Intraocular pressure before and after capsulorhexis using two viscoelastic substances and two surgical approaches in enucleated porcine eyes

AIM:To investigate the influence of ophthalmic viscoelastic devices(OVDs)and different surgical approaches on the intraocular pressure(IOP)before and after creation of the curvilinear circular capsulorhexis(CCC)as a measure for anterior chamber stability during this maneuver.METHODS:Prospective experimental WetLab study carried out on enucleated porcine eyes.IOP was measured before and after CCC with the iCare Rebound tonometer(iCare ic200;iCare Finland Oy,Vantaa,Finland).The OVDs used were a cohesive one[Z-Hyalin,Carl Zeiss Meditec AG,Germany;hyaluronic acid(HA)]and a dispersive[Z-Celcoat,Carl Zeiss Meditec AG,Germany;hydroxy propylmethylcellulosis(HPMC)].The CCC was created using Utrata forceps or 23 g microforceps in different combinations with the OVDs.RESULTS:Using the Utrata forceps the IOP dropped from 63.65±6.44 to 11.25±3.63 mm Hg during the CCC.The use of different OVDs made no difference.Using the 23 g microforceps the IOP dropped from 65.35±8.15 to 36.55±6.09 mm Hg.The difference between IOP drop using either Utrata forceps or 23 g microforceps was highly significant regardless of the OVD used.CONCLUSION:Using the sideport for the creation of the capsulorhexis leads to a lesser drop in IOP during this maneuver compared to the main incision in enucleated porcine eyes.The use of different OVD has no significant influence on IOP drop.

Brain network correlates of epilepsy occurrence in multiple sclerosis and neuroinflammation

Multiple sclerosis(MS),the most common inflammatory condition of the central nervous system in young adults,is characterized by immunemediated demyelination and neurodegeneration that translate into heterogeneous clinical phenotypes and disease trajectories.

Innovative immunohistochemistry identifies MMP-9 expressing macrophages at the invasive front of murine HCC

AIM:To investigate the proteolytic contribution of tumor-associated macrophages(TAM)in tumor invasion,we analyzed whether TAM at the invasive front of small HCC in Abcb4-/--mice show an enhanced expression of MMP-9. METHODS:Liver cryosections of the hepatocellular carcinoma(HCC)invasive front from 12 mo old Abcb4-/--mice were stained for collagen typeⅠand MMP-9 using Alexa488 and Alexa568 labeled secondary antibodies.Afterwards,the Alexa568 dye was bleached and the macrophage marker F4/80 was visualized using Alexa568 labeled secondary antibodies.Finally, photographs of the invasive tumor front were digitally overlaid and analyzed. RESULTS:After complete bleaching of the primary dye,specific fluorescence staining of a third antigen, here F4/80,was successfully performed on the same histological section.With this method,we were able to identify conglomerates of matrix metalloproteinase (MMP-9)expressing macrophages within the tumor capsule of HCC. CONCLUSION:MMP-9 expressing macrophages are involved in matrix remodelling at the invasive tumor front of HCC.The described staining protocol provides a simple yet powerful extension of conventional immuno-histochemistry,facilitating visualization of at least three different antigens plus nuclei in one single histological section.

Potential Correlations between Unexplained Experimental Observables and Hot Projectile-Like Fragments in Primary Interactions above <i>E</i>_CM/<i>u</i>≈ 150 MeV

An enhanced neutron production and an enhanced nuclear destruction due to secondary fragments have been observed in very thick targets irradiated with high energy ions. This enhancement is beyond theoretical calculations and it is an unresolved problem. It is observed only when primary ion interactions exceed an energy threshold (ECM/u ≈ 150 MeV). Investigations using nuclear emulsions for very high-energy nuclear reactions suggest that two distinctly different classes of relativistic projectile-like fragments are emitted in primary interactions: a “cool” channel with a temperature of (T(p)cool ≈ 10 MeV), and a “hot” channel with (T(p)hot ≈ 40 MeV. This second reaction class may induce the above mentioned enhanced reactions of secondary fragments, thus being responsible for unresolved problems. This assumption should be studied in further experiments. Nuclear interactions of secondary particles in thick targets are of interest, in particular in view of radiation protection needs for high energy and high intensity heavy ion accelerators. Many basic ideas of this paper go back to the late Professor E. Schopper (Frankfurt).

