Studies showed an influence of the type of mutation (genotype) on the various expressions (phenotypes) of the MH susceptibility. The aims of this study are to look for any correlation between the presence of a MH mutation and 1) the severity of the anesthetic complication and 2) the force of the contractures observed in the IVCT.Malignant hyperthermia (MH) is a complication of anaesthesia appearing as an acute potentially lethal hypermetabolic state in people carrying a genetic anomaly expressed in the skeletal muscle. MH susceptibility can be diagnosed by Observational analytical retrospective anonymized study based on the informations contained in the Lille MH Database. The criteria of inclusion were: 1) anesthetic probands classified as MHS according to the IVCT and/or the presence of a MH mutation in the RYR1 gene in at least one family member and 2) existence of sufficient clinical information concerning the crisis. The severity of the MH crisis was classified as: death, survival after stay in intensive care unit ICU, survival without stay in ICU. The results of the IVCT: maximal force of contracture at halothane 2%, caffeine 2mmol/L, halothane 3%. The statistical analysis was carried out with a test of Chi-2 for the comparisons of frequency and a test of Mann Whitney for the nonparametric variables with p<0,05 significant.92 MHS probands were included in the study: 63 men (68%) and 29 women (32%) over a period going from 1964 to 2013. The age at the moment of the crisis is 18,9 years . Mutations were found in 59 families (64%) including 53 causal mutations (58%) and 6 probable (6%). No significant difference was observed in the degree of severity between the 2 populations. The force of contracture of the IVCT was significantly higher in the group with MH (Table In this study, the severity of the MH crisis is not related to the presence of MH mutations. It is well known that the severity is more dependent on environmental factors, age of the crisis, exposure time to the volatile anesthetic agents, administration of dantrolene. On the other hand, the presence of a MH mutation in gene RYR1 modifies the muscular phenotype since the force of contracture in the IVCT is significantly more important in this group. These results support the genetic heterogeneity of the disease.


Atopic dermatitis (AD) is known as having an important influence in the quality of life (Quol) of patients and their families, even though, the impact of the subcutaneous specific-allergen immunotherapy (SCIT) in this field has sparsely been accessed. This project aims to evaluate the effect of SCIT in the Quol of Brazilian patients with moderate/severe AD and their families.Dermatophagoides pteronyssinus and/or Blomia tropicalis) and clinical relevance of these allergens. To access the quality of life of patients and their families, we used specific questionnaires previously validated to Brazilian Portuguese, the Infant’s Dermatitis Quality of Life Index (IDQoL) and Dermatitis Family Impact Questionnaire (DFI), and applied before and after 12 months of the use of SCIT. The Quol index scores were evaluated from 0 (best index of Quol) to 32 (worse index of Quol).We analyzed 40 patients with diagnosis of moderate/severe AD based on the SCORAD and allergological work-up, under follow-up in the Allergy Department of our Hospital between 2012 to 2014. The cluster SCIT has been indicated based on the dust mite specific-IgE . Meanwhile, the average DFI was 13.54 in the first evaluation and 8.5 in the last evaluation (P<0.001). A positive correlation was observed between the severity of AD and IDQoL scores. The most important factors related to the decrease of the IDQoL were the improvement of pruritus (from 2.4 index to 0.9), quality of sleep (from 1.6 to 0.9) and feelings for having a cutaneous disease (from 1.3 to 0.7), the only domain we didn’t find significant difference was related to the impressions the patients have regarding the ongoing treatment . The major important domains of the DFI scores differences were the quality of the family’s sleep (from 1.0 index to 0.3), leisure (from 1.0 to 0.5) and costs (from 1.8 to 1.3). No significant difference was seen in the domain regarding the responsibility of the family on keeping the patient’s treatment.This study demonstrates that AD severity impaired the IDQoL as well as the DFI. The SCIT showed to be effective on increasing the Qol of AD patients and in their families, decreasing the index of the majority of both IDQol and IDF domains.


In this work we present a stoichiometric reaction mechanism for the photocatalytic ethanol oxidation on TiO2(110). 2(110). The reaction products are analyzed either under reaction conditions or after irradiation at lower temperatures. Water is identified as a quantitative by-product, which resides in a defect site. These water molecules cause a blocking of the defect sites which results in poisoning of the catalyst. By different preparation techniques of the TiO2(110) surface, the role of surface defects is further elucidated and the role of molecular oxygen is investigated. Based on the investigation, a complete photochemical reaction mechanism is given, which provides insights into general photon driven oxidation mechanisms on TiO2.In this work we present a stoichiometric reaction mechanism for the photocatalytic ethanol oxidation on TiO Since the discovery of its photocatalytic activity, TiO2 has become the most explored heterogeneous photocatalyst to date.5 While photocatalytic mechanisms of simple model reactions  on the surface are well understood,9 the photochemical mechanisms of small organic molecules on bare TiO2(110) remain unclear. For almost any reaction not even all reaction products have so far been identified.17 The understanding of the exact photocatalytic processes for such reactions will, however, be highly beneficial, since a fundamental understanding will allow for improvement of titania-based photocatalysts, in general. This is also the reason why the photochemistry of such systems has attracted considerable attention within the last few years.19 In this regard, ethanol is in particular of significant interest, because this molecule serves as a precursor for biomass fuels, due to its C–C-bond.20 Furthermore, its functional group makes ethanol a potential precursor for the green photocatalytic hydrogen production, especially since alcohols can be obtained as a renewable feedstock from biomass.23 Therefore, the elucidation of the ethanol chemistry on TiO2 represents an important step towards the understanding of the H2-production from renewable sources with light on metal-semiconductor hybrid materials.The thermodynamically stable rutile TiO2(110) surface.16 Idriss and coworkers observed the photoreaction of ethanol to acetaldehyde with a strong dependency on the oxygen pressure on an oxygen covered surface. In a more recent study, however, Yang and co-workers have reported a photo-oxidation of ethanol under exclusion of oxygen, focussing on its photocatalyzed dissociation.24 For adsorbed propanol, analogous production of propanal was observed and a similar dependence on the O2 concentration was found as well.25 The group of Henderson reported the oxidation of methanol to formaldehyde on a defect-rich crystal surface in the absence of any O2 and determined the surface-bound methoxy as the active reactant.26 Consecutive photocatalyzed coupling reactions have also been reported in the literature.28Considering the reaction pathway, it is known that alcohols generally undergo a hole-mediated oxidation process on a rutile TiO2 are presented. The mechanisms unravel the role of oxygen and surface defects and are supported by studies based on different preparation conditions for the titania crystal and on the analysis of water as one of the main products of the photoreaction.All studies up to date have only investigated the main photo-product and postulated mechanisms based on plausible assumptions. Thus, the stoichiometric reaction equations have been made without the analysis of any by-products and unknown charge states. For the total reaction pathway, the role of defects in the reaction still remains unclear, especially when oxygen is added as a reactant. In this work stoichiometric mechanisms for the photochemistry of ethanol on rutile TiO–11 mbar. Briefly, it consists of a liquid-N2 cooled, x, y, z, φ-manipulator (VAB Vakuum GmbH), an Auger Spectrometer , a sputter gun , a QMS , leak valves (Pfeiffer Vacuum GmbH), a home-built gasline (base pressure of 5.0 × 10–9 mbar) and an e-gun of in-house design.All experiments were carried out in a home built ultra-high vacuum setup as seen in 2(110) crystal was purchased from Surface-net GmbH and is of cylindrical shape with a diameter of 10 mm and a thickness of 2 mm. At two sides of the crystal symmetrical grooves were cut for mounting the crystal on a 1 mm thick tantalum plate. The interface between the metal and the single crystal is covered with a thin (0.025 mm) gold foil to ensure good thermal conductivity. The heating of the crystal was performed indirectly via resistive heating of two tungsten wires (0.38 mm in diameter), which were fixed on the sides of the tantalum holder. For the photochemical measurement, the sample holder was cooled by contact to a reservoir of liquid nitrogen to achieve temperatures of around 100 K. The temperature of the crystal was controlled by the calibrated readout of a twisted type-C thermocouple,29 which was inserted into a hole located on the side of the rutile single crystal without any adhesive. Crystal cleaning was done by repeated cycles of Ar+-sputtering, oxygen annealing and vacuum annealing and confirmed by AES. With this procedure a reduced, dark blue, conductive crystal was obtained which has a constant surface defect density of usually 10 to 15%.31The rutile TiO–1 to 700 K. For the photochemical measurements a Nd:YAG-pumped  dye laser (Lambda Physics) with a wavelength of 266.5 nm is used to excite electron–hole pairs. The laser spot lights the entire single crystal plane and the intensity was chosen with a pulse energy of 600 μJ per pulse, so no laser induced thermal heating effects were observed. Mass signals in the QMS of thermal and photochemically desorbing species were identified by cracking pattern analysis and were corrected by the different ionization sensitivities.Ethanol  was purified by pump-thaw cycles and flushing cycles of the gasline prior to use. Purity was confirmed by chamber backfilling and analysis with the QMS. The ethanol dosage was performed at a crystal temperature below 150 K and TPD experiments were conducted by heating the crystal with 1.2 K sm/z = 31) corresponds to the main fragment of ethanol and (m/z = 29) to that of acetaldehyde. For the latter, it has to be taken into account that this mass appears in the main fragmentation pattern of ethanol as well. The TPD spectra of the pure alcohol have already been extensively discussed in the