Electrophysiological correlates of recollecting faces of known and unknown individuals

We recorded brain potentials from healthy human subjects during a recognition test in order to monitor neural processing associated with face recollection. Subjects first attempted to memorize 40 faces; half were accompanied by a voice simulating that person speaking (e.g., "I'm Jimmy and I was a roadie for the Grateful Dead") and half were presented in silence. In the test phase, subjects attempted to discriminate both types of old faces (i.e., "named" and "unnamed" faces) from new faces. Recognition averaged 87% correct for named faces, 74% correct for unnamed faces, and 91% correct for new faces. Potentials to old faces were more positive than those to new faces from 300 to 600 ms after face onset. For named faces, the old-new ERP difference was observed at anterior and posterior scalp locations. For unnamed faces, the old-new ERP difference was observed only at posterior scalp locations. Results from a prior experiment suggest that these effects do not reflect perceptual priming of faces. The posterior portion of the old-new ERP difference was thus interpreted as a neural correlate of retrieval of visual face information and the anterior portion as an indication of retrieval of person-specific semantic information.     

Health care technology assessment: implications for modern medical practice. Part I. Understanding technology adoption and analyses

In the modern era of rapidly rising medical costs, health care technology assessment--multidisciplinary evaluation of clinical and economic aspects of technology--has assumed an increasingly important role in health policy and clinical decision-making. This review examines health care technology adoption, its impact on medical and surgical practice, and recent trends in health care technology assessment. Part I discusses the difficult challenges posed by assessment and provides a guide to the methodologies used.     

Ankle fusion for definitive management of non-reconstructable pilon fractures

BACKGROUND: Highly comminuted pilon fractures, especially with a compromised soft tissue envelope, present a challenging treatment scenario. This study presents our results for patients managed with ankle fusion rather than ORIF. MATERIALS AND METHODS: Fourteen patients with ankle joint incongruence after non-reconstructable tibia pilon fractures were treated with primary tibiotalar arthrodesis using a fixed-angle cannulated blade plate. Delayed metaphyseal unions due to bone defects were treated concurrently. The subtalar joint was preserved in all cases. RESULTS: Metaphyseal healing and stable arthrodesis was obtained in each case. There was one case of blade plate breakage in a patient who still achieved successful arthrodesis without reoperation. Union was achieved at an average of 15 weeks. No secondary procedures were required to obtain union. All 14 patients were ambulatory at last followup. Average followup was 39 weeks. CONCLUSION: Primary ankle arthrodesis can be achieved using a cannulated blade plate to address a non-reconstructable articular surface and metaphyseal bone defects in complex tibia pilon fractures.     

High incidence of glucose-6-phosphate dehydrogenase deficiency in Croatian island isolate: example from Vis island, Croatia

Aim

To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the population of the town of Komiža on the island of Vis, which has previously been reported as a place with several cases of favism.

Methods

We screened 302 randomly selected men, using the fluorescent spot test. Fluorescence readings were performed at the beginning and 5, 10, and 20 minutes after incubation, and were classified into three groups: bright fluorescence, weak fluorescence, and no fluorescence. All men found to be G6PD deficient were tested with a quantitative spectrophotometric UV method.

Results

Of the 302 tested blood samples, 36 (11.9%) samples showed weak fluorescence or no fluorescence spots. Spectrophotometric UV test showed that 18 (5.96%) men were G6PD deficient. The prevalence of G6PD deficiency in the population of Komiža is significantly higher (P<0.001) than the prevalence in the whole population of Dalmatia in the south of Croatia (0.75% in men).