Cell-type specific and non-redundant anti-proliferative effects of shRNA-mediated Galpha12- and Galpha13 knockdown in lung cancer cell lines

In small cell lung cancer cells, various autocrine stimuli lead to the parallel activation of Gq/11 and G12/13 proteins. The contribution of the Gq/11-PLC-β cascade to the mitogenic effects in SCLC cells is well established, but the relevance of G12/13 signaling is less explored. While in prostate and breast cancer, G12/13 activation has been shown previously to promote invasiveness without being involved in cellular proliferation, previous data from our group indicate anti-proliferative effects of G12/13 knockdown in small cell lung cancer (SCLC) cells. To further investigate the role of G12/13-dependent signaling in lung tumor cells, we employed shRNA-mediated targeting of Gα12, Gα13, or both, in SCLC and NSCLC cell lines. Lentiviral expression of shRNAs resulted in specific Gα12 and Gα13 knockdown. Of note, upon single knockdown of one family member, no counter-upregulation of the other one was observed. Interestingly, inhibition of proliferation was cell line dependent. In cell lines where knock-down led to antiproliferation, single knockdown of either Gα12 or Gα13 was sufficient to impair proliferation and double knockdown of Gα12 and Gα13 tended not to further increase anti-proliferative effects. Likewise, when single knockdown was insufficient for an inhibition of proliferation, no effects were observed in double knockdowns. Taken together, these findings indicate that both Gα12 and Gα13 affect cellular proliferation individually and interference with one family member is sufficient for anti-tumor effects.

Clinical and pharmacological properties of new oral anticoagulants for the prevention of cerebral thromboembolism: Factor Xa and thrombin inhibitors

Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.

On the Perturbation Correction Factor <i>p_cav</i>of the Markus Parallel-Plate Ion Chamber in Clinical Electron Beams

Purpose: All present dosimetry protocols recommend well-guarded parallelplate ion chambers for electron dosimetry. For the guard-less Markus chamber, an energy dependent fluence perturbation correction pcav is given. This perturbation correction was experimentally determined by van der Plaetsen by comparison of the read-out of a Markus and a NACP chamber, which was assumed to be “perturbation-free”. Aim of the present study is a Monte Carlo based reiteration of this experiment. Methods: Detailed models of four parallel-plate chambers (Roos, Markus, NACP and Advanced Markus) were designed using the Monte Carlo code EGSnrc and placed in a water phantom. For all chambers, the dose to the active volume filled with low density water was calculated for 13 clinical electron spectra (E0 = 6 - 21 MeV) and three energies of an Electra linear accelerator at the depth of maximum and at the reference depth under reference conditions. In all cases, the chamber’s reference point was positioned at the depth of measurement. Moreover, the dose to water DW was calculated in a small water voxel positioned at the same depth. Results: The calculated dose ratio DNACP/DMarkus, which according to van der Plaetsen reflects the fluence perturbation correction of the Markus chamber, deviates less from unity than the values given by van der Plaetsen, but exhibits similar energy dependence. The same holds for the dose ratios of the other well-guarded chambers. But, in comparison to water, the Markus chamber reveals the smallest overall perturbation correction which is nearly energy independent at both investigated depths. Conclusion: The simulations principally confirm the energy dependence of the dose ratio DNACP/DMarkus as published by van der Plaetsen. But, as shown by our simulations of the ratio DW/DMarkus, the conclusion drawn in all dosimetry protocols is questionable: in contrast to all well-guarded chambers, the guard-less Markus chamber reveals the smallest overall perturbation correction and also the smallest energy dependence.