literature.34 In general agreement, it is found that the majority of ethanol molecules desorb at temperatures below 300 K and, besides other features, another distinct peak above 400 K occurs. The trace representing acetaldehyde follows the same trend, but is proportionally lower in intensity. This trend only deviates at higher temperatures indicating that the signal only originates from the fragmentation pattern of ethanol with the exception of temperatures above 400 K, where also ethene is produced from dehydration.34For the elucidation of the mechanisms for the photocatalytic ethanol oxidation reaction, different desorption experiments were performed. The temperature programmed desorption (TPD) spectrum of 1 L of pure ethanol in the absence of UV light is shown in 2, photo-excitation at 110 K results in the accumulation of acetaldehyde at the surface. In agreement with the literature for highly covered crystal surfaces, the desorption of acetaldehyde occurs at lower temperature due to the repulsive interactions of the molecule with ethanol and other surface species.24 In contrast to the study of Idriss and coworkers performed at 300 K12 and in agreement with Yang and co-workers,24 oxygen dosing is not a prerequisite for a substantial yield in the ethanol photooxidation at lower temperatures. The amount of acetaldehyde produced is strongly dependent on the illumination time. versus illumination time at 110 K. A rapid rise with the photoexcitation is observed, which results in saturation at about 15% with respect to ethanol after 5 min.Upon irradiation of photons with energies above the band gap, another feature at 195 K appears in the spectrum depicted in in situ. 2 mass can also be monitored. However, only a small change in the signal with UV excitation is seen, which is rather attributed to cracking in the QMS than to the production of molecular hydrogen during reaction. Furthermore, no ethanol desorption is observed as is expected at this temperature. As seen in via a thermal process. After another dosage of ethanol at lower temperatures and subsequent irradiation at 222 K, a strong decrease in the acetaldehyde production is observed. The photochemical yield gets even lower for all successive dosage cycles, which hints to a deactivation mechanism of the catalyst. However, after ramping up the temperature to about 500 K, the activity of the catalyst can be completely restored.Since the desorption of acetaldehyde takes place at lower temperatures than that of ethanol, the photochemical reaction can be monitored 2 production is found in the photoreaction, it is observed that water molecules (m/z = 18) are leaving the surface in the TPD experiments in good agreement to Yang and co-workers.24 However, such water molecules may either originate from the photochemical reaction or the co-adsorption of residual water molecules from ethanol dosage. Thus, 2O trace of 1 L ethanol after 5 min UV illumination (a) and after the same time in the dark (b), to enable the discrimination between water formed by the photoreaction and water from co-adsorption. In both cases, an identical feature at 210 K is found, which can be attributed to H2O desorbing from O-bridge atoms of the semiconductor. However, in the case of the photoexcitation  of O2 indicated that no O2-species is bonded to remaining defect sites.37 The resulting TPD after 1 min of photoexcitation (2(110) surface. A similar behavior is observed for the desorption of acetaldehyde, which is in good agreement with the literature for molecular acetaldehyde.13 In contrast to the defect-rich surface, only the H2O desorbing from bridging O-atoms is observed. Although the photoreaction of ethanol takes place, a higher temperature signal of H2O as on the defect rich surface is not observed. This further demonstrates that the surface of the crystal is indeed defect free. The integral for the peak of 210 K significantly exceeds the one in 2O desorbing from the surface after the same time of illumination is similar for both surfaces, the defect-free and the defect-rich ones.To elucidate the role of defects in the reaction in more detail, a surface defect-free crystal is produced by annealing the crystal in oxygen at 300 K.citation  shows a 2(110) and always dissociatively in an oxygen vacancy.39 Thus, in the defect a chemical chemical reaction according to eqn (1) takes place, which results in the formation of an ethoxy species and a protonated Obr.Based on our findings and the existing studies in the literature, we propose the mechanism illustrated in When the semiconductor is irradiated by photons with energies above the band gap electron hole pairs are created (eqn (2)).41 The oxidation of alcohols is a hole mediated process.42 It can be described by eqn (3), in which a formal h+ reacts with the partly negatively charged ethoxy species, which undergoes an α-H elimination.Depending on the type of photochemical reaction, either electrons or holes govern the yield in the surface chemistry.via the oxygen atom,43 and can desorb at 195 K. The abstracted hydrogen either moves to the neighboring hydroxyl group to form water or results in the formation of another intermediate hydroxyl species, which eventually reacts to water and a bridging oxygen atom.44 In both cases, water molecules in an oxygen vacancy are produced, which block the defect and deactivate the catalyst. This mechanism fully supports the observed surface chemistry. The amount of water desorbing from defect sites shows a similar behavior to the formation of acetaldehyde . This is supported by the increase in the water desorption at around 225 K. A similar desorption temperature is found for water that is bound molecularly to a bridging oxygen atom.34Instead of filling vacancies, ethanol adsorbs on the oxide surface and dissociates, resulting in the ethoxy species and an adsorbed hydroxyl species. After the light-induced creation of electron hole pairs, photoholes initiate the formation of acetaldehyde. The reaction takes place 2(110) surfaces. The mechanism explicitly addresses the role of surface defects (such as oxygen vacancies) and the role of water as a by-product of the reaction. With this mechanism the experimental observations of the role of oxygen in surface preparation and deactivation as well as saturation of the reaction can be explained. This is facilitated by two different experimental methods. The first one uses TPD as a probe for the accumulation of photo-products at cold temperatures and the second one investigates the photoreaction at elevated temperatures above the desorption temperature of the photo-product. Our mechanism can not only be extended to other alcohols of different chemical structures, but may even supply potential reaction pathways for metal particle loaded semiconductor systems.In summary, we propose a stoichiometric reaction mechanism for the illumination-dependent photochemical oxidation of ethanol to acetaldehyde on TiO


Historically, the Bohai Sea is one of the most important fishing grounds in China. Yet, surrounded by one of the biggest economic rims of China, its ecological functions have been declining rapidly in recent two decades under the heavy anthropogenic impacts. The Laizhou Bay is the smallest one of the three main bays in the Bohai Sea. Owing to the rich brine deposits, chemical industries using brine as raw materials are booming in the southern coast of the Laizhou Bay, the scale of which ranks as the largest one in China. In order to monitor and assess the environmental quality, surface sediments were collected from the coastal waters of southwestern Laizhou Bay and the rivers it connects with during summer and autumn in 2012, and analyzed for heavy metals. Several widely adopted methods were used in the overall assessment of heavy metal pollution status and potential ecological risks in these sediments, and the data were analyzed to infer the main sources of the pollutants. The results showed that the remarkably high concentrations of heavy metals were almost all recorded in a small number of riverine sites. Cr, Cu, Ni and Zn were the main environmental threat according to the sediment quality guidelines. The marine area was generally in good condition with no or low risk from the studied metals and adverse effects on biota could hardly occur. Natural sources dominated the concentrations and distributions of Cu, Ni, Pb and Zn in the marine area. Our results indicated that heavy metal pollution was not a main cause of the ecological degradation of the Laizhou Bay at present. Although there is quite a controversy about the main causes and what kind of management measures should be taken, one fact that cannot be denied is that the eco-environmental condition of the Bohai Sea, which was once one of the most important fishing grounds in China, has degraded significantly under the influence of massive human activities . Many suExcessive input of heavy metals is a serious environmental problem in many coastal ecosystems around the world, and this has received extensive attention because many heavy metals are toxic, non-biodegradable in environment and easy to accumulate in organisms –7. The c2. It used to be one of the most important spawning and breeding grounds for many marine organisms in China. There are over a dozen small rivers running into the Laizhou Bay mainly from its southwestern coast such as the Guangli River, the Xiaoqing River, the Bailang River and so on. The Laizhou Bay is a continental climate area of the warm temperate semi-humid monsoon type. The annual average temperature is 11.9~12.6°C. The highest temperature appears in July, with the monthly average values of 25.9~26.4°C; the lowest appears in January, with the monthly average values of -2.8~-3.8°C. The average annual rainfall is 670~800 mm. Rainfall focuses between late June and early September, accounting for about 72%~76% of the overall rainfall. The Laizhou Bay is an irregular mixed semidiurnal tide area, and the flood and ebb last for 6.4 h and 6.0 h, respectively. The average tidal range of the Laizhou Bay is 0.9 m. Velocities of flood and falling tides are 29~37 cm s-1 and 29~39 cm s-1, respectively.The Laizhou Bay is one of the three major bays in the Bohai Sea, making up ~10% of its total areas, with a coastline length of ~320 km and a surface area of ~7000 kmIn recent years, the Laizhou Bay is under unprecedented threats because of the rapid development of urbanization and industrialization, overfishing and the unreasonable use of the coastline. Brine resources are rich in the southwestern coastal Laizhou Bay, due to which over 400 chemical enterprises are located along the southwestern coastline of the Laizhou Bay, forming one of the biggest manufacturing bases for chlor-alkali products in the world. The development of economy brings serious ecological threats to the Laizhou Bay, and its fishery resources have gradually declined. Coastal ecosystems that are close to industrialized communities, a situation that the