In this study, we used a substance P (SP) immunohistochemical method to analyze the expression localization of osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) in giant cell tumor (GCT) of the bone, and to detect the clinical significance of their expression. The data showed that the positive expression rate of OPG in the multinucleated giant cells (MGCs) and stromal cells (STCs) of GCT was 80.65 and 74.19%, respectively. The positive expression rate of OPG in MGCs was correlated with age and prognosis (P<0.05), but not in STCs. The strength of positive OPG expression in MGCs and STCs was negatively correlated with prognosis . The positive expression rate of OPGL in the MGCs and STCs was 41.94 and 67.74%, respectively. The positive expression rate of OPGL in the MGCs was correlated with age and prognosis (P<0.05); the strength of OPGL expression in MGCs was positively correlated with Campanicci’s grade and recurrence. Additionally, the positive expression rate of OPGL in STCs was correlated with age and Jaffe’s grade (P<0.05). The strength of OPGL expression in STCs was negatively correlated with Jaffe’s grade . In conclusion, OPG and OPGL are expressed in MGCs and STCs in GCT of the bone. The invasion of tumor cells was positively correlated with OPGL in MGCs, which confirmed that MGCs participate in the process of osteolytic destruction of GCT of bone. Giant cell tumor (GCT) of the bone is an osteolytic tumor that is potentially malignant or is between benign and malignant, and is characterized by local invasive destruction of bone  and a hiThe present study included 18 male and 13 female patients with an average age of 35.19 years . The study was approved by the Ethics Committee of the Orthopedic Department, The General Hospital of Jinan Militray Commanding Region, Jinan, Shandong, China. Written informed consent was obtained from the patients and patient’s family. Of the 31 patients, there were 9 cases of distal femur tumor, 9 cases of proximal tibia, 4 cases of proximal femur, 3 cases of proximal humerus, 2 cases of iliac, 1 case of distal radius, 1 case of distal ulna, 1 case of pubis and 1 case of calcaneus. According to Jaffe’s classification criteria, there were 12 cases of class I, 17 cases of class II and 2 cases of class III tumors. Based on Campanicci’s radiological classification criteria, there were 7 cases of class I, 16 cases of class II and 8 cases of class III tumors. All patients were treated with tumor curettage and bone grafting surgeries performed by the same surgical group.All 31 patients received follow-up surveys for an average duration of 76 months . No metastasis was observed. Eight patients exhibited recurrence, and the second surgery included 1 case of tumor curettage and bone grafting, 4 cases of tumor resection and prosthesis replacement, 1 case of tumor resection and inactivated replantation,and 1 case of extended tumor resection. Following secondary surgery, the 8 patients received follow-up for an average duration of 50 months , and no metastasis or recurrence was observed.Polyclonal rabbit anti-human antibodies specific for OPG and OPGL were purchased from Boshide . The substance P  immunohistochemistry kit was purchased from Zhongshanjingqiao Biotechnical Co., Ltd. .μm for H&E staining and OPG/OPGL analysis. All methods were performed according to the manufacturer’s instructions. The slice with positive expression was used as the positive control. The negative control was established with the primary antibody replaced by phosphate-buffered saline (PBS).H&E-stained slices of the 31 GCT pathological specimens were reviewed and typical paraffin-embedded samples were selected for analysis. The 31 representative samples were used to prepare 3 paraffin sections with a thickness of 4 Both OPG and OPGL were expressed in stromal cells (STCs) and multinucleated giant cells (MGCs). Positive expression was determined by yellow, brown and tan particles on the plasma membrane or in the cytosol –5. The sThe Wilcoxon rank-sum test, Kruskal-Wallis H test and Spearman’s correlation method were used to analyze the correlation of the OPG and OPGL expression levels with age, gender, tumor site, Jaffe’s class, Campanicci’s class and prognosis. All data analysis was performed using SPSS 17.0 software . P<0.05 was considered to indicate a statistically significant difference.Of the 31 cases of GCT, 25 exhibited positive OPG expression in the MGCs, and 6 demonstrated negative expression. The OPG positive expression rate was 80.65%. Further analysis revealed that the expression of OPG in the MGCs was not correlated with gender, tumor site, Jaffe’s class or Campanicci’s class (P>0.05). The patients between 21 and 40 years demonstrated a positive rate of 94.74%, which was significantly higher than that of the other two age groups (P<0.05). Notably, the expression of OPG in the MGCs was correlated with recurrence P<0.05; .Of the 31 cases of GCT, 23 demonstrated positive OPG expression in the STCs, and 8 exhibited negative expression. The OPG positive expression rate was 74.19%. Further analysis revealed that the expression of OPG in the STCs was not correlated with gender, age, tumor site, Jaffe’s class, Campanicci’s class or prognosis P>0.05; .The Spearman’s analysis revealed that the expression of OPG in the MGCs and the STCs was not correlated with gender, age, tumor site, Jaffe’s class or Campanicci’s class (P>0.05); however, it was negatively correlated with prognosis .Of the 31 cases of GCT, 13 demonstrated positive OPGL expression in the MGCs, and 18 had negative expression. The OPG positive expression rate was 41.94%. Further analysis revealed that the expression of OPGL in the MGCs was not correlated with gender, tumor site, Jaffe’s class or Campanicci’s class (P>0.05). The patients <20 years demonstrated a positive rate of 100%, which was significantly higher than that of the other two age groups (P<0.05). Notably, the expression of OPGL in the MGCs was correlated with recurrence P<0.05; .Of the 31 cases of GCT, 21 exhibited positive OPGL expression in the STCs, and 10 demonstrated negative expression. The OPG-positive rate was 67.74%. Further analysis revealed that the expression of OPGL in the STCs was not correlated with gender, tumor site, Campanicci’s class or prognosis (P>0.05). The patients between 21 and 40 years demonstrated a positive rate of 84.21%, which was significantly higher than that of the other two age groups (P<0.05). Importantly, the OPGL positive expression rate was significantly higher in the Jaffe’s class I group (91.67%) than in the Jaffe’s class II and III groups P<0.05; .The Spearman’s analysis revealed that the expression of OPGL in the MGCs was not correlated with gender, age, tumor site, Jaffe’s class or prognosis (P>0.05), but it was positively correlated with Campanicci’s class . The expression of OPGL in the STCs was not correlated with gender, age, tumor site, Campanicci’s class or prognosis (P>0.05), but it was negatively correlated with Jaffe’s class .en bloc or wide resection. Intralesional excision has been used as the primary approach for the treatment of GCT, but the recurrence rate is as high as 20–50%. Wide excision is able to reduce the recurrence rate, but the frequent occurrence of long-term complications reduces the clinical efficacy. Although the development of bisphosphonate drugs has provided a potent method for retaining the joints of the patients and for improving the clinical efficacy, limited information is available regarding the mechanisms underlying the effects of these drugs. In the present study, we retrospectively analyzed 31 patients with complete clinical data for the past 10 years to provide scientific evidence for the clinical use of bisphosphonate drugs. We investigated the expression of OPG and OPGL in the GCTs using immunohistochemical analysis, to explore the correlation between their expression and the clinical characteristics of the tumor.GCT is a common type of primary bone tumor and accounts for 5–8% of the incidence of bone tumors. GCT commonly occurs in 20 to 50-year-old individuals, and is mostly focused on the metaphysis, particularly around the knee (∼65%). The invasion of the GCT is mainly due to the osteolytic destruction of the local bone. At present, the major surgical approaches for GCT treatment include intralesional excision and OPG is a soluble protein secreted by osteoblasts and bone marrow stromal cells. OPG is also a decoy receptor, with OPGL  as its ligand. By binding to the RANKL secreted by the bone marrow stromal cells, OPG blocks the interaction between RANKL and RANK, and subsequently acts to inhibit the differentiation of osteoclasts and the bone resorption activity of mature osteoclasts. In this way, OPG is able to induce the apoptosis of osteoclasts, reduce bone resorption and protect the bone. In addition, OPG is a member of the TNF receptor superfamily, and is capable of binding to TNF ligands.RANKL is mainly expressed in osteoblasts and bone marrow stromal cells. RANKL binds to the plasma membrane, and is subsequently localized on the surface of osteoblasts and bone marrow stromal cells. The receptor of RANKL is RANK, which is usually localized to the surface of osteoclast precursors. In the presence of macrophage colony stimulating factor (M-CSF), when the osteoclast precursors and osteoblasts or bone marrow stromal cells come into contact with each other, RANKL binds to RANK on the surface of the osteoclasts and subsequently induces the activation and differentiation of the osteoclasts through the intracellular signaling pathway. RANKL can simultaneously enhance the activity of the mature osteoclasts and prevent osteoclast apoptosis. Therefore, bone destruction caused by RANKL-mediated osteoclast activation is necessary for the invasive growth of tumors.et al than in the other two age groups (P<0.05). The positive rate of OPGL in the STCs was significantly higher in the 21 to 40-year-old patient group (84.21%) than in the other two age groups (P<0.05). The positive rate of OPGL in the MGCs was significantly higher in the ≤20-year-old patient group (100.00%) than in the other two age groups (P<0.05). These results indicated that the MGCs were the main cause of bone destruction during the course of the GCT before the age of 20 years, while the STCs were the key reason for the bone destruction between the ages of 21 and 40 years.Secondly, the expression of OPG and OPGL in different types of cells in the GCT was able to affect the prognosis. The positive rate of OPG in the MGCs was significantly higher for the non-recurrence group (91.30%) than for the recurrence group . The expression level of OPG in the MGCs and STCs was negatively correlated with prognosis . Notably, the higher the OPG expression level in the MGCs and STCs, the higher the recurrence probability observed. The positive rate of OPGL in the MGCs was significantly higher for the recurrence group than for the non-recurrence group (P<0.05), indicating that the expression of OPG in the MGCs may be used as an important indicator for the prognosis.et al than in the Jaffe’s class II and III GCT (P<0.05). In the MGCs, the expression level of OPGL was positively correlated with Campanicci’s classification ; whereas in the STCs, the expression level of OPGL was negatively correlated to the Jaffe’s classification . These results indicated that MGCs and STCs have different biological functions. Although it has been suggested that GCT is mainly composed of STCs and the MGCs are only responsive cells, the origin, properties and functions of MGCs remain unclear. It has been suggested that MGCs play the role of osteoclasts. Thompson et al proposed al(et al, found tg system .


