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IntroductionIncreased plasma concentrations of proinflammatory cytokines are found in chronic schizophrenia patients, patients with first episode and in individuals with high risk for psychosis. The most replicated findings are increased concentrations of IL-6, TNF-α and IL-1β through different phases of the disorder while the results for two important proinflammatory cytokines IL8 and IFN-γ were not consistent.ObjectivesPrimary objective of this study was to assess differences in concentrations of IL-8, IFN-γ and IL-1β between schizophrenia patients and healthy controls, Secondary objective was to explore differences in first episode drug naïve patients.MethodsWe measured plasma concentrations of IL-8, IFN-γ and IL-1β in 64 healthy controls and 64 schizophrenia patients during acute exacerbation and remission phase. 25% were drug naive first episode schizophrenia patients. The patients were matched by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.ResultsLevels of IL-8 were significantly lower in patients with schizophrenia in acute phase and remission compared to healthy controls (p=0,009 for acute phase and p=0,020 for remission). There was no significant difference in the levels of INF-γ and IL-β between schizophrenia in acute phase and remission and healthy controls (p>0,05). In schizophrenia patients there was no difference in the levels of INF-γ, IL-β and IL-8 between acute phase, remission and healthy controls (p>0,05). There was no difference in plasma levels of IL-8, IFN-γ and IL-1β between first episode drug naïve and previously treated schizophrenia patients.ConclusionsOur research did not find disturbance of plasma levels of IFN-γ and IL-1β in schizophrenia patients, although the increase of IL-1β was the most replicated finding up to date. Interestingly and contrary to expected the finding of significantly decreased levels of IL-8 in schizophrenia patients requires further research since IL-8 plays a vital role in the inflammatory pathway and may be implicated in cognitive dysfunction.Disclosure of InterestNone Declared

Introduction The kynurenine pathway of tryptophan catabolism has come into the spotlight of schizophrenia research since its catabolites exert neuroactive effects. A strong body of evidence suggests that kynurenic acid, a catabolite of kynurenine pathway, acts as the only endogenous NMDA receptor antagonist leading to the weakening of circuits in layer III of dorsolateral prefrontal cortex of schizophrenia patients. Studies exploring the levels of kynurenic acid and other metabolites of tryptophan in peripheral blood did not yield any definite conclusions. Objectives Primary objective of this study was to assess differences in concentrations of key constituents of kynurenic pathway in blood plasma – tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) between schizophrenia patients (SCZ) and healthy controls (HC). Secondary objective was to explore correlations between these concentrations and clinical characteristics. Methods In our two-centre prospective case-control study we measured plasma concentrations of TRP, KYN and KYNA in 36 healthy controls (HC) and 38 schizophrenia (SCZ) patients during acute exacerbation and remission and explored the correlations with clinical parameters using PANSS scale. The patients were matched with HC by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances. Results TRP concentrations were significantly higher in HC than in SCZ patients in acute phase (p<0,001) and remission (p<0,001), while SCZ patients in acute phase had significantly higher TRP levels than in remission (p<0,01). Levels of KYNA and KYN were significantly lower in SCZ patients than in HC both in acute phase and remission, all with high statistical significance (p<0,001). There was no statistically significant difference between acute phase and remission neither for KYN (p>0,05), nor for KYNA (p>0,05). There was no correlation of plasma levels of TRP, KYN and KYNA with total PANSS score, PANSS positive scale score, PANSS negative scale score and PANSS general psychopathology scores, both in acute phase and remission (p>0,05). Also, there was no correlation between plasma levels of TRP, KYN and KYNA in SCZ patients in remission with improvements measured with PANSS scale (p>0,05). Conclusions Although there are concerns about the value of measurement of metabolites of kynurenine pathway in the peripheral blood, our data suggest that significantly decreased levels of KYN and KYNA could suggest that disrupted TRP degradation in SCZ patients may be reflected in the peripheral blood as well. Further studies of peripheral levels of kynurenine pathway metabolites on larger samples should also explore effects of antipsychotic therapy, but also their correlation with other clinical parameters such as neurocognition. Disclosure of Interest None Declared