Laizhou Bay is in, are likely to receive more heavy metal loadings from river discharges, inlets and estuaries filled with run-off from adjacent lands .The fact that sediments integrate the external environmental impacts makes them an essential source for information acquisition in major marine monitoring programs. To sum up, the purposes of this study are i) to investigate the spatial and seasonal distributions of the concentrations and fractionations of six heavy metals, i.e. Cd, Cr, Cu, Ni, Pb and Zn, that relate to the environmental quality assessment in the surface sediments of the southwestern marine area of the Laizhou Bay and the major rivers it connects with, ii) to estimate the anthropogenic influence, and iii) to assess the degree of contamination and the ecological risks of these heavy metals to the environment. The southwestern coast of the Laizhou Bay was chosen because it is the area of the Laizhou Bay facing the most serious threat from anthropogenic activities –14.This study did not involve endangered or protected species and no specific permissions were required for these locations/activities in this study. The specific locations of the present study were shown in The field sampling work of this research was carried out twice in 2012: early summer , which was before the peak period of the rainy season, and middle autumn , which was after the peak period of the rainy season. The sampling sites were arranged along the major rivers of this area extending from the land to the sea and formed five transects, covering about 15–20 km from the high tide mark to the land and about 10 km from the high tide mark to the sea . A totalThe information about the fractionations of metals in the surface sediments was obtained by a sequential extraction procedure reported by Rauret et al. . The fou3 and HClO4 (5:2:1) [The total concentration of each studied metal in all samples was obtained by digesting an aliquot of freeze-dried, homogenized and ground sediment with the mixture of concentrated HF, HNO (5:2:1) . The conAnalytical methods and results of the total organic carbon (TOC), grain size and moisture content (MC) of the samples have been described in previous publications , 22–24. 3 (w/w) for at least 2 days, followed by soaking and rinsing with de-ionized water.The analytical data quality was guaranteed through the implementation of laboratory quality assurance and quality control methods, including the use of standard operating procedures, calibration with standards, analysis of reagent blanks, and analysis of replicates. The quality of the analytical procedures was tested by recovery measurements on the Chinese national geostandard samples (GBW-07333 and GBW-07314). The results were consistent with the reference values, the differences were all within ±10%, and the precision, expressed as the relative standard deviation (RSD), ranged from 5% to 10%. The precision of the analysis of standard solution (RSD) was better than 5%. All analyses were carried out in duplicate, and the results were expressed as the mean. All reagents were analytical or guaranteed grade. All the labwares  were pre-cleaned by soaking in 10% HNOIn this study, two sediment quality guidelines (SQGs) , 26 and The National Standard of China GB18668-2002  has defiThreshold effects level (TEL) and probable effects level (PEL) are guidelines widely used to assess bio-toxic risks of sediments . TEL is Cx is the sediment concentration of component x, PELx is the PEL for component x and n is the sum of components. For marine sediments, the mean PEL quotients of <0.1, 0.11–1.5, 1.51–2.3 and >2.3 indicate that the combined effects of contaminants have an 8%, 21%, 49% and 73% probability of being biologically toxic, respectively [In view of the fact that contaminants always occur in sediments as complex mixtures, the mean PEL quotient method has been proposed and adopted to determine the possible biological effect of combined toxicant groups by calculating the mean quotients for a range of contaminants using the following formula , 36:MeaStatistical methods were applied to process the analytical data in terms of the distribution and relationships among the studied parameters. Pearson’s correlation coefficient analysis was performed to identify the relationship among heavy metals in sediments and their possible sources. The principal component analysis (PCA) was performed to extract significant principal components (PCs) and further reduce the contribution of variables with minor significance. The PCA was performed with varimax rotation with Kaiser Normalization to generate varifactors (VFs) in this study. The commercial statistics software package SPSS version 19.0 for Windows was used for statistical analyses mentioned above. Scatter graphs were drawn using Origin version 8 to determine whether there were significant differences in sources between each studied metal in different seasons. The agglomerative hierarchical clustering (AHC) analysis was conducted on the normalized data set using Ward’s method with Euclidean distances as a measure of dissimilarity to assess the interrelationships among the sampling sites. The XLSTAT software (version 2013) was used in the AHC analysis.-1) were slightly higher than that in the riverine sediments (17.9 μg g-1) in autumn, the mean concentrations of all the other studied metals in the marine sediments were much lower than that in the riverine sediments in both seasons. The highest concentrations of Pb in both seasons were found in the surface sediment of site H1 which was located in the marine area , and the concentrations of Pb in the surface sediments of all the rest of marine sites and most of the riverine sites were much lower, and almost all lower than its corresponding value in the UCC, i.e. 20 μg g-1  in sediments of these rivers might be attributed to the point sources such as industrial effluent and domestic sewage discharged directly into the rivers  and the -1; autumn, 548.4 μg g-1)  . Extremeectively . River bn summer .So on the whole, there was no significant difference between spatial distribution of the heavy metals in the two sampling periods, and very high concentrations of certain heavy metals in some riverine sediments could be attributed to intensive anthropogenic activities. The mean concentrations of all studied metals in the marine sediments increased slightly from summer to autumn. This was probably because most of the studied rivers are seasonal rivers, and the flows of these rivers increased during the rainy season, so larger amounts of heavy metals were carried from the land to the Laizhou Bay which caused the increase of heavy metal concentrations in the marine sediments in autumn.Compared with the strong mobility of water, heavy metal contents in sediment are relatively stable. So heavy metal contents of the two sampling periods could largely reflect the situation of the two seasons. To further seek the relationships between the data of the two sampling periods and find out whether there were seasonal differences in sources, scatter graphs were made for each of the studied heavy metals . It cleaThe mean concentrations of Cd and Cr in both the riverine and marine sediments in both seasons were clearly higher with respect to their corresponding values in the UCC; the mean concentration of Cu in the riverine sediments in summer was higher comparing with its corresponding value in the UCC, while its mean values in the riverine sediments in autumn and in the marine sediments in both seasons were lower comparing with its corresponding value in the UCC; the mean concentrations of Ni and Zn in the riverine sediments in both seasons were higher with respect to their corresponding values in the UCC, while their mean values in the marine sediments in both seasons were lower than their corresponding values in the UCC; the mean concentrations of Pb in both riverine and marine sediments in both seasons were very close to its corresponding value in the UCC .Among the three bays of the Bohai Sea, the mean concentrations of heavy metals in surface sediments of the SW Laizhou Bay were the lowest. In addition to the influence of human activities, particle size effect was likely to be one of the main factors for this phenomenon. Surface sediments of the studied marine area were made up of silt-sand or sand-silt . CompariThe correlation matrix for the concentrations of the geochemical parameters studied is shown in The toxicity and mobility of heavy metals in sediments vary greatly among different geochemical forms, and heavy metal fractionation offers a more realistic evaluation of their actual environmental impact , 52. FraThe percentages of heavy metal concentrations that were extracted in each step of the sequential extraction procedure used in this study were presented in For the riverine sediments, the mean percentages of Cd fractions in both seasons and Zn fractions in summer followed the order of F4 > F1 > F2 > F3, the mean percentages of Cr and Cu fractions in both seasons and Pb fractions in summer followed the order of F4 > F3 > F2 > F1, the mean percentages of Ni fractions in both seasons followed the order of F4 > F3 > F1 > F2, and the mean percentages of Pb and Zn fractions in autumn followed the order of F4 > F2 > F3 > F1.For the marine sediments, the mean percentages of Cd and Zn fractions in summer followed the order of F4 > F1 > F2 > F3, the mean percentages of Cd and Ni fractions in autumn followed the order of F4 > F1 > F3 > F2, the mean percentages of Cr and Cu fractions in both seasons followed the order of F4 > F3 > F2 > F1, the mean percentages of Ni fractions in summer followed the order of F4 > F3 > F1 > F2, the mean percentages of Pb fractions in both seasons and Zn fractions in autumn followed the order of F4 > F2 > F3 > F1, and the mean percentages of Zn fractions in summer followed the order of F4 > F1 > F2 > F3.Cd had the highest mean percentage of the acid soluble fraction among the studied metals with the values of 16.3% and 28.6% in summer in the riverine and marine sediments, respectively, and the corresponding values in autumn were 20.7% and 21.8%, respectively. As already mentioned in the previous section, Cd is a typical anthropogenically discharged element and enters the aquatic environment mostly through anthropogenic activities . The perIn both seasons, the percentages of the four fractions of Cr and Cu followed the same order F4 > F3 > F2 > F1 in both the riverine and marine sediments. Considering the whole studied area, more than 85% of Cr on average was found in the residual phase in both seasons, while the proportions of the residual fraction for Cu were not that high and the mean values were 71.6% and 67.0% in summer and autumn, respectively. On average, the non-residual Cr and Cu were identified being the highest in the oxidizable fraction in both seasons, and their average percentages in this fraction were clearly higher in the riverine sediments than in the marine sediments. Relatively higher percentages of oxidizable Cr and Cu were recorded at sites XQH3 and XQH4 in both seasons and at sites DH1 and DH2 in autumn. In addition, relatively higher percentages of oxidizable Cu were also recorded in all the three sites in the Yihong River and in MH1 in summer. Generally, the proportions of Cr and Cu in the acid soluble fraction were very low, especially for Cr which was less than 1% of the total concentration in both seasons.High proportions of residual fraction with a mean value of >70% in both seasons were also observed for Ni. The distribution characteristics of Ni in the four studied geochemical fractions in most sites were similar. Only the site YHH1 showed an obviously higher percentage of non-residual fractions in autumn (64.3%).Pb had the highest proportion in the reducible fraction among the six studied metals with the mean values of 23.7% and 23.5% in summer in the riverine and the marine sediments, respectively, and the corresponding values in autumn were 26.7% and 22.5%, respectively. Like those of Cr and Cu, the mean percentage of Pb in the oxidizable fraction in the riverine sediments was much higher than that in the marine sediments. This could be explained by the fact that there were more organic matters and sulfide for these metals to combine with and lower redox potential in the riverine sediments than in the marine sediments in the studied area .