In Table 6, a unit conversion problem has resulted in incorrect table values. Please find a correct version of the table here: Necessary corrections to the text are as follows:There is an error in the sixth sentence of the "Methods and Findings" portion of the Abstract. The correct sentence reads: The absolute rate of wasting was 1.59 events per child-year (503 events/315.3 child-year) in the intervention group and 1.78 events per child-year (322 events/180.4 child-year) in the comparison group.There is an error in the first sentence of the fourth paragraph of the Results section. The correct sentence reads: The absolute rate of wasting was 1.59 events per child-year  in the intervention group and 1.78 events per child-year  in the comparison group.The first sentence of the fifth paragraph of the results section should reference Table 6 in place of Table 4. The correct sentence reads: Mortality was lower for children whose households were in the intervention group than those who were not  (Table 6).There is an error in the eighth sentence of the fourth paragraph of the Discussion section. The correct sentence reads: It is important to note that the population was under very severe stress with mortality rates when expressed in conventional emergency terms of 1.7/10,000/d for the intervention group and 2.9/10,000/d for the comparison group.


Few investigations have been done to analyze the level of evidence in journals related to hand surgery, compared to other related research fields. The objective of this study was to assess the level of evidence of the clinical research papers published in the Ibero-american (RICMA), the European (JHSE) and American (JHSA) Journals of Hand Surgery.2) test for categorical variables with a significance level of 0.05.A total of 932 clinical research papers published between 2005 and 2009  were reviewed. Two independent observers classified the level of evidence based on the Oxford International Classification, 5 being the lowest level and 1 the highest level. The observed frequencies of the level of evidence for each journal were compared with the expected frequencies by a chi-square .Inter-observer agreement analysis showed a Kappa of 0.617. Intra-observer agreement analysis presented a Kappa of 0.66 for the observer 1, and a Kappa of 0.751 for the observer 2. More than 80% of the papers in RICMA and JHSE and a 67.6% in the JHSA presented a level of 4. No level 1 or 2 studies were published in RICMA, compared to JHSE (0.9% level 1 and 5.0% level 2) and JHSA (8.3% level 1 and 10% level 2). The percentage of papers with level 3 published in RICMA (16.7%) was higher compared to the JHSE (11.1%) and the JHSA (14.1%). All the results were statistically significant (χThe level of evidence in hand surgery is dependent on the type of journal; being the highest level evidence papers those published in the JHSA, followed by the JHSE and finally the RICMA. Knowing the status of the level of evidence published in hand surgery is the starting point to face the challenges of improving the quality of our clinical research Since the first system for classifying the level of evidence of the clinical research papers was reported, EvidencThe researchers established the null hypothesis (Ho) that the variable “level of scientific evidence” was independent of the variable “type of journal”.Inclusion criteria. All the clinical research articles, which were published between January 2005 and December 2009 in the: Ibero-American Journal of Hand Surgery (RICMA) (“Revista Iberoamericana de Cirugía de la Mano”); The Journal of Hand Surgery European Volume (JHSE) and The Journal of Hand Surgery American Volume (JHSA).Exclusion criteria. Animal studies, anatomical and cadaver studies, basic science studies, instructional course lectures, supplements of abstract, short reports, letters to the editors and review articles were not considered as feasible for the study.Hence, a total of 932 clinical research papers followed the inclusion and exclusion criteria .http://www.cebm.net/index.aspx?o=1025[The articles which met the inclusion and exclusion criteria were randomly assigned to two independent observers , with large clinical experience in hand surgery, and very familiar with Evidence-Based Medicine. An approximate equal number of articles from each journal were assessed by each observer. The level of evidence for each article was assessed based on The Oxford Centre for Evidence-based Medicine - Levels of Evidence (March 2009)Before starting the study, the reliability of the assessment was evaluated based on the analysis of both the intra-observer error and inter-observer error. A random sample of 30 clinical research articles, from a total of 872 papers, published in the English language , were assessed by the two independent observers assigned to the study. After 15 days, a second assessment was undertaken with the order of the articles changed. No papers from the RICMA were included in the sample study for the reliability analysis. This was done so as to avoid information bias[2) test for categorical variables with a significance level of 0.05.For the assessment of the results, the number of articles for each level of evidence rating was expressed as a percentage of the total number of articles meeting the inclusion and exclusion criteria for the period time study. The observed frequencies of the level of evidence for each journal were compared with the expected frequencies using a chi-square  and the null Hypothesis (Ho) was rejected.Inter-observer analysis showed a Kappa of 0.617, with an asymptotic standard error of Kappa (SE) of 0.117. Intra-observer analysis presented a Kappa of 0.66 (SE 0.114) for observer 1, and a Kappa of 0.751 (SE 0.103) for observer 2. All Kappa values were significant (p< 0.001). More than 80% of the papers in the RICMA and the JHSE; and a 67.6% in the JHSA presented a level of 4. Not one of the level 1 and 2 papers was published in the RICMA compared to the JHSE (0.9% level 1 and 5.0% level 2) and the JHSA (8.3% level 1 and 10% level 2). The percentage of papers with level 3, published in the RICMA (16.7%), was higher compared to the JHSE (11.1%) and the JHSA (14.1%) . However, the interpretation of obtained values of kappa is subjective, and different classifications or guides have been proposed to interpret the Kappa coefficient in the reliability analysis. In this paper, the level of agreement in the inter observer and intra observer analysis has shown that a kappa value ranging from 0.617 to 0.751, can be considered as having an excellent to a good level of reliability in the aNot many papers have studied the level of evidence in hand surgery journals or in related research fields, such as orthopaedic and plastic surgery journals. Sinno et al., revieweThe results of this paper demonstrate that most of the clinical articles published in hand surgery, are papers with a very low level of evidence (80% level 4 in the JHSE or RICMA and 67.6% in the JHSA). Most of those papers were case-series and less frequently, poor quality cohort or poor quality case–control studies. Those results were higher compared to orthopaedic journals (48 % level 4 studies), to plasThe percentage of papers with a higher level of evidence (level 1 and 2), was larger in the JHSA (8.3% level 1 and 10% level 2), compared to the RICMA (0%) and the JHSE (0.9% level 1 and 5% level 2). Whilst compared to other journals, there was 21% of level 1 and 15% of level 2 of evidence in orthopaedic journals, 18% of The percentage of papers with level 3 (mostly case- control studies and non-consecutive cohort studies or with very limited population) published in the RICMA (16.7%) was higher compared to the JHSE 11.1%) and the JHSA (14.1%); and similar to other journals: 16% in orthopaedic journals, 16% in .1% and tNo trend analysis is a limitation for this paper, and the information within should be the purpose of further studies, in order to understand how the evidence published in hand surgery journals has changed and how the relationship between changes in the level of evidence and changes in the impact factor index, have also changed over time.After reviewing several articles published in journals from different parts of the world, other questions have arisen. These being, whether the differences that we have found are a reflection of different regional priorities or how the resources used for research have an impact on our findings and even if different countries are the main contributors in high level studies.The level of evidence in hand surgery is dependent on the type of journal; being the highest level evidence papers those published in the JHSA, followed by the JHSE and finally the RICMA. Knowing the status of the level of evidence published in hand surgery is the starting point to face the challenges of improving the quality of our clinical research.There are no financial or non-financial competing interests to declare in relation to this manuscript.RSR was involved as director of the study. He devised and designed the study and was also involved in the analysis and the interpretation of the data. LRB & YMH were the two independent observers involved in the reliability analysis and in the assessment of the level of evidence of papers which followed the inclusion and exclusion criteria. IDLB was involved in the acquisition and analysis of the data, as well as in the drafting and reviewing of the manuscript. All the authors read and approved the final version of the manuscript.