Effects of Electropulsing Induced Microstructural Changes on THz-Reflection and Electrical Conductivity of Al-Doped ZnO Thin-Films

Electropulsing induced phase transformation and crystal orientation change and their effects on electrical conductivity, THz reflection and surface roughness of thin-films of Al2O3 (2 wt%) doped ZnO were studied using XRD, SEM, AFM and Thz spectroscopy techniques. AZO-2 thin-films showed an effective response in THz spectroscopy under electropulsing. Electropulsing induced circular preferred crystal orientation changes and phase transformations were observed. The preferred crystal orientation changes accompanying decrease in stress and the secondary phase precipitation favored enhancing conductivity and THz reflection of the AZO-2 thin-films. After adequate electropulsing, both THz reflection and electrical conductivity of the thin-films were enhanced by 22.8% and 6.8%, respectively;meanwhile surface roughness reduced. The property responses of electropulsing are discussed from point view of microstructural change and dislocation dynamics.

Programmed cell death protein 4 expression in renal cell carcinoma, penile carcinoma and testicular germ cell cancer

AIM:To investigate the expression of programmed cell death 4(Pdcd4)tumor suppressor gene in tissue specimen of renal cell carcinoma(RCC),testicular germ cell cancer and penile cancer.METHODS:Pdcd4 expression was studied using immunohistochemistry in 188 cases of RCC and 28 controls(including 9 oncocytoma);in 74 cases of penile carcinoma(including 17 metastatic tissue samples)and26 controls;in 11 cases of seminoma,in 14 cases of non-seminoma and 5 controls.RESULTS:Control tissues exhibited strong core and cytoplasmatic Pdcd4 staining.In contrast,core and cy-toplasmatic Pdcd4 levels were significantly decreased in cancer tissues.CONCLUSION:Our data support a role for Pdcd4(down-)regulation in urologic tumors.Interestingly,Pdcd4 expression seem to be a potential diagnostic marker for renal or penile tumors.

达哌啶醇氟哌利多、多拉司琼单独或联合应用预防玻璃体切割术后的恶心和呕吐

Purpose Droperidol and the new serotonin -3antagonists are effective drugs for the prophyla xis of postoperative nausea and vomiting(PONV).The aim of this trial was to evaluate whether dolasetron coul d be a substitute for droperidol,because the Food and Dru g Administration has required a Black Box warning on th e droperidol package insert.Design Randomized,placebo-controlled,double-blinded trial.Participant s Inpatients undergoing vitreoretinal surgery(standard 3-port pars plana vitrecto-my for proliferative diabetic vitre oretinopathy,complicat-ed retinal detachment,or macular di sease,such as macular pucker,macular hole,or choroidal neovascu-larization).Intervention Two hundred forty patients(3×80)receiving droperidol(10μg·kg -1 ),dolasetron(12.5mg ),or the combination of both drugs adm inis-tered 5to 10minutes before the end of surgery.Control Eighty patients received saline pla cebos as controls.Methods Standardized general anesthesia was performed,including benzodiazepine premedic ation,propofol,a-tracurium or vecuronium,desfluran e in N 2 O /O 2 ,and a continuous infusion of remifentani l.Postoperative anal-gesia and antiemetic rescue medication were standard-ized.Episodes of vomiting,retchin g,nausea,and the need for additional antiemetics were recorded for 24hours.Main outcome measures Severity of PONV(rated by a standardized scoring algorithm)-was analyzed as the main end point of the study using the K ruskal-Wallis test.Results Data of 304patients could be analyzed.Mean severity scores in the placebo,dolasetron,droperidol,and combination groups were 1.21,0.76,0.47,and 0.30.Incidences of PONV of any severity were 56%,40%,28%,and 18%,respectively.The reduction of the incidence of PONV an d its severity was statistically significant in the dr operidol group and in the combination group relative to the pl acebo.Dolasetron alone failed to reduce the incidence of PONV.The combination of dolasetron and droperidol showed an ad-ditive antiemetic efficacy.Conclu sion Low-dose droperi-dol(10μg·kg -1 )but not dolasetron(12.5mg )re-duced postoperative nausea and vomi ting after vitreoreti-nal surgery.Dolasetron(12.5mg )is not an equivalent substitute for droperidol.