-1 and 1605.4 μg g-1, respectively, indicating a very high potential ecological risk.The mean percentages of Zn in acid soluble fraction in the riverine sediments were much higher than in the marine sediments, which indicated the obvious spatial difference in the anthropogenic impact on the potential mobility of Zn in the studied area. Generally consistent with the spatial distribution characteristics of the studied metals in total concentrations, the relatively higher percentages of Zn in acid soluble fraction were mainly distributed at some sites in the Yihong, the Xiaoqing, the Mi, the Di and the Yu Rivers. A fact that should be noticed is that, although the percentages of Zn in acid soluble fraction in the surface sediments of the sites DH1 and DH2 in autumn were not that high , owing to its high values in total concentration, its concentrations in this fraction were up to 107.2 μg gAs shown in The concentrations of Cr and Ni in the surface sediments of most sites exceeded their corresponding TEL values. The concentrations of Cr at seven riverine sites in summer and six riverine sites in autumn exceeded the corresponding Class I upper limit; they exceeded Class II upper limit in XQH3 and XQH4 in both seasons, and exceeded PEL value at XQH3 in both seasons and at XQH4 in summer. The concentrations of Ni in two riverine sites in summer and four riverine sites in autumn exceeded the corresponding PEL value. Most of the values were also recorded in some of the following rivers: the Yihong River, the Guangli River, the Xiaoqing River, the Mi River, the Yu River and the Di River.-1) and DH2 (13213 μg g-1) in autumn, which were even much higher than the corresponding value of the Class III upper limit in the Chinese marine sediment quality standard.In terms of the concentrations of Cu and Zn, the surface sediments for most of the sites were also in good condition especially in the marine region in both seasons. Except for the concentrations of Cu at the marine sites K3 (summer) and J4 (summer and autumn) which slightly exceeded the corresponding TEL value, the concentrations of Cu and Zn in sediments of all the rest of the marine sites did not exceed their corresponding TEL values and Class I upper limits. The concentration of Cu exceeded both the corresponding PEL value and Class II upper limit at the site YHH2 in summer. The concentrations of Zn exceeded its corresponding PEL value or Class II upper limit at ZMH1, XQH3 and XQH4 in one or both seasons. Extremely high concentrations of Zn were observed at DH1  and no RAC value exceeded 10%. The highest RAC value of Cr was recorded at site J3 in summer, but the value was only 6%. Most RAC values of Cu and Pb were between 1% and 10%, indicating a low risk from them; the highest values of both Cu (38.3%) and Pb (11.8%) were recorded at L3 in autumn.The majority of RAC values of Ni fluctuated around 10%, indicating a status of low risk to medium risk. The relatively higher RAC values of Ni were recorded at sites YHH1 (28.6%) and MH2 (30.5%) in summer, indicating a status of medium risk and high risk, respectively.Most RAC values of Zn in the riverine sediments were between 10% and 30% indicating a medium risk. The relatively higher RAC values of Zn were distributed at the sites in the Yihong, the Xiaoqing, the Mi, the Di and the Yu Rivers. The highest RAC value of Zn was recorded at MH1 (56.6%) in summer which showed a very high risk. Compared with the other marine sites, H3 in summer had the highest RAC value of Zn (29.6%), and the risk level was medium.It is worth noting that although the acid soluble fraction of Cd occupied considerable proportions of the total contents, the total concentrations of Cd in most sites were very low. The TEL value or the Class I value of Cd was exceeded in a few riverine sites, so the ecological risk of Cd might not be that serious. Similarly, percentage composition of acid soluble Zn was not that high as Cd, but the total concentrations of Zn in surface sediments of some sites were extremely high, especially in DH1 and DH2 in autumn , they stIgeo and EF of Cr, from which it can be concluded that Cr has obvious enrichment and ecological risk. However, RAC showed there was little possibility of contamination caused by Cr. EF and Igeo indices were calculated mainly based on the total concentration and the back ground value of a given metal, whereas RAC was based on the chemical form of a given metal neglecting its total concentration. So the different basic principle of these indices might lead to the differences in evaluation results. It is generally accepted that the fractionation can give more information on the bio-availability and bio-toxicity of a certain metal than the total concentration, but it is also difficult to produce any ecological risk if bio-availability content cannot meet the threshold value, so the total content is also very important. Therefore, a variety of evaluation methods should be used to reflect the real situation.According to the three sediment quality indices above, ecological risk in the riverine sediments was significantly higher than in the adjacent marine area, and the relatively higher risk was recorded in some sites of the Yihong, the Guangli, the Xiaoqing, the Mi, the Yu and the Di Rivers. All indices indicated that Cd showed the highest ecological risk in the studied area especially in the riverine sediment, and Pb showed the lowest ecological risk, and the ecological risks of Cu, Ni and Zn were between them. There was a high consistency between PCA can be used to reduce data and extract a smaller number of independent factors  for analyzing the relationships among observed variables. This method has been widely applied to the identification of pollution sources and the apportionment of natural versus anthropogenic contributions , 63, 64.In summer, PC1 which explained 39.3% of the total variance was significantly and positively related to all the heavy metals and TOC, but was not significantly related to Al and Fe which are indicators of terrigenous detrital sources , 65. EF In autumn, PC1 which explained 45.2% of the total variance was significantly and positively related to all the heavy metals and Al/Fe. EF values also indicated that significant portions of metals were delivered from anthropogenic sources in autumn . Thus PCFor the comparison purpose, PCs for surface sediments in the Liaodong Bay and the southern Bohai Bay (hereinafter referred to as the Bohai Bay for short) were also shown in Considering all the evidence, the overall situation about geochemical characteristics of heavy metals in the surface sediments of the studied area might be as follows. The sampling time in summer was before the peak period of the rainy season, so only a small amount of heavy metals from natural rock weathering sources could be carried into the aquatic environments by rainwater. And the main sources were anthropogenic sources such as effluent and sewage runoff, traffic activities, the burning of fossil fuels and boat maintenance and repair, and/or biogenic sources such as deposition of biological debris. The sampling time in autumn was after the peak period of the rainy season, so a large amount of heavy metals from natural rock weathering sources might have been brought into the rivers and the marine region by rainwater. Therefore, anthropogenic sources, terrigenous detrital sources and biogenic sources all made important contributions to the geochemical characteristics of heavy metals in the sediments in autumn.In the surface sediments of the southwestern coastal Laizhou Bay, the total concentrations of heavy metals in the riverine sediments were much higher than in the marine sediments, and the relatively higher concentrations of metals were detected at some sites of the Yihong, the Guangli, the Xiaoqing, the Mi, the Di and the Yu Rivers.It was found that all the studied metals mainly existed in residual fractions, yet spatial differences were very significant and non-residual fractions dominated their fractionations at some riverine sites. Although Cr had the lowest percentage in acid soluble fraction, the most labile fraction, with the mean value of less than 1% in both seasons, it was obviously enriched at most of the sites; meanwhile, as the most enriched heavy metal, Cd had the highest percentages in the acid soluble fraction among the studied metals with the mean values of 20.5% and 21.1% in summer and autumn, respectively, while its low total concentrations made it hard to cause negative effects to the environment according to the sediment quality guidelines.Cr, Cu, Ni and Zn were the main pollutants in the riverine sediments according to the sediment quality guidelines. The quality of the marine sediments was generally in good condition, and there was no significant increase in the concentrations of the studied metals compared with the previous studies in surface sediments of the Laizhou Bay. The heavy metals obviously had different sources in different seasons. In summer, the metals were mainly from anthropogenic and biogenic sources; in autumn, the anthropogenic activities and terrigenous detrital were the main sources. This study indicated that, up to now, there was no clear sign that heavy metal pollution was correlated with the ecological degradation of the Laizhou Bay.S1 Table(PDF)Click here for additional data file.S2 TableF1: acid soluble fraction; F2: reducible fraction; F3: oxidizable fraction; F4: Residual fraction.(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.S5 Table(PDF)Click here for additional data file.