Xenopus laevis, during development. Pax7 expression was first detected in early embryos in the basal plate of prosomere 3, roof and alar plates of prosomere 1 and mesencephalon, and the alar plate of rhombomere 1. As development proceeded, Pax7 cells were observed in the hypothalamus close to the catecholaminergic population of the mammillary region. In the diencephalon, Pax7 was intensely expressed in a portion of the basal plate of prosomere 3, in the roof plate and in scattered cells of the thalamus in prosomere 2, throughout the roof of prosomere 1, and in the commissural and juxtacommissural domains of the pretectum. In the mesencephalon, Pax7 cells were localized in the optic tectum and, to a lesser extent, in the torus semicircularis. The rostral portion of the alar part of rhombomere 1, including the ventricular layer of the cerebellum, expressed Pax7 and, gradually, some of these dorsal cells were observed to populate ventrally the interpeduncular nucleus and the isthmus (rhombomere 0). Additionally, Pax7 positive cells were found in the ventricular zone of the ventral part of the alar plate along the rhombencephalon and the spinal cord. The findings show that the strongly conserved features of Pax7 expression through development shared by amniote vertebrates are also present in the anamniote amphibians as a common characteristic of the brain organization of tetrapods.Pax7 is a member of the highly conserved Pax gene family that is expressed in restricted zones of the central nervous system (CNS) during development, being involved in early brain regionalization and the maintenance of the regional identity. Using sensitive immunohistochemical techniques we have analyzed the spatiotemporal pattern of Pax7 expression in the brain of the anuran amphibian  The development of the central nervous system (CNS) depends on a number of multileveled interactions of products of several large gene families, which act as transcriptional regulators and signaling molecules that guide molecular events in the regional specification, cellular determination and, ultimately, morphohistogenesis. Thus, morphological similarities or differences during vertebrate evolution are determined by the expression of pivotal genes, and related species frequently show common patterns of expression of developmental genes in specific regions of the CNS, supporting their homology  within the diencephalon, mesencephalon, hindbrain and spinal cord in all species studied , and the different developing specimens were obtained by breeding induced by chorionic gonadotropin  and kept in tap water at 20–25°C.For the present study embryos and larvae of nd Faber  and sortnd Faber . All aniAt appropriate times, the animals were deeply anesthetized by immersion in a 0.4 mg/ml solution of tricaine methanesulfonate  and perfused transcardially with 0.9% NaCl, followed by the fixative MEMFA  or 4% paraformaldehyde in 0.1 M phosphate buffer . The brains were dissected out and postfixed approximately 3–4 h in the same fixative solution at 4°C. At early developmental stages, when perfusion was technically impossible (between stages 26 and 47), the whole animal was fixed by immersion and processed. After fixation, the brains were immersed in a solution of 30% sucrose in PB until they sank. For sectioning on a freezing microtome (Thermo Scientific Microm HM 450) the tissue was embedded in a solution of 20% gelatin with 30% sucrose in PB, and stored overnight in a 10% formaldehyde solution with 30% sucrose in PB at 4°C. Brains were then sectioned at 15–30 μm in the transverse, sagittal or horizontal plane. Free-floating sections were collected and rinsed in PB.Immunohistofluorescence procedures were conducted for different primary antibodies, all of which were diluted in 5–10% normal goat serum in PB with 0.1% Triton X-100 (Sigma) and 2% bovine serum albumin . Different protocols were carried out on free-floating sections or in toto (early embryos), with incubation in the primary antibodies for 72 h at 4°C. The dilution of each primary antibody used is detailed in Table 2O2 in PB for 20 min to reduce endogenous peroxidase activity, rinsed again three times in PB, incubated in the primary antibody dilution (mouse anti-Pax7) with 0.025% Triton X-100 in PB, followed by incubation in biotinylated horse anti-mouse , rinsed three times in PB, and visualized by the ABC-DAB kit method .Single-staining protocols for the detection of Pax7 were carried out on the free-floating sections as follows: (1) incubation for 72 h at 4°C in the dilution of the primary serum , at the same dilutions and conditions specified in Table General controls for the immunohistochemical reaction included: (1) western blot analysis; (2) staining some selected sections with preimmune mouse, rabbit, or goat serum instead of the primary antibody; (3) controls in which either the primary and/or the secondary antibody was omitted. In all these negative controls the immunostaining was eliminated. In addition, all the antibodies used have been tested, under identical conditions, in tissues devoid of antigen , as negative control, and in tissues positive for the antigen (rat brain slices at levels expressing the antigen). In all cases the controls were satisfactory.Xenopus laevis showed that all antibodies used labeled a single band, which corresponded well (with minor variations) to the bands labeled in the rat lanes  and that the development of external features makes it easy to characterize distinct stages  just after the animals exhibit the first spontaneous movements. The cells located most rostrally were found in the basal plate of the rostral portion of the diencephalic vesicle, in the prospective p3 Figure . CaudallBy stages 37/38 (about 60 h postfertilization), the intensity and the number of Pax7 positive cells increased, especially in the mz Figures . StronglThe end of the early embryonic period is considered when the mouth of the embryo breaks through . The brain at this stage showed higher numbers of Pax7 cells than in previous stages. The Pax7 cell population in the basal part of p3 was strongly stained, and some cells might extend into basal hypothalamic territories Figure . Pax7 exThe late embryonic stages begin when the tadpoles swim spontaneously, and extend for less than 3 days absorbing the remaining yolk, ending with the independent feeding of the larval tadpole. During the five stages of this period the brain changes considerably and most Pax7 cell populations grow in size and complexity Figures .During this period, the cells located in the basal part of p3 were seen progressively more ventrally  in the hypothalamus  and superficial (lightly labeled cells) layers. Only a few Pax7 cells were detected in the torus semicircularis, where no expression was observed in the vz Figures , 6C,E.In the rhombencephalon, the vz of the alar plate, mainly its ventral part, was positive for Pax7 as a continuation of the ventricular expression found in the mesencephalon, with only a small gap in r0 Figures , 6D,G,H.During prometamorphic stages (approximately 21 days) the development of the hindlimbs and fingers is accomplished. This period ends before the major macroscopic changes that transform the tadpole into a froglet take place. The brain along these stages increases markedly in size and all major subdivisions, anatomical landmarks and main cell populations could be distinguished as in the adult Figures .Xenopus laevis , characterized by the transformation of the tadpole into a juvenile, with the resorption of the tail and change in locomotor behavior, now depending mainly on the limbs. Concerning Pax7 labeling, only a few differences were noted compared with earlier stages, but the segregation of the distinct Pax7 cell populations strikingly increased Figures , 7A–M. I Figures , 7M. Wit Figures ,F, 7F,M. Figures , 7G. The Figures , 7G,H. I Figures , 7I and Xenopus laevis. The present immunohistochemical approach yielded high-resolution staining of cell nuclei from early stages. In similar studies in other species, the use of immunohistochemistry for the detection of the Pax proteins and in situ hybridization for the localization of Pax mRNA resulted in comparable patterns of staining  was identified on the basis on the Pax7 expression  and the rhombomeres 1–8 (r1–8) whose boundaries in developing Xenopus, as described previously in other vertebrates  of r1  expresses Pax7 in the mitotic active vz along the entire rhombencephalon of Xenopus by the presence of the trochlear nucleus, ventrally, and the isthmic nucleus, dorsally  was early identified in Xenopus development, a conspicuous Pax7 cell population is widely distributed in the rostral alar part of r1 (r1r), as in urodeles, birds and mammals  can regenerate their spinal cord after injury  has been related to the capacity of spinal regeneration (Schnapp and Tanaka, Pleurodeles waltl, the lack of Pax7 cells in the vz of the spinal cord in the adult has been related to the lack of regeneration (Joven et al., Xenopus tadpoles, the tail regeneration occurs through the activation of tissue-specific stem and/or progenitor cells, and it has been demonstrated that Pax7 positive satellite cells are required for skeletal muscle regeneration, resembling cellular mechanisms involved in homeostatic and reparative regeneration in mammals (Chen et al., Xenopus tadpoles has been demonstrated to proceed through activation of several genes, such as Sox2, in the vz (Gaete et al., Xenopus laevis can re-establish nerve tracts and achieve functional recovery but this ability is restricted to the larval stages and is lost at the end of metamorphosis (Forehand and Farel, In the embryonic Xenopus and those described for other vertebrates has shown that they are remarkably conserved. The comparison has been readily made using the neuromeric model because the expression of Pax7 in the brain of Xenopus mostly respects the anatomical boundaries described in the current segmental model of organization of the brain. We have observed that Pax7 is first expressed in restricted regions in the vz of the CNS and, as development proceeds, the expression extends from these mitotic germinal zones to migrated cell groups. Such changes have led to suggest different roles for this Pax molecule, and other members of the gene Pax family, in regionalization and subdivision of the nervous system during early stages, and the differentiation of specific cell populations during late stages (Kawakami et al., The comparative study of the expression pattern of Pax7 in the developing CNS of All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Agustín