Glycine‐modified growth hormone secretagogues identified in seized doping material

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography–high resolution mass spectrometry (LC–HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP‐2 (Pralmorelin), GHRP‐6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1–29), which can be used as performance‐enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N‐terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.     

GLI1-induced mammary gland tumours are transplantable and maintain major molecular features

Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-like^Ex, Class8^Ex, Claudin-Low^Ex and Erbb2-like^Ex. The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression.     

A proposal for the classification of dental alloys according to their resistance to corrosion.

OBJECTIVES: The purpose of this study was to establish a method to compare and classify dental alloys in relation to their resistance to corrosion. METHODS: Alloy samples and pure metal samples were prepared and tested in chemical and electrochemical corrosion according to ISO 10271. For electrochemical test, the rest potential versus time and a potentiodynamic scan were recorded. After chemical corrosion test, the ions released were analyzed by ICP (induced coupled plasma) spectroscopy. RESULTS: High gold alloys had a similar polarization curve than gold. The same effect was observed for Pd-base alloys, their curves were similar to the one of palladium. The ions released during chemical corrosion were non-precious metallic ions. Thereby Ni-Cr alloys were found to release the most ions. Au-Pt alloys showed the highest release of ions compared with other precious alloys but low compared with Ni-Cr. Electrochemical corrosion was more aggressive than chemical corrosion and every type of elements was etched, the higher the precious metal content, the higher the resistance to corrosion of the alloy. DISCUSSION: Using the recorded data, a classification system for electrochemical corrosion was developed and discussed to judge the results. Hereby were gold and zinc used as reference materials. The applied classification system defines five classes and it is proposed that alloys of class V are not acceptable. For chemical corrosion resistance, three classes were distinguished according to the quantity of metallic ions released and it is proposed that class III (100-1000 microg/cm(2)week) is not acceptable. Palladium and Pd-base alloys showed a higher electrochemical and chemical corrosion resistance than gold.     

Serum cytokine levels in periodontitis patients in relation to the bacterial load

Background: Periodontitis is a local inflammatory disease that also has some systemic effects. We investigated the levels of interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐2, ‐4, ‐5, and ‐10 in the serum of patients with periodontitis in relation to the bacterial load in the dental plaques. Methods: Serum cytokine levels in patients with generalized periodontitis and healthy control groups were determined using the cytometric bead array kit. Bacterial load in the dental plaque was determined semiquantitatively by real‐time polymerase chain reaction. The proportions of different lymphocyte subsets were determined in the peripheral blood of patients with periodontitis by flow cytometry. Finally, relationships between the bacterial load in the subgingival plaques of patients with periodontitis and levels of cytokines and counts of lymphocyte subsets were established. Results: Serum levels of IFN‐γ, TNF‐α, and IL‐10 were significantly increased, whereas those of IL‐2 were significantly decreased in patients with periodontitis compared to healthy controls. Increased serum levels of IFN‐γ and TNF‐α in patients with periodontitis were associated with the enhanced dental plaque load with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Porphyromonas gingivalis, respectively. Finally, as revealed by analysis of lymphocyte populations, the presence of A. actinomycetemcomitans and Trepomena denticola was associated with an increased population of CD3^?/CD16⁺ and CD3⁺/CD8⁺ cells, respectively. Conclusion: Certain periodontal pathogens could be associated with an increased level of proinflammatory cytokines in the peripheral blood and thus increased risk of systemic diseases.     

Network Analysis of Posttraumatic Stress Experiences of Adults Seeking Psychological Treatment for Childhood Sexual Abuse

Network analysis proposes that mental disorders may best be construed as causal systems embodied in networks of functionally interconnected symptoms. We employed network analysis to test how adult survivors of childhood sexual abuse (CSA) experienced symptoms of posttraumatic stress, using alternative conceptualizations of posttraumatic stress disorder (PTSD). Given the characteristics of the sample (i.e., the nature of and time since trauma), we hypothesized that (a) symptoms related to arousal would not be prominent in the networks and (b) symptoms related to negative alternations in cognition and mood (NACM) would be core components in the network. Danish adults seeking psychological treatment for CSA (n = 473) completed the Harvard Trauma Questionnaire and Trauma Symptom Checklist. Three alternative models (DSM-5, DSM-5 with dissociation, and ICD-11 complex PTSD [CPTSD]) were estimated using regularized partial correlation models. In the DSM-5 network, strong associations emerged for experiences of NACM (blame and guilt) and intrusions (thoughts and flashbacks). The addition of “depersonalization” and “derealization” to the DSM-5 model produced a strong association, but these experiences were largely unrelated to other PTSD clusters. In the CPTSD network, interpersonal problems and negative self-concept were central to the survivors’ experiences. For this highly-specific survivor group who experienced traumatic CSA many years ago, experiences related to NACM appeared to be more central to the posttrauma experience than those of arousal. If replicated, these findings could help inform treatment plans for specific groups of survivors. Methodological implications as to the usefulness of network models in the psychopathological research literature are discussed.     

Photobiomodulation via a cluster device associated with a physical exercise program in the level of pain and muscle strength in middle-aged and older women with knee osteoarthritis: a randomized placebo-controlled trial

Osteoarthritis (OA) is a chronic joint disease that leads to pain and functional incapacity. The aim of the study is to investigate the effects of the incorporation of photobiomodulation (PBM) (via cluster) into a physical exercise program on the level of pain, lower limb muscle strength, and physical capacity, in patients with knee OA. Sixty-two female volunteers with a diagnosis of knee OA were distributed in 4 groups: exercise associated with placebo PBM group, exercise associated with active PBM group, active PBM group, and placebo PBM group. Sixteen sessions of lower limb strength exercises and PBM via cluster (808 nm, 100 mW, 7 points each side, 56 J total) were performed. The level of pain, physical capacity, and lower limb muscle strength were evaluated with the use of the numeric pain rating scale (NPRS), 6-min walking test (6-MWT) and timed up and go (TUG), and maximal voluntary isometric torque (MVIT) before and after the interventions. Both groups presented a significant decrease in the level of pain when compared with the placebo-treated women. Furthermore, the 6-MWT showed that the trained groups (with or without PBM) demonstrated higher values in the distance walked comparing pre and post-treatment values. The same behavior was found for the MVIT load before and after intervention. TUG was higher for all the treated with exercise groups comparing the pre and post-treatment values. Physical exercise and PBM showed analgesic effects. However, PBM did not have any extra effect along with the effects of exercise in improving the distance walked, the TUG, and the muscle strength.

Trial registration: RBR-7t6nzr