DNA double strand breaks (DSBs) are the most common form of DNA damage and are repaired by non-homologous-end-joining (NHEJ) or homologous recombination (HR). Several protein components function in NHEJ, and of these, DNA Ligase IV is essential for performing the final ‘end-joining’ step. Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, increased predisposition to leukaemia and variable degrees of immunodeficiency. In this manuscript, we report the creation of a human induced pluripotent stem cell (iPSC) model of LIG4 deficiency, which accurately replicates the DSB repair phenotype of LIG4 patients. Our findings demonstrate that impairment of NHEJ-mediated-DSB repair in human iPSC results in accumulation of DSBs and enhanced apoptosis, thus providing new insights into likely mechanisms used by pluripotent stem cells to maintain their genomic integrity. Defects in NHEJ-mediated-DSB repair also led to a significant decrease in reprogramming efficiency of human cells and accumulation of chromosomal abnormalities, suggesting a key role for NHEJ in somatic cell reprogramming and providing insights for future cell based therapies for applications of LIG4-iPSCs. Although haematopoietic specification of LIG4-iPSC is not affected per se , the emerging haematopoietic progenitors show a high accumulation of DSBs and enhanced apoptosis, resulting in reduced numbers of mature haematopoietic cells. Together our findings provide new insights into the role of NHEJ-mediated-DSB repair in the survival and differentiation of progenitor cells, which likely underlies the developmental abnormalities observed in many DNA damage disorders. In addition, our findings are important for understanding how genomic instability arises in pluripotent stem cells and for defining appropriate culture conditions that restrict DNA damage and result in ex vivo expansion of stem cells with intact genomes.

Molecular machines, and in particular molecular motors with synthetic molecular structures and fuelled by external light, voltage or chemical conversions, have recently been reported 1 , 2 , 3 , 4 , 5 , 6 . Most of these experiments are carried out in solution with a large ensemble of molecules and without access to one molecule at a time, a key point for future use of single molecular machines with an atomic scale precision. Therefore, to experiment on a single molecule-machine, this molecule has to be adsorbed on a surface, imaged and manipulated with the tip of a scanning tunnelling microscope (STM) 7 , 8 , 9 , 10 . A few experiments of this type have described molecular mechanisms in which a rotational movement of a single molecule is involved. However, until now, only uncontrolled rotations 11 , 12 , 13 or indirect signatures 14 , 15 of a rotation have been reported. In this work, we present a molecular rack-and-pinion device for which an STM tip drives a single pinion molecule at low temperature. The pinion is a 1.8-nm-diameter molecule functioning as a six-toothed wheel interlocked at the edge of a self-assembled molecular island acting as a rack. We monitor the rotation of the pinion molecule tooth by tooth along the rack by a chemical tag attached to one of its cogs.

The effect of aloe emodin (AE), a herbal anthraquinone derivative, on the rat C6 glioma cell line was investigated. In addition to cell cycle block and caspasedependent apoptosis, AE led to the formation of intracytoplasmic acidic vesicles indicative for autophagic cell death. Moreover, differentiation of surviving cells toward the astrocytic lineage was confirmed by typical morphological changes and increased expression of glial fibrillary acidic protein (GFAP). AE did not affect the activation of mitogen-activated protein kinase p38, Jun-N-terminal kinase, or transcription factor NF-κB, but markedly inhibited the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in C6 cells. A selective inhibitor of ERK activation, PD98059, mimicked the effects of AE on glioma cell morphology and GFAP expression, but failed to induce either apoptosis or autophagy. Taken together, these results indicate that the anti-glioma action of AE involves ERK-independent induction of both apoptosis and autophagy, as well as ERK inhibition-mediated differentiation of glioma cells.

BackgroundAlveolar echinococcosis (AE) is a neglected zoonosis presenting with focal liver lesions (FLL) with a wide range of imaging patterns resembling benign as well as malignant FLLs. Complementary serology and histopathology may be misleading.ObjectiveThe objective of our study is to highlight pitfalls leading to wrong diagnoses and harmful interventions in patients with AE.DesignThis retrospective sentinel case series analyses diagnostic and treatment data of patients with confirmed AE.Results80 patients treated between 1999 and 2014 were included in the study. In 26/80 patients treatment decisions were based on a wrong diagnosis. AE was mistaken for cystic echinococcosis (CE) in 12/26 patients followed by cholangiocellular carcinoma (CCA) in 5/26 patients; 61/80 patients had predominantly infiltrative liver lesions and 19/80 patients had a predominantly pseudocystic radiological presentation. Serology correctly differentiated between Echinococcus multilocularis and Echinococcus granulosus in 53/80 patients. Histopathology reports attributed the right Echinococcus species in 25/58 patients but failed to differentiate E. multilocularis from E. granulosus in 25/58 patients. Although contraindicated in AE 8/25 patients treated surgically had instillation of a protoscolicidal agent intraoperatively. One of the eight patients developed toxic cholangitis and liver failure and died 1 year after liver transplantation.ConclusionsMisclassification of AE leads to a critical delay in growth inhibiting benzimidazole treatment, surgical overtreatment and bares the risk of liver failure if protoscolicidal agents are instilled in AE pseudocysts.

