Prospective Evaluation of Kidney Function in Long-Term Survivors of Pediatric CNS Tumors.

Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens. Methods: Patients treated for a CNS tumor were prospectively evaluated up to 12 years after completion of their therapy. Examination of kidney function was performed during routine follow-up visits. Blood pressure and blood and urine parameters were analyzed for kidney function evaluation. Glomerular function was assessed by calculating the estimated glomerular filtration rate (eGFR), tubular functions were analyzed by measuring serum electrolytes, bicarbonate and phosphate reabsorption, and proteinuria was assessed by calculating the protein/creatinine ratio and phosphate reabsorption. Results: None of the 65 patients evaluated suffered from clinically relevant kidney impairment (eGFR < 90 mL/min/L, 73 m2). There was no association between chemotherapy dose and eGFR. Only two patients showed mild signs of tubulopathy and 11 patients were diagnosed with elevated blood pressure. Conclusion: With adequate supportive measures, such as sufficient hydration according to chemotherapy protocol guidelines, as well as avoidance or close monitoring of additional nephrotoxic medication, impaired kidney function is rare in CNS tumor survivors treated with standard chemotherapy. Nonetheless, long-term follow-up is essential for early detection of mild impairment of kidney function.

Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models.

Three dimensional (3D) bioprinting of multiple cell types within optimised extracellular matrices has the potential to more closely model the 3D environment of human physiology and disease than current alternatives. In this study, we used a multi-nozzle extrusion bioprinter to establish models of glioblastoma made up of cancer and stromal cells printed within matrices comprised of alginate modified with RGDS cell adhesion peptides, hyaluronic acid and collagen-1. Methods were developed using U87MG glioblastoma cells and MM6 monocyte/macrophages, whilst more disease relevant constructs contained glioblastoma stem cells (GSCs), co-printed with glioma associated stromal cells (GASCs) and microglia. Printing parameters were optimised to promote cell-cell interaction, avoiding the 'caging in' of cells due to overly dense cross-linking. Such printing had a negligible effect on cell viability, and cells retained robust metabolic activity and proliferation. Alginate gels allowed the rapid recovery of printed cell protein and RNA, and fluorescent reporters provided analysis of protein kinase activation at the single cell level within printed constructs. GSCs showed more resistance to chemotherapeutic drugs in 3D printed tumour constructs compared to 2D monolayer cultures, reflecting the clinical situation. In summary, a novel 3D bioprinting strategy is developed which allows control over the spatial organisation of tumour constructs for pre-clinical drug sensitivity testing and studies of the tumour microenvironment.

Fine-Tuning the Activation Mode of an 1,3-Indandione-Based Ruthenium(II)-Cymene Half-Sandwich Complex by Variation of Its Leaving Group.

Fine-tuning of the properties of a recently reported 1,3-indandione-based organoruthenium complex is attempted to optimize the stability under physiological conditions. Previous work has shown its capacity of inhibiting topoisomerase IIα; however, fast aquation leads to undesired reactions and ligand cleavage in the blood stream before the tumor tissue is reached. Exchange of the chlorido ligand for six different N-donor ligands resulted in new analogs that were stable at pH 7.4 and 8.5. Only a lowered pH level, as encountered in the extracellular space of the tumor tissue, was capable of aquating the complexes. The 50% inhibitory concentration (IC50) values in three human cancer cell lines differed only slightly, and their dependence on the utilized leaving group was smaller than what would be expected from their differences in cellular accumulation, but in accordance with the very minor variation revealed in measurements of the complexes' lipophilicity.

Ultraviolet light illuminates the avian nature of the Berlin Archaeopteryx skeleton.

The question of whether the iconic avialan Archaeopteryx was capable of active flapping flight or only passive gliding is still unresolved. This study contributes to this debate by reporting on two key aspects of this fossil that are visible under ultraviolet (UV) light. In contrast to previous studies, we show that most of the vertebral column of the Berlin Archaeopteryx possesses intraosseous pneumaticity, and that pneumatic structures also extend beyond the anterior thoracic vertebrae in other specimens of Archaeopteryx. With a minimum Pneumaticity Index (PI) of 0.39, Archaeopteryx had a much more lightweight skeleton than has been previously reported, comprising an air sac-driven respiratory system with the potential for a bird-like, high-performance metabolism. The neural spines of the 16th to 22nd presacral vertebrae in the Berlin Archaeopteryx are bridged by interspinal ossifications, and form a rigid notarium-like structure similar to the condition seen in modern birds. This reinforced vertebral column, combined with the extensive development of air sacs, suggests that Archaeopteryx was capable of flapping its wings for cursorial and/or aerial locomotion.

Detection of lost calamus challenges identity of isolated Archaeopteryx feather.