Conclusion

On the basis of these findings, we recommend including the newborns from the island of Vis into a screening program for G6PD deficiency. Our results indicate that G6PD deficiency should be determined for all the island isolates in the Mediterranean basin and they warrant further studies.Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common inherited disorders, with approximately 400 million people affected worldwide (1,2). More than 140 different mutations of the G6PD gene have been identified (3). Molecular analysis of the inhabitants of the Dalmatian region in the south of Croatia identified the G6PD Cosenza (1376 G→C) as the most frequent mutation, followed by G6PD Mediterranean mutation (563 C→T, ref. (4). All individuals with G6PD Mediterranean mutation had concomitant silent C→T transition at the position 1311, which is often found in Mediterranean basin, but not in Asia (5). Association of the factor V Leiden and G6PD deficiency has been observed in Dalmatian population (6).Glucose-6-phosphate dehydrogenase deficiency is unrecognized in most affected individuals. However, it may have a clinical expression such as acute acquired hemolytic anemia, chronic nonspherocytic hemolytic anemia, favism, and neonatal hyperbilirubinemia (7). Different variants of the enzyme are found in high frequency in African, Mediterranean, and Asian populations (8). Heterozygote advantage against malaria was found to account for the high frequency of distinct alleles in particular populations (9).Komiža is a small town on the isolated island of Vis, in the Adriatic Sea, a part of the Mediterranean basin. Although the prevalence of G6PD deficiency has not previously been determined in Komiža, there were several cases of favism originating from Komiža which were treated in our hospital. Therefore, we hypothesized that there could be a significantly higher incidence of G6PD deficiency than in other parts of Dalmatia.The aim of this study was to determine the prevalence of G6PD deficiency in the population of Komiža and compare it with the prevalence of G6PD deficiency in the whole population of Dalmatia. Being an X-linked genetic condition, the prevalence of G6PD deficiency in any given population is determined by the number of men with the deficiency (10).     

Loxoribine,a selective Toll-like receptor 7 agonist,induces maturation of human monocyte-derived dendritic cells and stimulates their Th-1- and Th-17-polarizing capability

Recently, a guanosine analog, 7-allyl-7,8-dihydro-8-oxo-guanosine (loxoribine), has been identified as a selective Toll-like receptor (TLR)7 agonist. Bearing in mind the controversy regarding the expression of TLR7 by human myeloid dendritic cells (DCs) and its significance for functions of these cells, the goal of this study was to investigate the effect of loxoribine on differentiation, maturation and functions of human monocyte-derived (Mo)DCs. Immature MoDCs were obtained by cultivation of monocytes for 6 days with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. These cells were stimulated with loxoribine (250 μM) for an additional 48 h. Phenotypic properties of MoDCs were determined by flow cytometry, cytokine production was assayed by ELISA, whereas their allostimulatory capability was tested using a mixed leukocyte reaction. We showed that loxoribine up-regulated the expression of TLR7, CD40, CD54, CD80, CD83 and CCR7 and stimulated the production of IL-12, IL-23, IL-27 and IL-10 by MoDCs, whereas the level of interferon (IFN)-β was not modulated. Allogeneic CD4⁺T cells in co-culture with loxoribine-treated MoDCs proliferated more strongly, at lower DC/CD4⁺T-cell ratio (1:80), and secreted significantly higher levels of IL-17 and IFN-γ compared to the cultures with control MoDCs. The stimulatory effect of loxoribine on T helper (Th)1 polarization capability of MoDCs was further potentiated by ligation of CD40. In conclusion, our results show that loxoribine stimulated differentiation, maturation, allostimulatory as well as Th1 and Th17 polarization capability of human MoDCs and suggests that these effects might be associated with up-regulation of TLR7 expression, but not increased IFN-β production.     

Apoptotic and anti-apoptotic factors in early human mandible development

The regulators of apoptosis Bcl-2, Bax, caspase-3, p53, and Hsp70 were analyzed immunohistochemically in the developing human mandible of eight human conceptuses from weeks 5 to 10 of gestation. During this period, all proteins displayed an increased pattern of expression in the mandible ectomesenchyme and in newly formed bone, except for caspase-3, which showed decreased expression in the ectomesenchyme, but appeared first in the ossification zone at the 7th wk of development. Simultaneously, the oral epithelium showed weak (p53) to strong (hsp70) expression of all proteins investigated, while in Meckel's cartilage cells, bcl-2 was expressed weakly and hsp70 was expressed moderately. Cells on the surface of the forming bone were predominantly bax positive, and only occasionally bcl-2 positive. Only a few cells on the surface and inside the bony spicules co-expressed bax and bcl-2. Terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick-end labelling (TUNEL)-positive cells were found to be apoptotic osteoblasts. The expression of all proteins investigated changed dynamically during early mandible development and the subsequent differentiation of Meckel's cartilage and bone. While interactions between those factors might be associated with the survival of Meckel's cartilage, in the ossification zone they might participate in the control of cell numbers, mineralization, and bone remodelling. Among many other factors, precise orchestration of pro- and anti-apoptotic factors contributes to normal mandible development.     