The paper presents the results of a technical and economic analysis of three stand-alone hybrid power systems based on renewable energy sources which supply a specific group of low-power consumers. This particular case includes measuring sensors and obstacle lights on a meteorological mast for wind measurements requiring an uninterrupted power supply in cold climate conditions. Although these low-power (100 W) measuring sensors and obstacle lights use little energy, their energy consumption is not the same as the available solar energy obtained on a daily or seasonal basis. In the paper, complementarity of renewable energy sources was analysed, as well as one of short-term lead-acid battery-based storage and seasonal, hydrogen-based (electrolyser, H2 tank, and fuel cells) storage. These relatively complex power systems were proposed earlier for high-power consumers only, while this study specifically highlights the role of the hydrogen system for supplying low-power consumers. The analysis employed a numerical simulation method using the HOMER software tool. The results of the analysis suggest that solar and wind-solar systems, which involve meteorological conditions as referred to in this paper, include a relatively large number of lead-acid batteries. Additionally, the analysis suggests that the use of hydrogen power systems for supplying low power-consumers is entirely justifiable, as it significantly reduces the number of batteries (two at minimum in this particular case). It was shown that the increase in costs induced by the hydrogen system is acceptable. nema

The most common lacrimal sac pathology is chronic inflammation with or without occlusive fibrosis. However, a substantial number of lacrimal sac-specific pathologies were reported throughout the literature which may mimic chronic inflammation and be misdiagnosed. From a tertiary ophthalmic care centre in Serbia, in a single ophthalmic pathology laboratory, during a 7-year period (January 2004 to October 2010), a 599 consecutive lacrimal sac wall biopsy samples routinely obtained during external dacryocystorhinostomy in adult patients with clinically presumed primary acquired lacrimal drainage system obstruction were analysed. Although non-specific lacrimal sac pathology was present in the vast majority of cases (578 biopsy specimens; 96.49%), this report also reveals a relatively substantial number (21 biopsy specimens; 3.51%) of clinically non-suspected or intraoperatively unexpected primary lacrimal sac-specific pathology—among them, six lesions with malignant biological behaviour were identified: one microinvasive squamous cell carcinoma and five malignant lymhoproliferative lesions. Usefulness of routine lacrimal sac wall biopsy during surgery for primary acquired lacrimal drainage system obstruction is undoubtful and commensurate with the constant need for better understanding of the pathological processes that involve lacrimal drainage system.

Putting to work a molecule able to collect and carry adatoms in a controlled way on a surface is a solution for fabricating atomic structures atom by atom. Investigations have shown that the interaction of an organic molecule with the surface of a metal can induce surface reconstruction down to the atomic scale 1 , 2 , 3 , 4 , 5 . In this way, well-defined nanostructures such as chains of adatoms 2 , atomic trenches 3 , 4 and metal–ligand compounds 5 have been formed. Moreover, the progress in manipulation techniques 6 , 7 , 8 , 9 , 10 induced by a scanning tunnelling microscope (STM) has opened up the possibility of studying artificially built molecular-metal atomic scale structures 11 , 12 , and allowed the atom-by-atom doping of a single C 60 molecule by picking up K atoms 13 . The present work goes a step further and combines STM manipulation techniques with the ability of a molecule to assemble an atomic nanostructure. We present a well-designed six-leg single hexa- t -butyl-hexaphenylbenzene (HB-HPB) molecule 14 , which collects and carries up to six copper adatoms on a Cu(111) surface when manipulated with a STM tip. The ‘HB-HPB-Cu atoms’ complex can be further manipulated, bringing its Cu freight to a predetermined position on the surface where the metal atoms can finally be released.

Purpose Hepatic alveolar echinococcosis (AE) resembles intrahepatic cholangiocarcinoma (ICC) on radiological imaging. The purpose of this study was to identify criteria to discriminate AE from ICC with CT and MR Imaging. Methods One hundred and sixteen imaging studies of 94 patients (CT n  = 65; MRI n  = 51) diagnosed with AE ( n  = 55) or ICC ( n  = 39) were retrospectively reviewed by two blinded radiologists for lesion features including enhancement pattern and matrix composition. A consensus read was conducted in cases of disagreement. Uni- and multivariate logistic regression with bootstrapping were used for analysis. Results Using CT, no or septal enhancement and calcification yielded the highest values of sensitivity/specificity (90.9%/90.6% and 81.8%/96.9%) for AE. Using MRI, no or septal enhancement and cystic components achieved the highest sensitivity/specificity (90.9%/100.0% and 84.8%/66.7%) for AE. Multivariate logistic regression identified the following strong independent predictors for AE: for MRI, no or septal enhancement (odds ratio [OR] 322.4; p  < 0.001); for CT, no or septal enhancement and calcification (OR 35.9 and 42.5; p  < 0.001 and p  < 0.01, respectively). No or septal enhancement and calcification demonstrated the highest interreader agreement (>90%). Conclusion Enhancement characteristics and matrix calcifications offer the strongest discriminating potential between AE and ICC with a high sensitivity, specificity, and interreader agreement.