In 1862, a fossil feather from the Solnhofen quarries was described as the holotype of the iconic Archaeopteryx lithographica. The isolated feather's identification has been problematic, and the fossil was considered either a primary, secondary or, most recently, a primary covert. The specimen is surrounded by the 'mystery of the missing quill'. The calamus described in the original paper is unseen today, even under x-ray fluorescence and UV imaging, challenging its original existence. We answer this question using Laser-Stimulated Fluorescence (LSF) through the recovery of the geochemical halo from the original calamus matching the published description. Our study therefore shows that new techniques applied to well-studied iconic fossils can still provide valuable insights. The morphology of the complete feather excludes it as a primary, secondary or tail feather of Archaeopteryx. However, it could be a covert or a contour feather, especially since the latter are not well known in Archaeopteryx. The possibility remains that it stems from a different feathered dinosaur that lived in the Solnhofen Archipelago. The most recent analysis of the isolated feather considers it to be a primary covert. If this is the case, it lacks a distinct s-shaped centerline found in modern primary coverts that appears to be documented here for the first time.

Knoetschkesuchus langenbergensis gen. nov. sp. nov., a new atoposaurid crocodyliform from the Upper Jurassic Langenberg Quarry (Lower Saxony, northwestern Germany), and its relationships to Theriosuchus.

We report a new, small-sized atoposaurid crocodyliform from the Upper Jurassic of Langenberg, Northeastern Germany. Atoposaurids are small-sized Mesozoic crocodyliforms of mainly European distribution, which are considered to be phylogenetically close to the origin of Eusuchia. Knoetschkesuchus langenbergensis gen. nov. sp. nov. is represented by two well-preserved skulls and additional cranial and postcranial remains representing different ontogenetic stages. 3D reconstructions of a juvenile skull based on micro-computed tomography allow the most detailed description of cranial remains of any atoposaurid hitherto presented. Our new analysis contradicts previous preliminary assignment of the Langenberg atoposaurids to Theriosuchus. Knoetschkesuchus gen. nov. is characterized in particular by the presence of two dental morphotypes in the maxilla and dentary, slit-like secondary choanae within a narrow groove on the surface of the pterygoid, absence of lacrimonasal contact, presence of an antorbital foramen and an external mandibular fenestra, and proportional characters of the interorbital and intertemporal region. A similar combination of characters allows attribution of Theriosuchus guimarotae to Knoetschkesuchus, forming the new combination Knoetschkesuchus guimarotae. Our analysis provides an osteological basis for the separation of Theriosuchus and Knoetschkesuchus and helps further delineate generic differences in other closely related crocodylomorphs. Our phylogenetic analysis corroborates inclusion of Knoetschkesuchus into Atoposauridae and supports a position of Atoposauridae within Eusuchia.

[Emotion Regulation in Adolescents with Nonsuicidal Self-Injury]. / Emotionsregulation bei Jugendlichen mit Nichtsuizidalen Selbstverletzungen.

Nonsuicidal self-injury (NSSI) is a prevalent and impairing condition that was newly included in DSM-5 in the section III criteria for further research. Difficulties in emotion regulation play an important role in the development and maintenance of NSSI. This study investigated the emotion regulation in female adolescents with NSSI according to DSM-5 (n=55), clinical control adolescents with mental disorders without NSSI (n=30), and nonclinical control adolescents (n=58) using self-report questionnaires and interviews. As expected, results indicated that adolescents with NSSI have significantly more difficulties in emotion regulation compared to healthy controls. In addition, adolescents with NSSI reported also significantly more difficulties in impulse control, lack of emotional clarity, difficulties engaging in goal-directed behavior, and limited access to emotion regulation strategies compared to nonclinical and clinical controls. Adolescents with NSSI felt significantly more often sadness compared to clinical controls (d=0.66) and compared to other emotions. Adolescents with NSSI indicated significantly less often happiness compared to nonclinical controls (d=1.83). Results support that adolescents with NSSI have difficulties in emotion regulation and that these difficulties are even more pronounced than in adolescents with other mental disorders. Clinical implications will be discussed.

Dimensions of coping in chronic pain patients: factor analysis and cross-validation of the German version of the Coping Strategies Questionnaire (CSQ-D).

PURPOSE: The Coping Strategies Questionnaire (CSQ) by Rosenstiel and Keefe (1983) is one of the most widely used measures of coping strategies in pain patients, although its construct and factorial validity is dissatisfying. Verra, Angst, Lehmann, and Aeschlimann (2006) translated the full measure, which assesses eight different coping strategies, into German (CSQ-D). Our aim was to identify stable latent dimensions and present a shorter and more valid version of the CSQ-D. METHODS: A principal axes factor analysis (PFA) and a confirmatory factor analysis (CFA) were performed for specification and cross-validation of the new model. Thus, two independent samples of patients with fibromyalgia-like symptoms (n = 321, n = 162) completed questionnaire batteries that included the CSQ-D and measures of fibromyalgia (FM) impact, pain, depression, and anxiety. RESULTS: The most interpretable result appeared to be a six-factor model with an acceptable fit. The first four factors, (1) Catastrophizing, (2) Ignoring Pain, (3) Diversion, and (4) Reinterpreting Pain, resemble the original scales by Rosenstiel and Keefe (1983). The Praying or Hoping scale split up into distinct (5) Praying and (6) Hoping dimensions. Except Praying, all coping strategies were significantly associated with measures of psychological health outcomes, pain, overall FM impact, or social support. CONCLUSIONS: The new short form, called CSQ-DS, is a valid and reliable instrument, composed of 26 items and assessing six coping strategies. Future investigations are recommended to further prove both the external and construct validity of the CSQ-DS.