González and Ruth Morona devised the study. Sandra Bandín and to a lesser extent Nerea Moreno, performed all of the experiments. Sandra Bandín and Ruth Morona were the primary contributors to the data analysis. Sandra Bandín and Ruth Morona led the figure preparation and wrote the majority of the article, further completed and edited by Nerea Moreno and Agustín González All authors approved the article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The prediction of gains from selection allows the comparison of breeding methods and selection strategies, although these estimates may be biased. The objective of this study was to investigate the extent of such bias in predicting genetic gain. For this, we simulated 10 cycles of a hypothetical breeding program that involved seven traits, three population classes, three experimental conditions and two breeding methods . Each combination of trait, population, heritability, method and cycle was repeated 10 times. The predicted gains were biased, even when the genetic parameters were estimated without error. Gain from selection in both genders is twice the gain from selection in a single gender only in the absence of dominance. The use of genotypic variance or broad sense heritability in the predictions represented an additional source of bias. Predictions based on additive variance and narrow sense heritability were equivalent, as were predictions based on genotypic variance and broad sense heritability. The predictions based on mass and family selection were suitable for comparing selection strategies, whereas those based on selection within progenies showed the largest bias and lower association with the realized gain. More than two decades ago, Panicum virgatum L.) in high and low yield environments. The predicted gains for dry matter were generally lower in the unfavorable environment. The predicted gain for family selection was superior to that for mass selection. Pinus taeda L.) the predicted direct gain from half-sib selection for rooting ability was 36% while the predicted indirect gain for height at two years was 5.4%. Selecting the best families for height resulted in direct and indirect predicted gains of 8.1% and 14.8%, respectively. The predicted direct gain from full-sib selection for rooting ability was 43% while the predicted indirect gain for height at two years was 9%. Selecting the best families for height yielded direct and indirect predicted gains of 10.1% and 8.6%, respectively. The selection of clones based on rooting ability resulted in a predicted direct gain of 96% associated with a decrease in height. Selecting the best clones for height resulted in direct and indirect predicted gains of 27% and 43%, respectively. Thus, overall, the selection indices assessed resulted in gains for both traits.1 families, respectively, in four years. The real gains were 1.65%/year and 1.75%, respectively, indicating overestimation of the predicted gains. A study with popcorn showed that although there was agreement between the predicted and true mean gains in expansion volume and yield, the predictions per cycle were generally overestimated  of changes in the population mean. stimated . SimilarIn view of the lack of information on the relative importance of possible sources of bias, the aim of this study was to investigate biases in the prediction of genetic gains from selection.M) is calculated as M1 - M, where M1 is the genotypic mean of the bred population and M is the genotypic mean of the population in which the selection was made. The gain is proportional to the difference between the phenotypic mean of the selected population SD), i.e., M1 = M + b.SD. Since the bred population consists of half-sib families whose common parents are the selected individuals, the parameter b should be the same as the regression of the mean phenotypic value of progeny as a function of the difference between the phenotypic value of the selected individual and the phenotypic mean of the base population  (Introducing selection intensity (= SD/σP)  results where 1/2 is the parental control .A = rXY is the coefficient of relationship between X and Y), then the predicted gain in a year is  and the additive genetic value of its relative in the bred population (Y) , h2 is the heritability of the selection unit, where h2 and Since the additive covariance between an individual in the selection unit and its relative in the bred population is only equal to For a single gene and mass selection on only one gender in a population under Hardy-Weinberg equilibrium, the probabilities of the genotypes in the group of selected individuals arep and q are the frequencies of the A1 and A2 alleles in the base population, sH is the intensity of selection against the heterozygote (carrier of the undesirable A2 gene) and sR is the selection intensity against the homozygote for the unfavorable allele. The functionwhere sH and sR values. With no selection , sH = sR = 0 and, therefore, PS = 1.is the proportion of selected individuals, which is a function of the initial gene frequencies and of the The change in the frequency of the favorable gene isThe mean of the improved population ism is the mean of the genotypic values of the homozygotes, a is the deviation between the genotypic value of the homozygote of greater expression and m, d is the deviation between the genotypic value of the heterozygote and m, and M = m + (p - q)a + 2pqd is the mean of the base population (where pulation .The genetic gain due to selection is2 gene with the A1 gene (at) and the proportion of selected individuals (PS)  , thenThe bias in the genetic gain prediction isp2 = 2Δp1. The mean of the bred population isWith mass selection on both genders the change in the frequency of the favorable gene is ΔThus,or,The bias in the prediction of genetic gain isM2/ΔM1 ratio is only equal to two if there is no dominance and, accordingly, only in this situation will the gain from mass selection on the two genders be twice the gain from mass selection on a single gender. Therefore, if dominance is present, then the assumption that selection on both genders results in a predicted gain that is two-fold greater than for selection on only one of the genders is an approximation and a further source of bias.The ΔsH and sR on each gene, together with the selection intensity i, are not known a priori. The same is true for family selection. In the case of half-sib selection with recombination only among individuals of the selected progenies, the alteration in the favorable gene frequency isThe impossibility of using the bias functions to investigate the magnitude of bias must be emphasized since the selection intensities for sD, sH and sR are the selection intensities on the families of common parents A1A1, A1A2 and A2A2.where The mean of the bred population, based on a recombination generation after the selection cycle, isThe genetic gain from among family selection isor,The bias in the genetic gain prediction isThe simulation done here considered seven generic traits, three classes of populations, three environmental conditions and two breeding methods, both conducted for 10 cycles. The traits were characterized by different degrees of dominance. The values 2 and -2, 1 and -1, 0.5 and -0.5, and 0 were used to define overdominance, complete dominance, partial dominance and no dominance, respectively. A positive value indicated dominance of a favorable gene (one that increased trait expression) whereas a negative value indicated dominance of the unfavorable gene (one that decreased trait expression). Each trait was assumed to be determined by 10 genes with an assortative distribution. Additional assumptions included absence of epistasis, Hardy-Weinberg equilibrium and linkage equilibrium.Since the frequencies of favorable genes in a population can range from 0 to 1, we attempted to represent all possible populations by using three categories, namely, an unimproved population, a population with intermediate frequencies of favorable genes and an improved population. The frequencies of the favorable genes for these classes were assumed to be 0.1, 0.5 and 0.9, respectively. The experimental conditions or degree of error control also varied, which resulted in changes in the parametric values for heritability based on the magnitude of the environmental effects that were introduced. This approach accounted for situations of high (90%), intermediate (50%) and low (10%) heritability. Because of the difficulty in precisely establishing the desired heritability value, a variation of ±4% in the desired value was allowed. The breeding methods used were mass selection in one sex and half-sib selection with recombination of selected progenies. In the case of mass selection, the population size was 1000. With half-sib selection, the simulation assumed 200 progenies , with a completely randomized block design, two replications and 25 individuals per plot. The best 10% were selected based on phenotypic values of the individuals and the average phenotypic values of the families. For the recombination plot, the simulation assumed 100 individuals in each selected progeny and an infinite male gamete pool.The genetic gain due to mass selection was calculated as the difference between the parametric mean of the improved population (cycle n + 1) and the mean of the previous population (cycle n). The genetic gain due to family selection was calculated as the difference between the mean of the improved population obtained with family selection and the mean of the previous population, whereas the gain for the selection of superior individuals in the best progenies was calculated as the difference between the mean of the improved population obtained by among and within selection and the mean of the improved population obtained with family selection. A generation of random mating was assumed to occur after each selection cycle. The predicted gains were calculated based on the parametric values of additive and genotypic variances and of narrow and broad sense heritabilities, as well as the estimated values of these parameters. With mass selection, there was no defined constant bias in the estimate of the additive variance. The estimates were also obtained by simulating parent-offspring and mid-parent-offspring regressions (average of 10 estimates for each regression). In the case of half-sib selection, the estimates of additive variance came from analyses of variance. The function of the predicted gain due to within family selection wasor® software (Microsoft Inc.). The sequence of events used was: (1) specification of the trait