Background. The aim of the research was to estimate the frequency of the locoregional breast cancer recurrence appearance, the recurrence-free period continuance, and the 3- and 5-year survival depending on the scope of the surgical intervention, menstrual profile, and histological and molecular-biologic characteristics of the primary tumor. Patients and Methods. Among 218 patients with a breast cancer, 99 patients had breast-conserving surgery (BCS) and 119 underwent radical mastectomy (RME); all patients had regional lymphatic nodes dissection. The size and the primary tumor differentiation degree, metastasis presence in the regional lymph nodes, ER expression, PR, and Her/2neu were assessed as the prognostics factors. Results. It was defined that the locoregional recurrence appearance frequency in patients with BCS turned out to be 13%, and in patients after RME it turned out to be 9%; the recurrence-free period continuance was 53 ± 8 months and 56 ± 10 months, respectively. Conclusions. The locoregional cancer recurrence frequency is higher in women with the menstrual function being preserved at the moment of the primary tumor detection than in postmenopausal patients and also in patients having the hyperexpression of the Her/2neu. The ipsilateral cancer recurrence decreases the 3-year survival by 7,1% and the 5-year one by 20,3%, respectively.  According to the GLOBOCAN 2012 v1.0, in 2012, worldwide there were 14.1 million new cancer cases, 8.2 million cancer deaths, and 32.6 million people living with cancer (within 5 years of diagnosis). 57% (8 million) of new cancer cases, 65% (5.3 million) of the cancer deaths, and 48% (15.6 million) of the 5-year prevalent cancer cases occurred in the less developed regions. Breast cancer is the second most common cancer in the world and, by far, the most frequent cancer among women with an estimated 1.67 million new cancer cases diagnosed in 2012 , where it is the most frequent cause of cancer death in women in less developed regions , and it is the second cause of cancer death in more developed regions  after lung cancer [The successes in diagnostics and chemoradiotherapy of the breast cancer at the present stage of the oncology development lead to the reconsideration of the surgical treatment methods. At first, Maddox et al.  showed tn = 99) the patients who underwent the BCS were referred , and to the second group (n = 119) we referred the patients who passed RME (RME by Madden: 91 and RME by Patey-Dyson: 28). In their turn, groups 1 and 2 were divided into 2 subgroups. To group A were referred the patients without breast cancer recurrence and to group B the patients with the recurrence appearance. Patients were assigned to the BCS with an attempted margin of 1 cm of healthy tissue. Margins were routinely inked to assess the microscopic completeness of the lumpectomy. The criteria to choose for each patient BCS or RME are tumor size, extensive DCIS, tumor margins, tumor location, need for radiation, risk reduction, and individual needs and preferences. Reasons to avoid BCT include multiple tumors, extensive tumor, and contraindication for radiation.218 patients had been examined at the age of 31 to 92  years, who passed BC treatment course at the oncological clinic of the National Medical University in Kiev Oncology Municipal Hospital in 2004–2009. Among them, 162 patients were treated from primary BC in 2004-2005, and 56 patients were treated from BC recurrence in 2004–2009. The patients were divided into 2 groups: to the first group  and placed on the glasses treated with poly-L-lysine. Then, the material was treated according to the standard procedure using the following antibodies: ER-clone 1D5, PgR-clone 636, and Her-2/neu-clone Cb11. The results interpretation was done by immunohistochemical reaction using the nuclear reaction qualitative assessment: the negative “–,” the low positive “+,” moderately positive “++,” strongly positive “+++,” and quantity of dyed tumor cells in %.The cuts of 4-5 In making an assessment of Her-2/neu expression, the intensity of cytoplasmic basal membrane coloring was pointed out: the reactions “−” and “+,” the absence of hyperexpression, and the reaction “+++,” hyperexpression of Her-2/neu. The presence of the hyperexpression Her-2/neu in cases of “++” reaction is conducted with the help of hybridization method in situ using the fluorescent marker FISH (fluorescent in situ hybridization). The investigations were conducted at the pathohistological laboratory at Kiev Municipal Oncology Hospital.The patients received adjuvant systemic treatment and radiotherapy according of the St. Gallen International Breast Cancer Conference recommendations (2001–2005).The histopathological diagnosis of breast recurrences was reviewed and compared with that of the initial tumor taking into account cytological, morphological/architectural, and stromal patterns, histological grade, and immunohistochemical staining . The majority of these parameters had to be similar for a given lesion to be declared a true recurrence.K tables analysis were used.In estimating the influence of the axillary node involvement, histological grade, tumor size, and immunohistochemical staining , the fourfold tables analysis method and the 2 × The connection between the LR BC and the menstrual function condition of the patients at the primary tumor detection was defined via 2 × 2 tables' analysis.The Kaplan-Mayer method was used to estimate the patient's survival rate .p) 0,05. But in the BCS group the axillary node involvement increases the frequency of the ipsilateral recurrence of the breast cancer.The tumor size, axillary node involvement, and histological grade are the predictive factors of the disease run . In the K table analysis method [The results of the immunohistochemical examination are shown in the s method . It was p > 0,05) and differences in 5-year survival between groups are statistically significant .The assessment procedure of Kaplan-Meyer was used to evaluate the overall patients' survival. Three-year survival rate in patients without BC recurrence was 87,6% and the 5-year survival rate was 82,8%. Three- and 5-year survival in patients with BC recurrence of the BC corresponded to 80,5% and 62,5%, respectively . The difThe era of conserving surgeries in breast cancer started in the 1970s. U. Veronesi in Milan Cancer Institute  and B. Fisher in The Abramson Cancer Center of the University of Pennsylvania (USA) proposed independently of each other to perform the conserving surgery in breast cancer. In 1969, results of randomized studies to compare radical mastectomy with breast-conserving surgery, which was termed “quadrantectomy,” were approved by the World Health Organization Committee of Investigators for Evaluation of Methods of Diagnosis and Treatment of Breast Cancer . The recThe afterward published results of the above investigations had not demonstrated the appreciable difference of the late fates. However, in patients after the BCS, the probability of the locoregional recurrence appearance is higher compared with the patients who have been undergone the radical mastectomy. The recurrence appearance requires another surgical intervention, oftener than the mastectomy which aligns the cosmetic an d esthetic effect reached at BCS. Besides, the appearance of the regional breast cancer decreases the 3- and 5-year survival.The important thing in the clinical practice is the drawing distinctions between the real recurrences and the newly occurred ipsilateral tumors. This is due to the fact that the newly occurring breast cancer is susceptible to the X-ray therapy and standard schemes of the chemotherapy, whereas the recurrent tumor is chemo- and radio-resistant and requires the adjuvant treatment modification , 14, 15.The causes of the ipsilateral recurrences development could be the following ones: tumor cells expansion along the muscle fiber, fascial plates, vessels, and nerve and perineural crevice tunics; the tumor could have plural rudiments , which are the causes of underestimation of the process expansion; it could be rested in the edges the microscopic normal, but genetically changed cells, which will initiate the recurrent tumor development.The presence of the established risk factors of breast cancer recurrence development in patients  requires more strict control of the adjuvant treatment; the main efforts must be directed to the early recurrence detection and the usage of the up-to-date methods of diagnostics  and biopsy at the susceptible recurrent focuses.The surgical intervention volume does not affect the frequency of the locoregional breast cancer recurrence appearance.The recurrence-free period duration in patients who have been done the breast-conserving surgery does not essentially differ from the patients who have been undergone the mastectomy.In patients after the breast-conserving surgery, the presence of metastases in the regional lymphatic nodes and the hyperexpression Her/2neu in the primary tumor cells is associated with the higher risk of the locoregional recurrence.The regional breast cancer appearance decreases the 3-year survival by 7,1% and 5-year survival by 20,3%.


Although chronic myeloid leukemia (CML) is characterized by the Philadelphia (Ph) chromosome, which is the result of t q34;q11) or its variants, 10%-20% of cases have additional cytogenetic abnormalities. The most common additional abnormalities are loss of the Y chromosome, +8, +Ph, and i(17q). Since these additional chromosome abnormalities are signs of disease progression, it is important to perform cytogenetic analyses periodically in patients with CML [1 or its We have published our results on clonal chromosome abnormalities other than the Ph chromosome in Ph+ and Ph- cells of CML patients who were followed in our center a few years ago ,3. MonosAll 3 patients in this study were under imatinib therapy except for patient 2, who was receiving interferon at the time of the first sampling. Conventional cytogenetic techniques were performed to examine the marrow samples. GTL-banded metaphases were examined according to International System for Human Cytogenetic Nomenclature guidelines . Twenty In the first 3 samples of patient 1, monosomy of chromosomes 8, 10, and 20 was confirmed by FISH. In the fourth sample of this patient, we performed FISH for chromosomes 10 and 20 despite their absence in the karyotype to see whether there was a hidden monosomy that we could not show by karyotyping. FISH indeed revealed a hidden monosomy for chromosome 20, but not for chromosome 10. In the first 2 samples of patient 2, monosomy of chromosome 17 was observed in cytogenetic analysis and confirmed by FISH. However, in the third sample, -17 could be shown neither in the karyotype nor by FISH. Notably, percentages of -17 obtained by cytogenetics and FISH were compatible in each of the samples. In the first sample, -17 was detected cytogenetically in 3 out of 12 cells (25%), and it was found in 46% of the interphases by FISH. In the second sample, -17 was found in 12% and 31% of the cells in cytogenetic and FISH analysis, respectively. In the third, it was absent in cytogenetic preparations as well as in FISH study. -17 may be an important candidate marker to be followed by FISH in the course of CML since it is one of the additional minor-route chromosome abnormalities in the clonal evolution of Ph+ CML [FISH results were in line with those of cytogenetics in some samples while not in others. This, once again, highlights the importance of concurrent use of different techniques  in cancer samples to increase the detection capability and improve the reliability of the results. Studies with larger numbers of patient samples and longer follow-up are required to establish the impact of certain monosomies on the disease course.


The 2014 ESC/EACTS Guidelines on myocardial revascularization, define the SYNTAX Score, as a risk stratification model for the planning the type of treatment. The SYNTAX score was developed to grade the anatomical complexity of coronary lesions in patients with left main or three-vessel disease.To assess whether the guidelines, based on SYNTAX Score, are being followed in a cardiovascular unit in the south of Brazil, in which the decision is made by a Heart Team.A retrospective blind study was conducted evaluating 395 coronary angiographies, from January 2013 to August 2014. The insertion criteria was the angiography of all patients under investigation for coronary disease. The exclusion criteria were the angiographies of patients that already had any type of percutaneous transluminal angioplasty (PCI) or coronary artery bypass grafting (CABG). The angiographies were evaluated and classified according the SS, in group A (score ≥ 22), B (score 23-32) and C (score ≤ 32). An independent blind observer checked the type of treatment performed and the percentage of each of those three groups.The coronary angiographies, of the 395 patients were analyzed and showed an average SS of 9.95 ± 10.45.The table below shows the population of each group:From the 395 patients assigned to the study, 121 patients underwent PCI and 42 CABG. The remainder 232, underwent medical treatment. All patients undergoing CABG were in the C group and part of B; of patients undergoing PCI, 7 (5.79%) belonged to the B group and 114 to group A (94.21%).The guidelines have been followed, in a unit in which a Heart Team decides what type of treatment should be considered, because the patients underwent the recommended treatment, based on the SYNTAX Score.