[Prevalence of mental disorders among college students at a German university]. / Prävalenz psychischer Syndrome bei Studierenden einer deutschen Universität.

BACKGROUND: Students are an important part of the general population of Germany, but only limited information exists about the prevalence of common psychological syndromes among them. OBJECTIVE: To provide prevalence rates for various psychological syndromes (affective, anxiety, somotoform, eating disorders, and alcohol associated problems) among German university students. METHODS: A campus-wide survey including N = 1130 students at the University of Mannheim was conducted. Established assessment instruments were employed for this purpose: the German version of the Patient Health Questionnaire (PHQ), the German Version of the Whiteley-Index (WI), and the Chemical Odor Sensitivity Scale (COSS) to screen for idiopathic environmental intolerance (IEI). RESULTS: PHQ criteria for at least one psychological disorder (apart from the alcohol abuse/dependence syndrome) were met by 22.7% of the students, more frequently by women than men (OR = 1.8). The alcohol syndrome (30.2%) was most frequent and the only syndrome which was more frequent in men than in women. The next frequent syndrome was the somatoform syndrome (9.1%), followed by other depressive syndromes (8.1 %), IEI (7.2%), major depression (6.0%) and hypochondriasis (4.2%). The presence of hypochondriasis increased greatly the risk for co-morbid disorders. All syndromes--with the exception of the alcohol syndrome and the binge eating disorder--were accompanied by functional impairments. CONCLUSIONS: We consider these results rather alarming, as they indicate a considerable need for both preventive and curative interventions in German students. However, further epidemiological studies are needed to prove the generalizability of our findings and to examine functional interrelations among and the course of these psychological syndromes.

Tuning the electronic properties of N-heterocyclic carbenes.

The electron-donating properties of N-heterocyclic carbenes ([N,N'-bis(2,6-dimethylphenyl)imidazol]-2-ylidene and the respective dihydro ligands) with 4,4'-R-substituted aryl rings (4,4'-R=NEt2, OC(12)H(25), Me, H, Br, S(4-tolyl), SO(4-tolyl), SO2(4-tolyl)) were studied. Twelve new N-heterocyclic carbene (NHC) ligands were synthesized as well as the respective iridium complexes [IrCl(cod)(NHC)] and [IrCl(CO)2(NHC)]. Cyclic voltammetry (DeltaE1/2) and IR (nu (CO)) can be used to measure the electron-donating properties of the carbene ligands. Modifying the 4-positions with electron-withdrawing substituents (4-R=-SO(2)Ar, DeltaE1/2=+0.92 V) results in NHC ligands with virtually the same electron-donating capacity as a trialkylphosphine in [IrCl(cod)(PCy3)] (DeltaE1/2 =+0.95 V), while [IrCl(cod)(NHC)] complexes with 4-R=NEt2 (DeltaE1/2= +0.59 V) show drastically more cathodic redox potentials and significantly enhanced donating properties.

Novel reconstruction of the orientation of the pectoral girdle in sauropods.

The orientation of the scapulocoracoid in sauropod dinosaurs is reconstructed based on comparative anatomical investigations of pectoral girdles of extant amniotes. In the reconstruction proposed here, the scapula of sauropods stands at an angle of at least 55 degrees to the horizontal plane in mechanical coherence with the sternal apparatus including the coracoids. The coracoids are oriented cranioventrally to the rib cage and the glenoid is directed mediolaterally, which allows the humerus to swing in a sagittal plane. The inclination of the scapula to the horizontal plane is reconstructed for Diplodocus (60-65 degrees), Camarasaurus (60-65 degrees), and Opisthocoelicaudia (55-65 degrees). The inclination of the scapulocoracoid has consequences for the overall body posture in Camarasaurus and Opisthocoelicaudia, where the dorsal contour would have ventrally declined toward the sacrum. Scapulocoracoid mobility depends on the arrangement of clavicles, the reconstruction of a coracosternal joint, and the reconstructed musculature of the shoulder girdle. In a crocodylian model of the shoulder musculature, m. serratus profundus and superficialis form a muscular sling, which suspends the trunk from the shoulder girdle and would allow a certain mobility of the scapulocoracoid. An avian model of the shoulder musculature would also mean suspension by means of the m. serratus complex, but indicates a closer connection of the scapula to the dorsal ribs, which would lead to more restricted movements of the scapulocoracoid in sauropods.