Perinatal testicular torsion—An emergency with grave consequences

Introduction: Perinatal testicular torsion is not a frequent, but a grave finding finding. As only immediate surgical retorsion may save the viability of the testicle, time is of essence. We report the case of a newborn where delayed diagnosis led to an unnecessary loss of one testicle. Presentation of Case: The newborn was presented one day after delivery with a swollen left blue scrotal pouch. The left testicle was little tender, higher in position and enlarged. Ultrasound revealed a globular, enlarged testicle left, showing hypodense necrotic areas within. Doppler sound could not detect any perfusion of the spermatic vessels. Scrotal fluid was present bilaterally. At operation, the testicle was considered unsalvageable, and left orchiectomy and right orchidopexy were performed. Discussion: In the new-born, it is more than convenient to perfom ultrasound of both testicles at the same time, which allows to compare texture and perfusion easily. Immediate surgical exploration should be performed at any time, even if in diagnostic doubt. The very most important step though is to professionally recognise and to react to this pediatric emergency, as time is of paramount essence. Conclusion: A case of a male newborn with unilateral perinatal testicular torsion is presented, where typical clinical signs and ultrasound features can be seen. Early exploration with orchiectomy of the necrotic testicle and orchidopexy of the healthy side may save the endocrine function and fertility.

Subfunctionalization of a monolignol to a phytoalexin glucosyltransferase is accompanied by substrate inhibition

Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the encoded enzymes often glycosylating multiple substrates and some exhibiting substrate inhibition kinetics,but the biological function and molecular basis of these phenomena are not fully understood.The promiscuous monolignol/phytoalexin glycosyltransferase NbUGT72AY1 exhibits substrate inhibition(Ki)at 4 mM scopoletin,whereas the highly homologous monolignol StUGT72AY2 is inhibited at 190 mM.We therefore used hydrogen/deuterium exchange mass spectrometry and structure-based mutational analyses of both proteins and introduced NbUGT72AY1 residues into StUGT72AY2 and vice versa to study promiscuity and substrate inhibition of UGTs.A single F87I and chimeric mutant of NbUGT72AY1 showed significantly reducedscopoletin substrate inhibition,whereas its monolignolgly cosylation activity was almost unaffected.Reverse mutations in StUGT72AY2 resulted in increased scopoletin glycosylation,leading to enhanced promiscuity,which was accompanied by substrate inhibition.Studies of 3D structures identified open and closed UGT conformers,allowing visualization of the dynamics of conformational changes that occur during catalysis.Previously postulated substrate access tunnels likely serve as drainage channels.The results suggest a two-site model in which the second substrate molecule binds near the catalytic site and blocks product release.Mutational studies showed that minor changes in amino acid sequence can enhance the promiscuity of the enzyme and add new capabilities such as substrate inhibition without affecting existing functions.The proposed subfunctionalization mechanism of expanded promiscuity may play a role in enzyme evolution and highlights the importance of promiscuous enzymes in providing new functions.

驱动堆中长寿命核废料碘的嬗变研究

利用理论模拟和实验手段对加速器驱动的快中子堆消除常规反应堆排放的核废料碘进行了研究 .实验中 ,利用加速器加速质子使其能量达到1 0GeV ,并轰击重金属铅靶 ,利用靶中产生的次级中子诱发核废料12 9I的嬗变 ,使其嬗变为稳定同位素130 Xe .对实验嬗变效率进行了理论模拟验证 ,进而拓宽到研究的驱动堆体系中 .堆芯区的核燃料为乏燃料铀和钚 。

Targeting metabolic rewiring might decrease spread of tumor cells: Mitochondrial tRNA modifications promote cancer metastasis

In a recent study published in Nature,Delaunay and colleagues demonstrate that tRNA modifications in mitochondria have the potential to affect the synthesis of mitochondrial proteins involved in oxidative phosphorylation(OXPHOS),which drives the invasive spread of cancer cells.The inhibition of one particular RNA-modifying enzyme was sufficient to prevent the cancer cell invasion and dissemination.