A total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.The study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.The observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism. Autism is a lifelong disorder characterized by disrupted development of social and communication skills and restricted, repetitive, and stereotypical patterns of behavior, interests, and activities. In nearly 50% of individuals later diagnosed with autism, functional alterations are noted at between 14 and 24 months, and alterations are observed in all three diagnostic functional domains at 24 months of age [In the past three decades, numerous studies have been conducted on the trajectory of brain overgrowth, differences between the sizes of individual brain structures and regions, and the abnormal number and size of neurons in the brain in autism spectrum disorder (ASD). A large cluster of studies has focused on distortion of the trajectory of brain growth, which may involve modifications of the brain and of brain structure volumes as well as of the number of neurons. A rapid increase in head circumference at 1–2 years of age -7 followp = 0.054), but the contribution of this small population of neurons to the volume of this cortical region is marginal. However, the majority of reports show that the numbers of many neuronal populations in the brain structures of individuals with autism are unmodified [Individual brain structures have distinct developmental profiles from the trajectory of brain development -20. Growmodified -28 or remodified -34.This project was designed to partially reduce the limitations of research outcome due to the small size of the cohort examined with (a) different methods of tissue preservation and evaluation and (b) concentration of the study on a few brain regions. Four parameters—brain weight, the volume of brain structures’ cytoarchitectonic subdivisions, the total number of neurons, and the numerical density of neurons per region of interest—were selected to detect developmental and age-associated alterations in the brains of 14 individuals diagnosed with autism and 14 control subjects. The aim of the study of 14 brain structures and their 24 subdivisions  including subcortical and cortical structures, cerebellum, and brainstem was to identify a global pattern of alterations and to establish whether the function of altered structures matches the behavioral alterations that are diagnostic for autism.Originally, 39 brains were assigned to this study of developmental abnormalities in autism, including 21 brains of subjects diagnosed with autism and 18 control brains. Application of clinical inclusion criteria and neuropathological exclusion criteria reduced the size of this cohort to 28 subjects, comprising 14 subjects with autism and 14 age-matched control individuals. Two cases did not meet the Autism Diagnostic Interview-Revised (ADI-R) .The clinical diagnosis of autism was confirmed by a postmortem application of the ADI-R. Results of the ADI-R and the clinical characteristics of this cohort have been summarized by Wegiel et al. . Eight sNeuropathological evaluation revealed various types of developmental abnormalities in 13/14 brains of individuals diagnosed with autism (93%), which were summarized in our previous report , includiThe study has been approved by the institutional review board (Application # 463) of the New York State Institute for Basic Research in Developmental Disabilities.Tissue samples, demographics of individuals with autism and control subjects, brain weight, and changes during processing were characterized in our previous report . In shorThe anatomical boundaries of the examined brain structures and their cytoarchitectonic subdivisions were described in detail in our previous report . DelineaThe rostral striatum is divided into the caudate nucleus and the putamen by the internal capsule. The border between the nucleus accumbens, the caudate nucleus and the putamen was arbitrarily defined by a line perpendicular to the midline of the internal capsule at its ventral end . The numIn Ammon’s horn the number of neurons was estimated in the pyramidal layer in sectors CA1–4. The CA1 sector pyramidal neuronal layer extends from the subiculum to the CA2 sector as a thick band of medium size pyramidal neurons. Two features distinguish the CA2 sector: a compact arrangement of large pyramidal neurons and the lowest thickness of this layer. The size of neurons in the CA3 and 4 is similar, but parallel arrangement of neurons in the CA3 sector distinguishes CA3 from randomly dispersed neurons in the hilus, identified also as CA4 sector ,44. The The neurons were distinguished from glial cells by using histological features revealed by cresyl violet staining, including neuron size, shape, and spatial orientation typical for specific layers, sectors, and brain nuclei, as well as the pattern of staining of nuclear chromatin, the distinct nucleolus in the majority of examined neuronal populations, and cytoplasm morphology. Small and round nuclei with uniform, intense staining of nuclear chromatin distinguished oligodendrocytes from astrocytes with large, round nuclei with a small amount of dispersed chromatin and an undetectable nucleolus.Volume evaluation and counting of neurons were performed using a workstation consisting of an Axiophot II  light microscope with Plan-NEOFLUAR objectives—1.25 × , 2.5 × (N.A. 0.075), 5 × (N.A. 0.15), 20 × (N.A. 0.5), and 40 × (N.A. 0.75); a specimen stage with a three-axis, computer-controlled stepping motor system ; a CCD color video camera ; and stereology software .3) was estimated in the cerebellar cortex, including molecular and granule cell layers. An optical fractionator systemic random sampling scheme was applied . Twelve equidistant serial sections were used for neuronal counts in the anatomical subdivisions of the amygdala; 10 in the substantia nigra; 14 in cornu Ammonis sectors CA1–CA4; 13 in the claustrum; 16 in the magnocellular basal complex; 6 in the thalamus, entorhinal cortex, globus pallidus, and nucleus accumbens; 9 in the caudate nucleus and putamen; 8 in the cerebellum and in the inferior olive; and 11 in the dentate nucleus. The bias related to sectioning defects was reduced by application of 5-μm-wide top and bottom guard zones. The results of examination of the cytoarchitectonic subdivisions are presented as the mean number of neurons per mm3  and the total number of neurons per region of interest. The sizes of the grid and of the virtual counting space were adjusted to the size and shape of the examined regions. The number of virtual counting spaces ranged from 62 per subdivision per case in a very small subdivision such as the fifth layer in the entorhinal cortex  to 1953 in the globus pallidus with a low neuronal numerical density .The parameters and procedures that were applied to estimate the volume of brain regions and the number of neurons are summarized in Table The mean volumes, number of neurons, and neuronal density of structures in autistic and control brains were compared in analyses of covariance (ANCOVAs) and repeated measures analysis of variance in which brain weight and, for neuronal counts and density, log age, post-mortem interval, and days of fixation were entered as covariates. Pearson correlations were computed for age and the total number and density of neurons in the autistic and control cohort.To test the hypotheses that structures differ in the degree to which autism affects, first, the number of neurons in the structure and, second, the volume of the structure, we conducted repeated measures analyses of variance with structure and autistic status as factors, with the potential confounders of brain weight, post-mortem interval, days of fixation, and log age entered as covariates. The significant interaction of structure with autistic status in each case indicates that autism’s effect upon the number of neurons  and upon structural volume  differs among the structures examined.3, 2,365 mm3, and 1,727 mm3, respectively) to the smallest inferior olive (59 mm3) . The nucleus accumbens was larger by 34% . However, analysis of alterations in 4- to 8-year-old children did not reveal a significant difference between the affected and control groups. The finding of a significantly larger caudate nucleus and nucleus accumbens only in 9- to 60-year-old individuals with autism suggests that the difference may be a result of changes during adolescence/adulthood.In the control group, the volume of 14 brain structures and their 24 subdivisions ranged from the largest structures, such as the thalamus, putamen, and caudate nucleus , and the percentage of the cerebellar cortex occupied by these two layers  in the group with autism did not reveal a significant difference in comparison to the control group . The mean volume of white matter was almost the same in the affected and control cohorts , as was the percentage of the cerebellar volume occupied by white matter . Also, the volume of cerebellar nuclei , including the largest dentate nucleus , did not reveal a significant difference between individuals with autism and control subjects.The mean volume of the examined cerebellar hemisphere was almost identical in the affected and control groups: 31,779 mmp < 0.013 not corrected for log of age, brain weight, postmortem interval, and days of fixation). In two affected cases, neuronal deficit in the entorhinal cortex was detected without the support of morphometric methods, as the paucity of focal stellate neurons in disorganized islands that were smaller than normal. However, a reduction of the mean total number of neurons to 788,879 and the shift of significance to p < 0.007 after removal of these two cases from the analysis indicates that these focal developmental defects contribute less to the decrease of the mean number of stellate neurons than do diffuse deficits not detectable without morphometric support.Application of the fractionator method to determine the total number of neurons in 15 brain structures and their 16 cytoarchitectonic subdivisions in control subjects Table  revealed3 in the globus pallidus to 40,031/mm3 in the nucleus accumbens. In the group with autism, a significantly lower numerical density of neurons was detected in three brain regions: the lateral nucleus in the amygdala , putamen , and nucleus accumbens . Box plots demonstrate that in the majority of subjects with autism the numerical density of Purkinje cells, neurons in the lateral nucleus in the amygdala, nucleus accumbens and in the putamen is less than the median numerical density in the control group  in the hypoplastic area than in the control cerebellar cortex. The total number of Purkinje cells was 42% less in this case (7.1 million) than the mean total number in the examined hemisphere of other subjects with autism and 65% less than in the control group.The volume of cerebellum and cerebellar subdivisions as well as the number of neurons was estimated after exclusion of records for brain samples of two subjects with autism: one with focal defects of cresyl violet staining related to poor fixation, and the second because of focal dysplasia. A 60-year-old subject with autism and clinically diagnosed disturbed movement coordination and postmortem-detected severe hypoplasia of cerebellar lobes I-IV  was exclp < 0.0001) in the group with autism (12.1 million) than in the control cohort (16. million) (25% deficit). The minimal number of Purkinje cells in the examined hemisphere in the control group was 11.4 million, but in five of 12 examined subjects in the affected group (42%), the number was less than in this control subject. The total number of Purkinje cells was less in all individuals with autism than the average number in the control group. The numerical density of Purkinje cells was also significantly less (p < 0.0024) in affected subjects (488/mm3) than in control subjects (645/mm3) (−24.4%).The average total number of Purkinje cells within the examined cerebellar hemispheres was significantly less (3) in the cohort with autism suggests that the detected neuronal deficits do not decrease