and effects of the favorable genes, with insertion of the degree of dominance (the same for each gene), (2) characterization of the population, with insertion of the frequencies of the favorable genes, (3) specification of the environmental conditions, with definition of the desired heritability, (4) calculation of the population parametric mean (cycle 0), (5) simulation of the individual genotypes in the case of mass selection, or of the parent genotypes  and 150 individual genotypes for each progeny in the case of half-sib selection, (6) simulation of the genotypic values, environmental effects and phenotypic values of the individuals, (7) in the case of half-sib selection, analysis of variance of the plot phenotypic values , (8) estimation of genetic parameters  and prediction of gains, (9) identification of superior individuals in the case of mass selection, or of the best families in the case of half-sib selection, (10) computation of the gene frequencies in the improved population, and (11) computation of the improved population mean and of realized gains (first cycle). For the other cycles, the same order of events was used, except for events (1) and (3). Note the correspondence between events (10) and (11) for cycle n and events (2) and (4) for cycle n + 1.The simulated data were obtained by using many of the built-in functions of Microsoft ExcelEach combination of trait (7), population (3), heritability (3), breeding method (2) and cycles (10) was repeated ten times and corresponded to 12.600 simulations. In the case of mass selection, when the predicted gain was calculated with estimates of the parameters (biased estimates) only one replication was done .i.e., the level of breeding in the population and the degree of dominance of the genes controlling the traits being studied. As shown here, the prediction of gain from selection is biased, even when the true values of the genetic parameters (unbiased estimates) are used in the calculation. Ignoring biases > 300% that essentially reflected only a small predicted gain and no actual gain, the mean biases in this simulation ranged from 39.2% to 59.3%, depending on the prediction function used. Extreme values generally represented < 10% of the cases and occurred mainly in bred populations with average heritability.Few experimental studies have compared predicted and realized gains, especially using mass selection. This lack of data makes it difficult to compare the results for biases in gain predictions with mass selection . AnotherOverestimation of gain was not a general rule in our analysis. When additive variance or narrow sense heritability was used there was a tendency to underestimate the gain, particularly with low heritability . HoweverThe results of different traits showed that the magnitude of the bias was proportional to the degree of dominance, regardless of whether the favorable genes were dominant or recessive . With prAlthough the Eberhart function yielded biased estimates of genetic gain, our simulation indicated that this function was adequate for assessing the efficiency of recurrent population breeding methods and selection strategies. The correlation between realized and predicted genetic gains during 10 cycles was generally positive and of high magnitude (average of 0.84) . The excWhen gain is predicted based on biased estimates of the genetic parameters, the additional bias can increase or decrease the difference between the realized and predicted gains. Using estimates of additive variance (obtained by parent/offspring and mid-parent/offspring regressions) and genotypic variance , the simulation study confirmed almost all of the previous inferences. The exception was a small bias in a bred population, for which the mean magnitude ranged from 27.4% to 47.9%, depending on the prediction function. The bias in the estimates of additive variance ranged from -30.1% to 24.6%, with a predominance of underestimation (71.4% of the cases), which explained the smaller magnitude of the bias observed here. With few exceptions, the realized and predicted gains during 10 cycles were also in full agreement (average correlation of 0.80).The results of bias in predictions of gain from family selection showed similarities and differences compared to those obtained with mass selection . AlthougThe mean absolute values of biases by trait, population and heritability were larger with complete dominance and overdominance (21.4%), in bred populations (28.9%) and with low heritability (23.8%) . The meaThe gain prediction from family selection was a poorer indicator of the efficiency of recurrent population breeding methods and selection strategies compared to similar prediction from mass selection . The lini.e., -18.4% with progeny selection and -78.4% with selection of individuals in the selected families. As expected, bias in gain prediction from within selection was much larger than bias in gain prediction from among family selection.Comparison of the predicted and realized gains based on the selection of individuals in the best families yielded poor results Tables  and 4. IGreater biases were observed for traits controlled by favorable dominant genes  and traits not controlled by allelic interaction effects (average magnitude of 143.8%) . The aveAn additional negative aspect of gain prediction from individual selection within the selected families was shown by the correlation between predicted and realized gain during 10 cycles. Regardless of the magnitude of the bias in additive variance, the correlation was negative in ~40% of the situations assessed  but was i.e., broad versus narrow sense heritability, increased the magnitude of bias without worsening the correlation between predicted and realized gains. These findings indicate that Eberharts formula, which is a function of additive variance or narrow sense heritability, is a less biased estimator of genetic gain than the estimator based on a function of genotypic variance or broad sense heritability. As shown for mass and family selection, there was full correspondence between the gains calculated with additive or genotypic variance and the predictions based on broad or narrow sense heritability.In conclusion, the use of unbiased and biased estimates of the genotypic variance within progeny rather than the within family additive variance,


Objective: To examine the efficacy of a new topical capsaicin presentation as an oral rinse in improving the symptomsof burning mouth syndrome (BMS).Study design: A prospective, double-blind, cross-over study was made of 30 patients with BMS. There were 7 dropouts; the final study series thus comprised 23 individuals. The patients were randomized to two groups: (A) capsaicin rinse (0.02%) or (B) placebo rinse, administered during one week. After a one-week washout period, the patients were then assigned to the opposite group. Burning discomfort was scored using a visual analog scale (VAS): in the morning before starting the treatment, in the afternoon on the first day of treatment, and at the end of the week of treatment in the morning and in the afternoon. The same scoring sequence was again applied one week later with the opposite rinse.Results: The mean patient age was 72.65 ± 12.10 years, and the duration of BMS was 5.43 ± 3.23 years on average. Significant differences in VAS score were recorded in the capsaicin group between baseline in the morning (AM1) or afternoon (AA1) and the end of the week of treatment (AA7).Conclusion: The topical application of capsaicin may be useful in treating the discomfort of BMS, but has some limitations. Key words: Burning mouth syndrome, stomatodynia, capsaicin, treatment, clinical management. Burning mouth syndrome (BMS) manifests as a burning sensation of the tongue, lips or entire oral cavity, in the absence of any objective lesions or laboratory test findings capable of accounting for the discomfort . PatientThe diagnosis of the syndrome is based on the clinical manifestations. The underlying cause is unknown, though many potentially influencing conditions have been cited, such as local, general and psychopathological factors. More recently, BMS has been associated to a neuropathic mechanism affecting peripheral or central levels of the nervous system -6.Very few cases of spontaneous remission of the symptoms have been reported. The treatments proposed for controlling the discomfort caused by BMS include alpha-lipoic acid, cognitive-behavioral therapy, the administration of anticonvulsivants (particularly clonazepam), and topical capsaicin ,7,8. HowTopical capsaicin has been used as a treatment alternative for controlling neuropathic pain. This substances induces desensitization to thermal, chemical and mechanical stimuli. It has also been used for the treatment of the discomfort caused by BMS, with positive results. Petruzzi et al.  showed 0The present study was designed to examine the efficacy of a new topical capsaicin presentation as an oral rinse in improving the symptoms of BMS. In addition, the possible adverse effects of such treatment were evaluated. -Study designA prospective, double-blind, cross-over study was made involving randomized patient distribution to treatment. BMS was diagnosed according to the current criteria, and the discomfort had been present on a daily basis for at least 6 months . A visuaThe patients were randomized to two groups: (A) 0.02% capsaicin rinse or (B) placebo, administered three times a day. The rinses were applied for about 30 seconds in volumes of 15 ml. A baseline assessment of discomfort was made in the morning before treatment in both the capsaicin group (AM1) and in the placebo group (BM1). The VAS score was then again recorded in the afternoon of the first day of treatment in both groups (AA1 and BA1) and at the end of one week of treatment in both groups, in the morning (AM7 and BM7) and in the afternoon (AA7 and BA7). After this first week of treatment, the patients completed a one-week washout period , after which they were assigned to the opposite group for a further week of treatment. During this cross-over period, treatment and the scoring of discomfort were carried out in the same way as in the first week, but administering the opposite oral rinse. Thus, all of the patients used both rinses (capsaicin and placebo) and were scored for discomfort at the start of the study, after one week, and again after three weeks. The patients were also questioned about possible adverse effects or discomfort caused by the treatments.  -Patient selectionSince this was a pilot study and the number of publications on topical capsaicin for treating BMS is limited, we analyzed 23 patients  out of a total of 30 initially planned subjects (7 dropped out in the first week of the study). The patients were randomized at the start of the first week (12 in one group and 11 in the other).The study included patients diagnosed with BMS and with a minimum duration of the disease of 6 months. The enrolled subjects were required to use no specific medication or treatment capable of interfering with BMS, for at least one month prior to the start of the study, and written informed was obtained in all cases. On the other hand, patients with contraindications to topical capsaicin treatment were excluded from the study, as were those with serious systemic disease at the time of patient screening, patients with oral mucosal lesions that might explain the burning sensation, and subjects unable to correctly score discomfort on the VAS scale. Lastly, where indicated, those subjects who developed adverse effects were removed from the study.The study was approved by the Clinical Research Ethics Committee of Dr. Peset University Hospital . -Data analysisThe SPSS version 15.0 statistical package for Microsoft Windows was used to analyze the data. Qualitative variables were represented by their absolute (n) and relative (%) frequencies, while quantitative variables were reported as the median and range. The effects of the capsaicin rinse and placebo formulation were evaluated, comparing the distribution of the VAS scores for each rinse at the different study timepoints , based on the Wilcoxon test. Statistical significance was considered for p < 0.05.The study initially involved 30 patients, of which 7 (23.3%) abandoned the trial in the first week of treatment. Of these 7 individuals, four belonged to the capsaicin group . In turn, in the control group three patients abandoned the study during the first week because of a lack of therapeutic effect.Thus, the study finally comprised 23 patients with BMS yielding cross-over measurements of discomfort (23 in group A and 23 in group B).The mean patient age was 72.65 ± 12.10 years (range 40-90 years). Most of the patients (65.2%) were between 70 and 80 years of age. The mean duration of the disease was 5.43 ± 3.23 years (range 1-14 years). Patients with a BMS duration of 4 and 5 years represented 39.1% of the total (n = 9).On examining the VAS scores at the start and end of the first week in both groups (A and B), based on the Wilcoxon test, differences were found between 0.02% capsaicin in the morning AM1) and afternoon of the first day (AA1) and end of the week (AA7) after application of the capsaicin rinse.Burning sensation affecting the tongue, lips or entire oral cavity may be a symptom of some underlying disorder affecting the oral mucosa, or may be the principal manifestation of a form of idiopathic stomatodynia known as burning mouth syndrome (BMS) . The latIn our study capsaicin was evaluated in oral rinse formulation, which showed a degree of efficacy in improving the symptoms of BMS over short periods of time. In effect, the visual analog scale (VAS) used to score discomfort revealed significant improvement of at least two points on average after 7 days of treatment with capsaicin rinse versus baseline. No such improvement was observed with the placebo formulation. The patients were recruited on the basis of strict and homogeneous diagnostic criteria. In this sense, many of the studies published to date lack such strict criteria, and the sample characteristics moreover vary from one study to another .Petruzzi et al.  also obsHowever, it should be noted that there are clear limitations to the use of topical capsaicin, such as limited effect over time and a limited magnitude of improvement . While tMoreover, the burning sensation produced on using the capsaicin rinse limits its use – though the discomfort threshold varies among patients ,14.Topical capsaicin has been used as a treatment alternative for controlling neuropathic pain in general. The drug is normally used at concentrations of between 0.025% and 0.075%, inducing desensitization to thermal, chemical and mechanical stimuli when applied topically .The mechanism of action involves interaction of capsaicin with the vanilloid receptor (VR1) of the C type sensory nerve fibers . These r


Locating the pyramidal tract (PT) is difficult in patients with thalamic or basal ganglia tumors, especially when the surrounding anatomical structures cannot be identified using computed tomography or magnetic resonance images. Hence, we objected to find a way to predict the location of the PT in patients with thalamic and basal ganglia tumorsIn 59 patents with thalamic or basal ganglia tumors, the PTs were constructed by with diffusion tensor imaging (DTI)-based fiber tracking (FT). In axial slices crossing the foramen of Monro, the tumor position was classified according to three lines. Line 1 was vertical and crossed the vertex point of the anterior limbs of the internal capsule. Lines 2 and line 3 were horizontal and crossed the foramen of Monro and joint of the middle and lateral thirds of the posterior limbs, respectively. Six (10.17%) patients were diagnosed with type 1 tumor, six (10.17%) with type 2, seven (11.86%) with type 3a, five (8.47%) with type 3b, 17 (28.81%) with type 4a, six (10.17%) with type 4b, three (5.08%) with type 5, and nine (15.25%) with type 6. In type 1 tumors, the PTs were located at the 12 o'clock position of the tumor, type 2 at six o'clock, type 3a between nine and 12 o'clock, type 3 between six and nine o'clock, type 4a between 12 and three o'clock, type 4b at three o'clock, type 5 between six and nine o'clock, and type 6 between three and six o'clock.The position of the PT relative to the tumor could be determined according to the tumor location. These results could prove helpful in determining the location of the PT preoperatively. Thalamic and basal ganglia tumors account for approximately 1–5% of cerebral tumors and are frequently encountered in children and young adults MRI scanning was approved by Medical Science Ethics Committee of General Hospital of the Chinese People's Liberation Army. Signed informed consent was provided by each patient or by an appropriate family member before MRI scan.We collected data retrospectively on patients with thalamic or basal ganglia tumors in our hospital from March 2009 to March 2011. All patients received MRI scans, and tractogram of the PT were constructed by DTI-based FT. If the PT was affected severely by the tumor or edema and the PTs could not be revealed by DTI-based FT, the patient was excluded. Patients were also excluded if tumors were found in other regions, such as the frontal, parietal and occipital lobe, because these tumors might demonstrate different and more complicated growth patterns.MRI scans were performed with a 1.5 Tesla scanner . The DTI data were acquired with single-shot spin-echo diffusion-weighted echo-planar sequence . The diffusion-weighting  was 1000 s/mm2. This sequence is based on a balanced diffusion gradient design which strongly minimizes eddy-current artifacts compared to a single-refocused design The diffusion weighted images was processed by the “Fiber Tracking” module of the navigation planning software iPlan 2.6  for fiber tracking, which utilizes a tensor deflection algorithm The location of the PT was investigated at the axial slice crossing the foramen of Monro. In order to avoid confusion and facilitate the description, all the tumors on the right side were mirrored to the left side, so that the relative position between the PT and tumor would not change in these mirrored images . The areA third line was drawn for further classification of type 3 and type 4 tumors. The third line was parallel to the second line and crossed the joint of the middle and lateral thirds of the posterior limb of the internal capsule in the normal hemisphere . Based oIn total, there were 61 patients with thalamic or basal ganglia tumors in our hospital from March 2009 to March 2011. Two patient were excluded because the consistency between FT results of the two operators was below the standard (κ>0.7). In the first patient, the fibers of the whole internal capsule were severely affected by the tumor and surrounding edema. The fibers of the PT can only be traced with FA threshold of 0.1 and nearly all the streamlines depicted by the software interrupted before reaching the precentral gyrus. In addition, the lower FA (0.1) threshold made the streamlines increased dramatically. But without the help of precentral gyrus and clearly surrounding anatomical structures, identifying the streamlines belonging to PT became subjective. This made the consistency between the two operators much lower. In the second patients, the PT was dislocated obviously by the ganglion tumor and made the PT formulate a narrow angle besides the tumor. This made the software couldn't depict the whole course of the PT, leading to low consistency between the two operators. At last, 59 patients  were enrolled for analysis. In these patients, the PT were successfully constructed with good consistency between two operators.In the 59 patients harboring tumors in the basal ganglion or thalamic region, six (10.17%) patients presented with type 1 tumors, six (10.17%) with type 2, seven (11.86%) with type 3a, five (8.47%) with type 3b, 17 (28.81%) with type 4a, six (10.17%) with type 4b, three (5.08%) with type 5, and nine (15.25%) with type 6.The PTs were constructed successfully in all 59 patients. In the six patients with type 1 tumors, all PTs were located at the 12 o'clock position. However, in the six patients with type 2 tumors, the PTs were located at the six o'clock position. Tumors in 12 patients were classified as type 3. The PTs of these patients all were situated on the medial side of the tumors. Specifically, in the seven patients with type 3a tumors, the PTs were between nine and 12 o'clock. In contrast, in the five patients harboring type 3b tumors, the PTs all were located between six and nine o'clock. There were 23 patients harboring type 4 tumors. In these patients, the PTs were situated on the lateral side of tumor, between 12 and three o'clock in 17 patients with type 4a tumors and at three o'clock in five patients with type 4b tumors. In the three patients with type 5 tumors, the PTs were located between six and nine o'clock. In the nine patients with type 6 tumors, the PTs were between three and six o'clock. The majority of body of the tumor laid on the lateral side of line 1 in 15 (25.42%) patients (type 3 and type 5). In these 15 patients, the position of the PTs surrounded