Executive Summary: Value-based Purchasing and Technology Assessment in Orthopaedics

As US healthcare expenditures continue to rise, reform has shifted from spending controls to value-based purchasing. This paradigm shift is a drastic change on how health care is delivered and reimbursed. For the shift to work, policymakers and physicians must restructure the present system by using initiatives such as process reengineering, insurance and payment reforms, physician reeducation, data and quality measurements, and technology assessments. Value, as defined in economic terms, will be a critical concept in modern healthcare reform. We summarize the conclusions of this ABJS Carl T. Brighton Workshop on healthcare reform.     

Evidence of hypercoagulability and inflammation in young patients long after acute cerebral ischaemia

INTRODUCTION: Young subjects with acute cerebral ischaemia - stroke or transient ischaemic attack - form an etiologically heterogeneous and often not clearly explained group of patients. The aim was to investigate possible disturbances in haemostasis and inflammation long after an acute cerebral ischaemic event. MATERIALS AND METHODS: Forty-four consecutive patients referred after having suffered from acute cerebral ischaemia before the age of 45 participated 1 to 9 years (median value 5 years) after the event. At the time of blood sampling 33 (75%) patients were receiving antithrombotic treatment. Forty-six apparently healthy subjects of the same age group served as controls. In all subjects global haemostasis parameters (overall haemostasis, coagulation and fibrinolytic potential), thrombophilia, several markers of haemostasis activation and inflammation were determined. RESULTS: Patients did not differ from controls in most of the conventional risk factors and the presence of most forms of thrombophilia, although in seven (17.5%) patients the weak presence of lupus anticoagulants was observed. Patients had significantly increased overall haemostasis and coagulation potential, increased soluble P-selectin and D-dimer, decreased overall fibrinolysis potential and increased fibrinogen and C-reactive protein compared to controls. The subgroups of patients receiving antiplatelet treatment, with thrombophilia and recurrent acute cerebral ischaemia, did not differ significantly from the other patients. CONCLUSIONS: In young patients long after acute cerebral ischaemia an imbalance in the haemostatic system and a minor, but significant degree of inflammation was detected. The mechanisms behind haemostatic imbalance seem to be enhanced thrombin generation, platelet activation and depressed fibrinolysis.     

Differentiating morphology, form, and meaning: neural correlates of morphological complexity

The role of morphological structure in word recognition raises issues about the nature and structure of the language system. One major issue is whether morphological factors provide an independent principle for lexical organization and processing, or whether morphological effects can be reduced to the joint contribution of form and meaning. The independence of form, meaning, and morphological structure can be directly investigated using derivationally complex words, because derived words can share form but need not share meaning (e.g., archer-arch). We used an event-related functional magnetic resonance imaging paradigm to investigate priming between pairs of words that potentially shared a stem, where this link was either semantically transparent (e.g., bravely-brave) or opaque (e.g., archer-arch). These morphologically related pairs were contrasted with identity priming (e.g., mist-mist) and priming for pairs of words that shared only form (e.g., scandal-scan) or meaning (e.g., accuse-blame). Morphologically related words produced significantly reduced activation in left frontal regions, whether the pairs were semantically transparent or opaque. The effect was not found for any of the control conditions (identity, form, or meaning). Morphological effects were observed separately from processing form and meaning and we propose that they reflect segmentation of complex derived words, a process triggered by surface morphological structure of complex words.     

From the Cover: Accumulation of driver and passenger mutations during tumor progression

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development—providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small—0.004 ± 0.0004—and has major implications for experimental cancer research.