greatly, if at all, from 4 to 60 years of age among subjects diagnosed with autism. However, examination of only three subjects with autism 52 to 60 years of age and of three control subjects 51–64 years of age is not favorable for detection of aging-associated neuronal loss.The absence of a significant correlation between age and the total number or numerical density of neurons  than in control subjects . The total number of Purkinje cells in the entire cerebellum of control subjects in our cohort 4–64 years of age is comparable to estimates reported by other authors, with some modifications due to age and methods: 28.5 million in 10 control males, 28–84 years of age ; 28.6 miAutism is associated with significant inter-individual differences in the number of Purkinje cells, but a smaller number of Purkinje cells was observed in the majority of 29 individuals diagnosed with autism . Recent3 and 31,133 mm3, respectively) was not significant. This volume reflects a 45% reduction of brain weight during dehydration in ethyl alcohol of the brains of control subjects and a 47% reduction in individuals diagnosed with autism. The volume calculated for both cerebellar hemispheres of control subjects and corrected for 45% shrinkage is equal to 113.2 mm3 and is comparable to 124.8 cm3 in the study by Andersen et al. [In the examined cohort, the difference between volumes of the cerebellar hemisphere in the group with autism and control groups . Several MRI studies of patients with autism have revealed increased volumes of the basal ganglia [The volume of the caudate nucleus was significantly greater in the group with autism than in the control group  appears to be another deregulated component of striatal circuits that may enforce repetitive behaviors in autism.A subcomponent of changes in the striatum is the significant deficit in the volume of neuronal soma in the nucleus accumbens (34%) and caudate nucleus (22%) in 4- to 8-year-old subjects with autism, but not in affected adolescents or adults . These dThe striatum alterations observed in idiopathic autism resemble some structural and functional changes observed in fragile X syndrome (FXS). Autism is diagnosed in 25–30% of individuals diagnosed with FXS -84. Hattp < 0.05) and 12% fewer neurons in the entire amygdala . The significantly (p < 0.017) reduced numerical density of neurons in the lateral nucleus in the amygdala of subjects with autism in our cohort of 14 subjects 4–60 years of age  and the absence of significant changes in other amygdala subdivisions in these subjects confirm the selective developmental abnormality of the lateral nucleus. In our study, the total number of neurons in the lateral nucleus in subjects with autism was also less (by 17%)  than in the control group , but after control for five covariates, the difference was found to be not significant. Differences in tissue preservation, the age of examined subjects, and selection of only epilepsy-free males in the study by Schumann and Amaral [Neuropathological studies  and resud Amaral  may contReduced neuronal density in the absence of a change in the total number of neurons in the amygdala may suggest the involvement of non-neuronal factors, including glia. Ahlsen et al.  reportedIndividuals with autism display deficits of social behavior, including abnormalities in social reciprocity, difficulties in the use of eye contact, and deficits in social motivation . The theStoner et al. study  revealedOur study of the archicortex of subjects with autism revealed focal microdysgenesis with selective deficits of stellate neurons in irregular smaller islands in the second layer of the entorhinal cortex in 23- and 60-year-old affected subjects . The redFor much of the history of postmortem studies of ASD pathology, brain abnormalities have been viewed as static , but theThe Fatemi et al.  review dComparison of the total number of neurons in the Ammons horn in this control group and control groups in other reports reveals differences related to the methods of tissue preservation and morphometric evaluation, and the age of examined cohorts. Our study revealed that the total numbers of neurons in the CA1, CA2/3, and CA4 sectors of control subjects 4–64 years of age were 11.5, 2.1, and 1.1 million, respectively. The numbers of neurons in the CA1, CA2/3, and CA4 sectors in control subjects 21–56 years of age were determined to be 14.7, 2.7, and 2.12 million, respectively ; for 47–Several studies have revealed neuronal pathology affecting cytoplasmic organelles and possibly sustaining functional abnormalities in autism, but there is no direct evidence that they cause significant neuronal death. An abnormal electron transfer chain in neuronal mitochondria may alter energy generation, metabolism, and cell structure and function; however, these changes prevail only in children, not in adults ,111. An The alterations in regional volume and neuron number in only a few brain structures in the autism cohort we studied here contrast with the brain region–specific developmental deficits in the volumes of neuronal soma detected in almost all examined brain regions as shown in our previous report . This diThis study increases the coherence of comparative stereological characteristics by the assessment of 38 brain structures and cytoarchitectonic subdivisions in a relatively large cohort of subjects diagnosed with autism using one standard of tissue preservation, embedding, sectioning, and staining and unbiased stereological estimates. The consistency of the characteristics of this cohort is enhanced by our previous analysis of qualitative developmental abnormalities , the stuThis postmortem study has been performed using anonymous coded brain tissue samples. Selected clinical records were extracted from the anonymous coded Autism Tissue Program - Autism Speaks database by authorized project PI.


In that case, barrel rolling should never occur, whether at the acute or chronic stage on firm ground or in water. Moreover, circling should have the same characteristics following both types of lesions. Clearly, 6-OHDA and APO-rats never exhibited barrel rolling at the acute stage. They circled at the acute stage of the lesion and continued to do so three weeks later, including in water. In contrast, UL-rats, exhibited both circling and barrel rolling at the acute stage, and then only circled on the ground. Furthermore, barrel rolling instantaneously reappeared in water in UL rats, which was not the case in 6-OHDA and APO-rats. That is, the lesion of the dopaminergic system on one side did not compromise trim in the pitch and roll planes, even when proprioceptive information related to the basis of support was lacking as in water. Altogether, these results strongly suggest that dopamine does not exert three-dimensional control of the motor system but regulates postural control in one particular plane of space, the one related to the basis of support. In contrast, as previously shown, the vestibular system exerts three-dimensional control on posture. That is, we show here for the first time a relationship between a given neuromodulator and the spatial organization of motor control.At the acute stage following unilateral labyrinthectomy (UL), rats, mice or guinea pigs exhibit a complex motor syndrome combining circling (HSCC lesion) and rolling (utricular lesion). At the chronic stage, they only display circling, because proprioceptive information related to the plane of support substitutes the missing utricular information to control posture in the frontal plane. Circling is also observed following unilateral lesion of the mesencephalic dopaminergic neurons by 6- hydroxydopamine hydrobromide (6-OHDA rats) and systemic injection of apomorphine (APO rats). The resemblance of behavior induced by unilateral vestibular and dopaminergic lesions at the chronic stage can be interpreted in two ways. One hypothesis is that the dopaminergic system exerts three-dimensional control over motricity, as the vestibular system does. If this hypothesis is correct, then a unilateral lesion of the nigro-striatal pathway should induce three-dimensional motor deficits, i.e., circling and at least some sort of barrel rolling at the acute stage of the lesion. Then, compensation could also take place very rapidly based on proprioception, which would explain the prevalence of circling. In addition, barrel rolling should reappear when the rodent is placed in water, as it occurs in UL vertebrates. Alternatively, the dopaminergic network, together with neurons processing the horizontal canal information, could control the homeostasis of posture and locomotion specifically in one and only one plane of space,  The vestibular system exerts a tridimensional control on posture and movement ,2: the hInterestingly, unilateral dopaminergic lesion also induces a rotation of the head about the axis of the cervical column towards the lesion side and a circling behavior –7. As eai.e. the plane related to the basis of support. In that case, barrel rolling should never occur, whether at the acute or chronic stage on firm ground or in water. Moreover, circling should have the same characteristics following both types of lesions. This paper is an attempt to address these questions by comparing quantitatively in three dimensions, the motor behavior of rats following unilateral vestibular and dopaminergic lesions both on the ground and in water.The resemblance between the consequences of a unilateral vestibular and dopaminergic lesion on motor behavior can be interpreted in two ways. One hypothesis is that the dopaminergic system exerts three-dimensional control over motricity, as the vestibular system does. If this hypothesis is correct, then a unilateral lesion of the nigro-striatal pathway should induce three-dimensional motor deficits, i.e., circling and at least some sort of barrel rolling at the acute stage of the lesion. Then, compensation of the postural syndrome in the frontal plane could also take place very rapidly, as in UL rats due to limbs proprioceptive information related to ground support, which would explain the prevalence of circling. In addition, barrel rolling should reappear when the rodents with unilateral dopaminergic lesions are placed in water due to the disappearance of proprioception. Alternatively, the dopaminergic network, together with neurons processing the horizontal canal information, could control the homeostasis of posture and locomotion specifically in one and only one plane of space, ad libitum. Data were collected from four wild type rats used as controls, eight rats with (left or right) unilateral lesions in the Substantia Nigra pars compacta, and five hemi-labyrinthectomized rats (left side).The animals used in this study were 8-week-old male Wistar rats . They were housed in groups of three per cage in a room with constant temperature (22°C), under 12:12 light- dark cycle, and with food pellets and water All surgeries were performed in deeply anesthetized rats . All studies were carried out in accordance with European Community Council directive of November 24th, 1986, and following the procedures issued by French Ministère de l’Agriculture. All efforts were made to minimize animal suffering and to reduce the number of animals used. All experiments were performed in Animal Research Facility under the approval ID B-75-1015 delivered by "Direction des Services Vétérinaires de la Préfecture de Paris" (France) and approved by a review board of Université Paris Descartes.substantia nigra (SN) for half of the rats and at the right A9 region for the other half. The coordinates were A 4.4, L 0.9, and V 7.2 for rats weighing 150–200 g and A 4.8, L 1.5, and V 7.5 for rats weighing 200–250 g [Fig 1). Apomorphine hydrochloride was dissolved in a solution of 0.9% saline and 0.1% ascorbic acid and was injected sub-cutaneously under the nape of the neck. In each case, the injection volume was 1 ml/kg; solutions of drugs were prepared fresh daily. Out of a total of 8 lesioned rats in the substantia nigra, only 3 were selected for the analyses after histological verification.Thirty minutes prior to surgery, the