the medial half of the tumor. On the contrary, the PTs surrounded the lateral half of the tumor when the majority of the tumor body lay on the medial side of line 1 in another 32 (54.23%) patients (type 4 and type 6). The main body of the tumors were above line 2 in 18 (30.5%) patients , and the PTs all were below the tumor's lowest point. Except for patients with type 1, the tumors were mainly located below line 3 in 24 (40.68%) patients (type 3a and type 4a) and the PTs were distributed around the upper half of the tumor in these patients. The majority of the tumor body was situated between line 2 and line 3 in 11 patients (type 3b and type 4b) and the PTs of these patients surrounded the lower half of the tumor. In the six patients with type 1 tumors, four were mainly below line 3, while another two were situated above this line. Hence, the rule regarding line 3 did not consistently apply to type 1 tumors.The position of the PTs is one of the most important pieces of information for formulating a surgical strategy for thalamic or basal ganglia tumors By using DTI-based FT, we successfully constructed all the PTs in this group of patients. The accuracy of this technique is still controversial in the literature By analyzing the results of DTI-based FT, we found that three lines could help in determining the position of the PT relative to the thalamic or basal ganglia tumors, even when the tumors were large and the anatomical landmarks could not be determined. Line 1 was vertical and crossed the vertex point of the anterior limbs. Based on this line, we confirmed that the PT was on the lateral or medial side of the tumor. Line 2 and line 3 were horizontal and crossed the foramen of Monro or the joint of the middle and lateral thirds of the posterior limbs. These two lines could help in determining whether the PT followed the upper half or lower half of the tumor. As a result, tumors could be classified into eight types based on these three lines. Additionally, we further confirmed that PT position in every type of tumor had a relatively fixed pattern that appeared to be consistent. The possible reasons for this phenomenon were the PT location in the posterior limbs and special anatomical features of basal ganglion.Historically, it was believed that the PT was located at the anterior portion of the posterior limb of the internal capsule with thalamic or basal ganglia tumors. The opinion that the PT was located at the posterior portion of the posterior limb of the internal capsule, however, seems to prevail in current research studies In the two patients with thalamic or basal ganglia tumors, the fiber tracking results of the PT had low consistency between the two operators. One was because the PT was severely affected by the tumor and surrounding edema. The difference of fiber tracking result of the two operators in this patient lied in the boundary of the PT. But their positions relative to tumor were consistent. The other was because the PT was dislocated obviously and formulated a narrow angle. In this patient, the positions of tracking result between the two operators were different in the axial slice crossing the foramen of Monro. The gap was about 4 mm. Even so, the relative positions between the two tracking results and tumor were consistent. These two cases still demonstrated the intrinsic characters of the algorithm of tensor calculation and fiber tracking. But, the course of the fiber tracts accurately, especially for the densely packed PT fibers, should be accurate Tumors in the thalamus and basal ganglion can be classified into eight types according to surrounding anatomical landmarks. The PT location in each type of tumor was characteristic and consistent. These results may aid surgeons in determining PT location preoperatively.


The objective of this prospective study conducted in November 2008, was to determine the prevalence and the factors associated with Hepatitis C Virus (HCV) infection in chronic hemodialysis patients.The study was carried out in the hemodialysis unit of the university teaching hospital of Point G. Serum samples were tested for anti-HCV antibody, anti-HIV antibody and HBs Ag using enzyme immunoassay methods (ELISA) at the laboratory of immunology of the National Blood Transfusion Service of Bamako. The following parameters were assessed: initial nephropathy, duration of the dialysis, history of blood transfusion, number of blood units transfused since the beginning of the dialysis, history of nosocomial exposure.A total of 66 patients were enrolled. The mean age of the patients was 42,27±14, 8 years, with a male to female sex-ratio of 1,44. Anti-HCV antibodies were found in 13 chronic hemodialysis patients, leading to a prevalence of 19,7%. A significant association was found between the bearing of HCV and the duration of the dialysis.These results indicate that hepatitis C is frequent in the chronic hemodialysis patients of the university teaching hospital of Point G, and that the duration of dialysis constitutes the main factor associated with the contamination by the HCV.None declared


The electrical signals measuring method is recommended to examine the relationship between neuronal activities and measure with the event related potentials (ERPs) during an auditory and a visual oddball paradigm between schizophrenic patients and normal subjects. The aim of this study is to discriminate the activation changes of different stimulations evoked by auditory and visual ERPs between schizophrenic patients and normal subjects.Forty-three schizophrenic patients were selected as experimental group patients, and 40 healthy subjects with no medical history of any kind of psychiatric diseases, neurological diseases, or drug abuse, were recruited as a control group. Auditory and visual ERPs were studied with an oddball paradigm. All the data were analyzed by SPSS statistical software version 10.0.In the comparative study of auditory and visual ERPs between the schizophrenic and healthy patients, P300 amplitude at Fz, Cz, and Pz and N100, N200, and P200 latencies at Fz, Cz, and Pz were shown significantly different. The cognitive processing reflected by the auditory and the visual P300 latency to rare target stimuli was probably an indicator of the cognitive function in schizophrenic patients.This study shows the methodology of application of auditory and visual oddball paradigm identifies task-relevant sources of activity and allows separation of regions that have different response properties. Our study indicates that there may be slowness of automatic cognitive processing and controlled cognitive processing of visual ERPs compared to auditory ERPs in schizophrenic patients. The activation changes of visual evoked potentials are more regionally specific than auditory evoked potentials. The cognitive slowing or delay whether occurs in schizophrenic patients or not, has been debated for long time . The stuThe aim of this study is to investigate the difference of auditory and visual long-term evoked potentials between schizophrenic patients and normal subjects. We have applied the Biologic System Company's Evoked Potential System (EP) microcomputer-based system to collect and analyze human electroencephalogram (EEG) signals. The data contains of the patient's EEG responses to two different auditory and visual stimuli using the oddball paradigm. Electrical signals measured at standard locations on the scalp were processed to detect and identify the visual and auditory ERPs in schizophrenic patients.Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria . The ERPs were elicited by tone pips of 50-ms duration  using the stimulation rate of 1.3/s. The infrequent (16.7%) high-pitched tones  were presented randomly interspersed with frequent low-pitched tones  binaurally. The amplifier was used by the specifications, high filter, 30; low filter; 1.0; and gain, 20,000. The time of analysis was 512 ms and the sensitivity was 122.5 mV in auditory EP testing. Subjects were asked to count the presence of infrequent high-pitched tones and ignore the frequent low-pitched tones by mental process. The error index was used to display the accuracy of the count. The artifact of vertical eyeball movement was detected from electrodes placed above and below the right eye and horizontally from electrodes placed at the left outer canthus. The data was discarded if there were more than 5 artifacts and the subjects were retested after 5 minutes.The subjects were seated comfortably in a dimly lit chamber with a portable eye-trek device  that was approximately 2 cm in front of their eyes. The visual oddball paradigm has a full-field, 1 × 1, square, black and white flashes, stimuli rate of1.3/s, bandpass of 30 and 1 Hz. The analysis time of 512 ms and sensitivity of 122.5 mV were used in visual EP testing. The latencies and the amplitudes of N100, N200, P100, P200, P300, and P400 waves were determined ,20. All The total averages were computed for the brain responses to target tones. The Peak P300 amplitude, which accounts for individual variations in P300 latency, was measured as the most positive point from 250 to 400. The Peak P400 amplitude, which accounts for individual variations in P400 latency, was measured as the most positive point from 400 to 500. The components of ERPs were identified and are shown in Figure P values were reported as two-tailed. P < 0.05 was accepted as statistically significant. All the data were analyzed by SPSS statistical software.A one-way analysis of variance (ANOVA) has been used to compare the ERPs  between the schizophrenic patients and the healthy subjects. To avoid the type I error, all the The average waveforms of these two groups were displayed for midline electrode sites  in amplitude and latency Table  &2. The p < 0.01) for 43 schizophrenic patients and 40 control subjects after the subject-mean ERP was subtracted from each trial. The average ERP of an auditory and the visual stimulus and the peaks conventionally termed N100, P200, N200 and P300. There are more differences in amplitude and latency of ERP over N100, P200, N200 and P300 between control and schizophrenic groups after auditory oddball paradigm. Only the latency of ERP over P300, amplitude of ERP over N100, latency and amplitude of ERP over N100 and amplitude of ERP over N200 are different between the control and the schizophrenic groups after visual oddball paradigm. The scalp map indicates that the visual ERP is more specific to identify the schizophrenic patients than the auditory ERP over the Fz, Cz and Pz regions.The differences in latencies and amplitudes submitted