No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors

Background:IgG-class autoantibodies to N-Methyl-D-Aspartate(NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis.Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results.We measured NMDA antibodies in a large,well phenotyped sample of Parkinson patients without and with cognitive impairment(n=296)and controls(n=295)free of neuropsychiatric disease.Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.Methods:NMDA antibodies were analysed in the serum of patients and controls using well established validated assays.We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.Results:The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients(13%)than in controls(22%)and higher than in previous studies in both groups.NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment,nor with quantitative indicators of disease severity and cognitive impairment.A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.Conclusion:It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g.to Parkinson disease with dementia,while NMDA IgG antibodies define a separate disease of its own.

Seizure related injuries — Frequent injury patterns, hospitalization and therapeutic aspects

Purpose: Epileptic seizures frequently result in distinct physical injuries, fractures, traumatic brain injuries and minor trauma. The aim of this study was to retrospectively determine the frequent injury patterns due to seizure episode and to analyze consecutive acute medical care. Methods: This retrospective mono-center study was conducted at Frankfurt University Hospital, Frankfurt am Main, Germany between January 2007 and December 2017. Epilepsy patients with seizure-related fractures admitted to the emergency department were identified via a retrospective systematic query in the hospital information system using the ICD-10 German modification codes G40.0—G40.9. Patients with an unclear diagnosis of epilepsy were excluded. Sociodemographic as well as disease specific aspects were analyzed. Descriptive and Kruskal—Wallis one-way analysis of variance were used for statistical analysis. Results: A total number of 62 epilepsy patients were included. The mean age was 58.1 years. Fractures concerned the upper extremity most frequently (43.5%,n= 20), and 70.0% (14/20) were humerus fractures. Admission to intensive care unit for acute trauma care was necessary in 29.0% patients (n = 18), and surgery in 45.2% patients (n = 28). Twenty-five patients (26.6%) showed clinical or radiological signs of traumatic brain injury. Provoking factors were identified in 20 patients (32.3%), i.e., acute withdrawal or excess of alcohol (n = 15), relevant sleep deprivation (n = 2), and intoxication or withdrawal of other illegal drugs or trivial infect (n = 1 for each) and non-compliance with anti-seizure drugs (n = 1). A decreased T-score (-1.04 ± 1.15) and Z-score (-0.84 ± 0.75) compared to healthy subjects were found. Conclusion: Fractures in upper extremities, trunk and craniocerebral trauma occur frequently as seizure-induced injuries. Alcohol excess and withdrawal are important provoking factors and should be targeted with preventive measurements to avoid seizure related injuries and accidents.

Catchment soils as a factor of trace metal accumulation in sediments of the reservoir Klingenberg(eastern Ore Mountains, Germany)

The release and accumulation dynamics of trace metals in soils and aquatic sediments were exemplarily investigated in the catchment area of the Reservoir Klingenberg(Germany).Catchment soils were examined for mobilizable and total concentrations of arsenic(As),cadmium(Cd),chrome(Cr),iron(Fe),manganese(Mn),nickel(Ni),lead(Pb),and zinc(Zn)and compared with trace metal quantities accumulated in riverbed and reservoir sediments.The comparison of all samples showed relatively small variations of Cr(7.96–46.0 mg/kg),Fe(7.79–40.4 g/kg),and Ni(6.06–56.5 mg/kg),while stronger differences were found for As(11.2–164 mg/kg),Cd(0.14–30.5 mg/kg),Mn(0.08–1.84 g/kg),Pb(20.7–183 mg/kg),and Zn(69.1–916 mg/kg).The catchment soils were slightly enriched by Cd,Pb,and Zn.Especially Cd and Zn were characterized by large mobilizable proportions.The mean trace metal concentrations in riverbed sediments were higher than in catchment soils,while reservoir sediments accumulated the highest amounts of the analyzed elements.The enrichment of trace metals in reservoir sediments was generally determined by the sedimentation of fine particles,while the distribution of As,Fe,and Mn was additionally impacted by redox conditions.For Cd and Zn,which in comparison were most enriched in riverbed and reservoir sediments,a significant release from soils by leaching processes was observed.The accumulation of As and Pb in reservoir sediments was influenced to a greater extent by soil erosion and by anthropogenic or chalcogen sources in the catchment.