special scales: first-order neighbors for each sensor location, second-order neighbors, and the whole hemisphere. The synchronization measures based on LEEG of alpha and beta bands were applied and tuned to various spatial scales including local, intraregional, and long-distance levels. To assess the between-group differences, we used a permutation version of Hotelling's T2 test. For correlation analysis, Spearman Rank Correlation was calculated. Results: Compared to the controls, who had rightward asymmetry at a local level (LEEG power), rightward anterior and leftward posterior asymmetries at an intraregional level (first- and second-order S-estimator), and rightward global asymmetry (hemispheric S-estimator), SZ patients showed generally attenuated asymmetry, the effect being strongest for intraregional synchronization. This deviation in asymmetry across the anterior-to-posterior axis is consistent with the cerebral form of the so-called Yakovlevian or anticlockwise cerebral torque. Moreover, the negative occipital and positive frontal asymmetry values suggest higher regional synchronization among the left occipital and the right frontal locations relative to their symmetrical counterparts. Correlation analysis linked the posterior intraregional and hemispheric abnormalities to the negative SZ symptoms, whereas the asymmetry of LEEG power appeared to be weakly coupled to clinical ratings. The posterior intraregional abnormalities of asymmetry were shown to increase with the duration of the disease. The tentative links between these findings and gross anatomical asymmetries, including the cerebral torque and gyrification pattern in normal subjects and SZ patients, are discussed. Conclusions: Overall, our findings reveal the abnormalities in the synchronization asymmetry in SZ patients and heavy involvement of the right hemisphere in these abnormalities. These results indicate that anomalous asymmetry of cortico-cortical connections in schizophrenia is amenable to electrophysiological analysis.

Functional MRI evaluation of liver tumour response after radiofrequency: short- and mid-term evolution of diffusion parameters

Purpose: To evaluate the short- and mid-term evolutions of the apparent diffusion coefficient of lesions treated with RF, in order to determine if the ADC can be used as a marker of tumour response. Methods and Materials: Twenty patients were treated for a liver malignancy with RF and were examined on a 1.5 T/3.0 T machine with T2, gadolinium-enhanced T1 and diffusion sequences: before treatment (< 1 month), just after treatment (< 1 month) and midterm (3-6 months). The ADC was measured in the whole lesion and in the area with the most restricted diffusion (MRDA). The ROI size was also measured on the diffusion map. The Pearson/ANOVA tests were used. Results: All patients were successfully treated with complete disappearance of CE. The lesional size on T2 showed a negative evolution in time (p < 0.002). The ADC in the whole lesion showed a bell-shaped evolution (increasing just after RF, then decreasing, p = 0.02). The ROI size on the diffusion map followed a similar course (p = 0.01). For the MRDA, such evolutions were also found, but they were not significant. There was a negative correlation between CE and the ADC (p < 0.02) and between the lesional size on T2 and ADC (p = 0.03) in the whole lesion. There were also positive correlations between the ROI size and ADC (p = 0.0008) and between CE and the size on T2 (p = 0.0002). The ADC in MRDA showed some non-significant correlations with other variables. Conclusion: The lesions successfully treated with RF have a clear and predictable evolution in terms of T2 size, CE and ADC.

Examining the Agreement of Structural Loss Measured With Heidelberg Retinal Tomograhy and Functional Loss With Standard Automated Perimetry (SAP; Octopus), Pulsar Perimetry (PP), and Moorfields Motion Displacement Test (MDT) Perimetry

Purpose: To examine the relationship of functional measurements with structural measures. Methods: 146 eyes of 83 test subjects underwent Heidelberg Retinal Tomography (HRTIII) (disc area<2.43, mphsd<40), and perimetry testing with Octopus (SAP; Dynamic), Pulsar (PP; TOP) and Moorfields MDT (ESTA). Glaucoma was defined as progressive structural or functional loss (20 eyes). Perimetry test points were grouped into 6 sectors based on the estimated optic nerve head angle into which the associated nerve fiber bundle enters (Garway-Heath map). Perimetry summary measures (PSM) (MD SAP/ MD PP/ PTD MDT) were calculated from the average total deviation of each measured threshold from the normal for each sector. We calculated the 95% significance level of the sectorial PSM from the respective normative data. We calculated the percentage agreement with group1 (G1), healthy on HRT and within normal perimetric limits, and group 2 (G2), abnormal on HRT and outside normal perimetric limits. We also examined the relationship of PSM and rim area (RA) in those sectors classified as abnormal by MRA (Moorfields Regression Analysis) of HRT. Results: The mean age was 65 (range= [37, 89]). The global sensitivity versus specificity of each instrument in detecting glaucomatous eyes was: MDT 80% vs. 88%, SAP 80% vs. 80%, PP 70% vs. 89% and HRT 80% vs. 79%. Highest percentage agreement of HRT (respectively G1, G2, sector) with PSM were MDT (89%, 57%, nasal superior), SAP (83%, 74%, temporal superior), PP (74%, 63%, nasal superior). Globally percentage agreement (respectively G1, G2) was MDT (92%, 28%), SAP (87%, 40%) and PP (77%, 49%). Linear regression showed there was no significant trend globally associating RA and PSM. However, sectorally the supero-nasal sector had a statistically significant (p<0.001) trend with each instrument, the associated r2 coefficients are (MDT 0.38 SAP 0.56 and PP 0.39). Conclusions: There were no significant differences in global sensitivity or specificity between instruments. Structure-function relationships varied significantly between instruments and were consistently strongest supero-nasally. Further studies are required to investigate these relationships in detail.

Focal dependent pleural thickening at MDCT: pleural lesion or functional abnormality?

PURPOSE: To describe the characteristics of reversible focal pleural thickenings (PTs) mimicking real plaques, that firstly suggest asbestos exposure or pleural metastasis; to propose an imaging strategy and propose an explanation for their mechanism of formation. PATIENTS AND METHODS: Retrospective review of data from 19 patients with PTs fitting the description of pleural plaques at chest computed tomography (CT) and presenting modifications (clearance or appearance) of at least one PT at an additional chest examination in prone position. RESULTS: A total of 152 PTs were recorded on the first chest CT examinations with a range of two to 19 pleural opacities per patient. All PTs had a posterior distribution in the lower lobes. On the additional acquisitions, 144 PTs disappeared. Seventeen patients presented complete regression of PTs and two patients presented persistence of eight PTs. CONCLUSION: Additional low dose acquisition in prone position should be performed in all patients presenting with focal PT in a dependent and basal location. This may allow to exclude a pleural plaque in case of asbestos exposure but also a pleural metastasis in oncologic patients. These reversible dependent PTs could be related to physiological focal accumulation of lymphatic fluid in subpleural area.

The molecular basis of social behavior: models, methods and advances.

Elucidating the molecular and neural basis of complex social behaviors such as communal living, division of labor and warfare requires model organisms that exhibit these multi-faceted behavioral phenotypes. Social insects, such as ants, bees, wasps and termites, are attractive models to address this problem, with rich ecological and ethological foundations. However, their atypical systems of reproduction have hindered application of classical genetic approaches. In this review, we discuss how recent advances in social insect genomics, transcriptomics, and functional manipulations have enhanced our ability to observe and perturb gene expression, physiology and behavior in these species. Such developments begin to provide an integrated view of the molecular and cellular underpinnings of complex social behavior.