to the ANOVA between the patient and the control groups are illustrated in Tables t test is performed to compare signal processing models, assuming a unique and common mechanism as the locus of action of this effect. It includes visual or auditory ERPs with or without counting process. ERPs recorded in this process, serially presented tones or flashes, which could be in either the auditory or visual modality.Clinically, the delay of the P300 latency is a nonspecific change in psychiatric disorder. It can also be found in dementia, schizophrenia, depression, and other organic mental disorders ,22-24. TAccording to the detailed demographic data, there were no differences in sex, age, marital status, or religion, but there were significant differences in educational qualification. In the control group, there were no differences in the latency component of visual ERPs with or without counting, but the early N100  and delayed P200 (Pz) in auditory ERPs with counting were noted. In the schizophrenic patients, there were no differences in the latency component of visual ERPs with or without counting except delayed P400  in visual ERPs with counting. However, early N200  in the auditory ERPs with counting was also noted observed. This finding shows that in either counting or without counting process the latency of visual ERPs This finding shows that in either counting or without counting process the latency of visual ERPs waswas unchangeable and unique in healthy subjects thus. This means that the latency of auditory ERPs was much more influenced by attention than visual ERPs. Otherwise, the decreased N200 , decreased P200 , increased P300 , and increased P400 (Pz) amplitude components of visual ERPs with counting but decreased P200  in auditory ERPs with counting were noted in the control group. It is also observed that, in the case group, there were no differences in the amplitude components of visual ERPs with or without counting, but increased P200  and P300  in auditory stimuli the ERPs with counting were noted. This finding shows that the amplitude of visual ERPs was changed in the mental process with counting in healthy subjects but not in schizophrenic patients. This could be the result of a deficiency of signal processing in visual ERPs among schizophrenic patients. In the amplitude of auditory ERPs with counting, the P200 and P300 amplitudes increased in schizophrenic patients, proving that the signal processing enhanced by counting was observed in schizophrenic patients. In other words, the schizophrenic patients could lack abilities, such as attention, required for signal processing.However, the P400 component exists in visual ERPs. The P400 component was identified as a positive wave at Fz, Cz, and Pz, with a latency of 300 to 500 ms after the start of the stimulus. There were no differences in the latency components in the control group with or without counting process, but there was an increased P400 (Pz) amplitude component in the control group with the counting process. There was also a significant prolonged latency of P400  in the patient group with the visual counting process. The delayed latency of P400 in the visual counting process was observed in schizophrenic patients, which can be used for differential diagnosis clinically.t test analysis of case and control groups, the latency components of P300  in visual ERPs without counting or N200  and P300  in auditory ERPs with or without counting were significantly different between the case and control groups. This finding indicates that delayed latency of N200 and P300 in the auditory ERPs and P300 in the visual ERPs can be clinically correlated to schizophrenic patients. However, the amplitude components of N100  and N200  in visual ERPs with counting; N100  in visual ERPs without counting; N100 , N200 , P200 (Fz), and P300  in auditory ERPs with counting; or N100 , N200 (Cz), P200 (Fz), and P300  in auditory ERPs without counting were significantly different between case and control groups. This finding implies that decreased amplitude of N100, N200 and P300 in the auditory ERPs and N100 in the visual ERPs can indicate clinical correlation among schizophrenic patients.In the paired Student Various studies have shown that the amplitude of the P300 component of ERP is reduced in schizophrenic patients . It is aAccording to our study no matter what the auditory stimuli  are, the amplitude components of N100, N200, P200, and P300 and the latency components of N200 and P300 were significantly different between the control and the schizophrenic patients. However, the amplitude of N200  induced by the visual stimuli with mental counting was significantly different between the control and the schizophrenic groups. The latency of P300 was not different between the two groups, which mean that some mental processing occurs at the N200 level during visual stimuli but that schizophrenic patients lack this ability. However, when the schizophrenic patients tried to use mental counting in the visual stimuli, the P300 latency was not different between the two groups. This indicates that the time of mental processing is not delayed among schizophrenic patients.Because of their millisecond-level temporal resolution, ERPs are ideally suited for analysis of the brain activity related to information processing. A major finding of the present study is that the amplitude of N200 and P300 used as an index of cortical processing is delayed in schizophrenia. Mismatched negativity reflects activation of neural structures within primary auditory cortex (Heschl's gyrus) or adjacent supra-temporal auditory regions, as opposed to N200, which primarily reflects activity within auditory association cortex, and P3, which reflects activity in prefrontal, temporo-parietal, and, potentially, other multiple sensory association regions of the cortex. Our findings, therefore, indicate that the neuro-physiological dysfunction in schizophrenia is prevalent and extends even to the level of the sensory cortex .An important aspect and contribution of this study is to integrate the auditory and the visual ERPs for patients with schizophrenia. The implementation of such tools may be significantly used for clinical interventions. People with schizophrenia may be followed up with such tools in the longitudinal follow-up study. Since there is no evidence of any published literature along with all meta-analyses, a caution should be taken into account while interpreting the results. Patients with schizophrenia should be considered separately for the study from those with different types if large sample size.This study demonstrated on visual ERPs indicates that there may be a slowness of automatic cognitive processing and a controlled cognitive processing in schizophrenia. The P300 latency implies that the controlled cognitive processing in schizophrenia is influenced by slower information input at mismatched negativity, which reflects activation of neural structures within primary auditory cortex (Heschl's gyrus) or adjacent supra-temporal auditory regions. The auditory and visual P300 latency can be a very powerful evaluation tool to study the condition of schizophrenia, although the auditory N100 and the visual N100 amplitude and latency may contribute to ERP results when the patients and the normal control subjects are compared. These findings can be used for future applications of N100 and P300 in the study of this particular disorder by enhancing measurement sensitivity and promoting greater clinical utility.However, N200 primarily reflects activity within the auditory association cortex and P3 reflects activity in prefrontal, temporo-parietal and potentially other multiple sensory association regions of the cortex. This study shows how the application for auditory and visual oddball paradigm identifies task-relevant sources of activity and allows separation of regions that have characteristic response properties. The activation changes of visually evoked potentials and are more specific regionally than auditory evoked potentials are. In the clinical implications, the implementation of such tools may be significantly useful for clinical interventions. It is therefore possible to integrate the auditory and the visual ERPs for patients with schizophrenia. People with schizophrenia may be followed up by such tools in the longitudinal study in future.The authors declare that they have no competing interests.KSC and MWH conceived the study, designed the protocol, analyzed the data and prepared the manuscript. PYL participated in the study design and significant comments on the manuscript. FHC participated in the study design and helped to draft the manuscript. All authors have read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/11/74/prepub


The assessment of health-related quality of life (HRQL) in the perception of patients with chronic diseases such as juvenile idiopathic arthritis (JIA), reflects the effectiveness of the interventions to which those patients have been submitted.To assess the HRQL of the JIA patients participating in a standard physiotherapy program, according to the arthritis subtype.post hoc the Duunn test has been used in order to compare the median and percentiles (25 and 75) of the scores of these instruments in the baseline and end-of-6-months periods.Clinical trial of a consecutive sample of 26 JIA (ILAR) patients of the Oligoarticular , Polyarticular  and Systemic % subtypes, with an average 11,2±4,1 years of age. The patients participated in a standard physiotherapy program twice a week for 6 months. The Chi-square test has been used in order to evaluate the attendance to the program. The HRQL has been assessed by means of the PedsQL 4.0 and the Kruskal-Wallis test with The attendance of the patients to the submitted program has been significant  with an average of 45±1,1 of the 48 sessions proposed to each patient. A significant difference has been detected  between the median and percentiles (25 and 75) of the oligoarticular subtype in the in the psychosocial summary of 46,7  versus 70,7 and in the overall score of the PedsQL 4.0 of 49,1  versus 72,2  in the baseline and end-of-6-months periods.The standard physiotherapy program has promoted a positive impact in the HRQL of JIA patients of the Oligoarticlar subtype. The psychosocial aspects have been responsible for this impact. Randomized, controlled studies with a larger patient sample are necessary for the inference of these results. The perception of the patients in relation to the therapeutic measures they are submitted to is essential for the success of the treatment.