rats received an injection of desmethylimipramine (15 mg/kg ip) to protect noradrenergic neurons from the neurotoxic effects of 6- hydroxydopamine hydrobromide . Under sodium pentobarbital (Somnotol) anesthesia (25 mg/kg), they were positioned in a Kopf stereotoxic instrument and received an infusion of 6-OHDA  at a rate of 1 iA/mm through a 26-ga. stainless steel cannula . The cannula was left in place for a further 3 min to allow for passive diffusion away from the tip. Doses of 6-OHDA are expressed as the weight of the base. The cannula was aimed at the left A9 region of the 00–250 g . The lesIn brief, a global inner ear lesion was performed with the aid of an operating microscope. A retroauricular approach was used. The entire length of the ventral edge of the meatus was destroyed and the facial nerve sectioned. The tympanic membrane, malleus and incus were removed to expose the pterygopalatine artery caudal to the stapes. This artery was coagulated using an electro-coagulator, the stapes removed and the oval window opened. Finally, the vestibule was destroyed using a suction tube. A post-operative i.m. Terramycin  injection was given (50 mg tetracycline) to prevent infection, and the animals were then left free in normal visual conditions until compensation of the vestibular deficits . Out of To follow the movement in three-dimensional space, five digital cameras were used to register sequences of 8 seconds at 200 frames per second. Each of them was placed in specific planes of space so that at least two cameras would be able to capture and follow the same point in movement simultaneously.Prosilica GE680) at 200 frames/second . This first step was done to follow the locomotor behavior on the ground. Secondly, each animal was put in a transparent glass pool (80 x 40 x 40 cm) filled with 32 C° water to a height of 25 cm . The rats were delicately positioned at the surface of the water in the center of the tank and filmed at 200 frames/sec with the all five video cameras . Each exercise was done before and after (two minutes after) subcutaneous injection of Apomorphine (APO).The frequency was selected as a compromise between maximum time resolution and the spatial definition required for a frame-by-frame data analysis. The referenced animal was then first set on a small wood platform 30 x 30 cm, and filmed with three cameras ; 3 on the head  to obtain a three- dimensional reference point, 4 on the back , 1 on each shoulder and at the level of each femoro-pelvic junction to complete position of spine, and finally 1 on each foot, to identify the foot movement.To follow the changes of the skeletal geometry of the individual in the different conditions, fifteen small colored spherical markers (diameter of 5mm) were stuck on the skin of each animal ((Loco 3.01), and it was used for the 2D tracking of markers in every camera view. Using geometrical camera calibration from an object with known dimension and standard stereoscopic triangulation, the software allows the determination of the 3D Cartesian coordinates of the tracked markers along a sequence. These 3D trajectories were used to calculate various angles describing the skeletal geometry of the animal during locomotor behaviors (circling and pivoting). In addition, 3D anatomical models of the head and skeleton have been aligned with respect to the 3D trajectories of markers. These 3D anatomical models have been collected using an accurate microCT X-ray scanner (50 microns accuracy). This anatomical model permitted identification of the position of the different anatomical markers fixed on the skin of the animal . The 3D anatomical models include a segmentation of the vestibular system, allowing an estimation of the trajectory of the pitch angle of the HSCC . The head markers allowed us to calculate the pitch, the yaw and the roll of the head. To estimate the pitch angle (PitchH), we calculated the mean angle from the difference of pitch angle between the Marker 1 and 2 and pitch angle of the Marker 1 and 3 . The roll angle (RollH) was calculated between Marker 2 and 3 , and lastly the yaw angle (YawH) between segment delimited by Marker 1 and the theoretical midpoint between Marker 2–3 and the segment delimited by this same midpoint marker and the marker stuck between scapulas. Supplemental angles were measured along the spine axis, the yaw angle between the cervical and thoracic column (YawC1) and the yaw angle between the thoracic and lumbar column (YawC2). A cumulative value from the two previous yaw gave the yaw of the column .The roll angle (tilt) at the shoulder girdle level and the roll angle (tilt) at the pelvic girdle level were also quantified. Statistical comparisons were conducted using one-way ANOVA, and groups were then compared by means of the Bonferroni’s post-hoc test. The vectors, the angles analyzed and the statistics were computed using R [Statistica 6.1 , and Prism3.02 .The average velocity of body rotation was determined for each episode and the mean value was then calculated. Quantitative data acquisition was performed off-line using custom software  using R , StatistTable 1), then neither description of the locomotion, nor measures on the trajectories of the individual were done in these situations. However the YawH and RollH were estimated from straight ahead locomotion on a horizontal surface  (Table 2), while the PitchH (28°±6) could be measured from video-radiographies of previous studies on WT rat in movements.The control animals (WT) placed on the platform walked along the edges and tried to get out . The hindlimb ipsilateral to the lesion was never fully lifted off, but several repositionings at the center of the circular trajectory occurred . The others limbs showed alternating movements, with footfalls inside the trajectory of the head. The equivalent diameters of the circles were smaller than the diameter of the platform, and the rotation speed was 9 cm/s (Table 1). The position of the head was slightly different of the WT, the head being in a more horizontal position, the PitchH was less pronounced, the YawH was oriented toward the sense of the rotation, as the tilt (RollH) of the head (Table 2). The vertebral column was more curved than WT (YawC = 57°±1), with a difference of the YawC2, while the YawC1 did not change (Table 2).Following unilateral destruction of the dopaminergic neurons, the 6-OHDA-rats placed on the platform exhibited a circling behavior ipsiversive to the lesion . The hindlimb ipsilateral to the lesion was not active, and rotated without having left from the ground, while the hindlimb contralateral to the lesion performed backward steps, and forelimbs acted forwardly and laterally. The footfalls of HLc, FLc, FLi, were as in 6-OHDA inside the trajectory of the head . The diameter of the circle was not significantly smaller than 6-OHDA , however the number of circles per minute and the rotation speed were greatly increased 47 cm/s (Table 2). The PitchH of the APO-rats found again the WT value, while the YawH orientation was nearby to WT but still different from WT and OH. The tilt of the head was higher than previous in WT and 6-OHDA (Table 2). The lateral bending of the vertebral column was higher than WT and 6-OHDA (80°±15), with, as in previous, a significant difference of the YawC2, while the YawC1 did not change (Table 2).After apomorphine injection, the APO-rats placed on the platform exhibited pivoting behavior contraversive to the lesion . The diameters of the circles were not different to those of other rats; the rotation speed was slower than APO-rat but not different than the other rats (Table 1). However, at rest, they presented a static postural syndrome oriented toward the side of the lesion. This syndrome had two components: a rotation about the axis of the thoracic column caused a lateral tilt of the head-neck ensemble. This head tilt (RollH = 23° ± 14) was combined with a head rotation about the axis of the cervical column (YawH = 152° ± 6); the utricular macula lesion (UT) caused the head tilt, while the horizontal semicircular canal lesion (HSCC) caused its rotation. At last, the curvature of the vertebral column seemed to not be modified in comparison with injured rats, but less stable (highest SD = 52 for YawC).The unilateral labyrinthectomized rats (UL) as we previously described , presentIn summary, on ground, UL-rats displayed a 3D motor syndrome which concerned their mobility both in a plane related to their basis of support (circling) and to the roll and pitch plane. In contrast, 6-OHDA and APO- rats exhibited a 1D motor syndrome (circling and pivoting) only related to their mobility in a plane related to the support, and the impossibility to move straight-ahead.Fig 3D). The fore limbs were always extended and maintained ahead at the surface, while the hind limbs presented alternate movement as occurs in symmetrical walk. The diameter of the trajectory was compared to the diameter of the pool. The rats, to breathe, maintained their heads above the surface and then modified the PitchH (12° ± 2) compared to when over ground (Table 2). Additionally, as they swam close to the edge, they needed to turn at the corner of the pool, and then modified the different yaw angles (high SD for YawC2-C).When they were placed in the water, the control rats swam close to the edge of the rectangular pool . However, the motor behaviour of 6-OHDA rats was not markedly different from the control. When they swam, as was seen in WT, the hind limbs presented alternate movement as occurs in symmetrical walk, while the fore limbs were always extended and maintained ahead at the surface. The hindlimb contralateral to the lesion showed larger lateral movements than the hindlimb ipsilateral to the lesion . It was this difference of movement which caused the circling behaviour in the water. The 6-OHDA, like WT, maintained their head stable above the surface with the same PitchH and YawH, while the RollH was different to the WT (8° ± 5). The curvature of the vertebral column and the Roll plane of the girdles were not different from WT (Table 2).The 6-OHDA placed in the pool, circled toward the lesion side  about an axis located at the level of the hind limb contralateral to the lesion. APO-rats swam faster in tighter circles (Table 1). Contrary to control and 6-OHDA, they swam using the hind and forelimbs (S1 Movie), but the coordination of the limbs did not change and was still alternated. A new lateral component was added in the movement of the limbs, with highest amplitude of the limb ipsilateral to the lesion, which induced the pivoting of the APO rats . The orientation of the head, YawH, PitchH and RollH did not differ from 6-OHDA (C) was higher than in 6-OHDA. The lateral component added by the limb to induce the rotating behavior was concomitant with the change of the roll plane. This movement of the limbs did not change the roll angle of the both girdles, (Table 1).Following apomorphine injection, the sense of rotation reversed , which obliged one to rapidly rescue them. The Yaw, Pitch and Roll angles seem to not be different from the other rats, but the lack of an observed statistical difference could be because these values had the highest variability (Table 2).The UL-rats were tested in water three weeks after the lesion, once the circling and the postural deficits observed on ground had recovered. When gently placed in water, UL-rats immediately rolled again about their longitudinal axis toward the side of the lesion and swam away from the surface in random directions , and the extremity of the left fore limb, shows that the head is maintained in a horizontal plane and describes a circular trajectory, and the fore limb moves laterally, with alternate movement. 3D anatomical models of head and skeleton have been aligned with respect to the 3D trajectories of markers. These 3D anatomical models have been collected using an accurate micro-CT X-Ray scanner (50 microns accuracy). The 3D anatomical models include a segmentation of the vestibular system, allowing an estimation of the trajectory of the pitch angle of the HSCC.(AVI)Click here for additional data file.