Maladaptive emotion regulation strategies mediate the relationship between biased cognitions and depression

Introduction: Depression has previously been found to emerge from and be perpetuated by negative cognitive biases. However, a plethora of underlying psychological mechanisms are likely to be involved in the relationship. The current study investigated whether maladaptive cognitive emotion regulation strategies such as self-blame, rumination, and catastrophising may mediate the link between negative cognitive biases and depression.Methods: Participants (n = 251) completed the study via the internet data collection software, Pavlovia. The Self-Referent Encoding Task was used to measure self-referential and memory biases while maladaptive emotion regulation strategies and depression were assessed using the Cognitive Emotion Regulation Questionnaire and the Depression Anxiety Scales, respectively.Results: Results showed that maladaptive strategies mediate the relationship between cognitive biases and depression. The tendency to blame oneself for playing an influential role in a negatively perceived life event seems to play a key role in the negative cognitive bias-depression relationship.Conclusion: Therapists should consider focusing their efforts on reducing self-blame when clients demonstrate evidence of self-referential and memory bias. Interventions may include refocusing blame on others, rather than the self

Isolated familial pheochromocytoma as a variant of von Hippel-Lindau disease.

Inherited pheochromocytomas are often part of familial syndromes, especially multiple endocrine neoplasia type 2 (MEN 2), retinal cerebellar hemangioblastomatosis [von Hippel-Lindau (vHL) disease] or neurofibromatosis type 1. It is not clear whether isolated familial pheochromocytoma exists as a separate clinical entity. In a family with pheochromocytomas in three generations and with at least seven affected members, we investigated by clinical and genetic analyses the presence or absence of associated conditions. The clinical investigations included ophthalmological and radiological studies for von Hippel-Lindau disease (magnetic resonance imaging of the brain, computed tomography of the abdomen, and direct ophthalmoscopy after mydriasis) and annual calcitonin stimulation tests for C cell disease in five members who agreed to regular follow-up. Besides the pheochromocytomas (so far, these have been multiple in five of seven individuals) no definite second associated condition was found. Genetic analysis did not identify any MEN 2-specific RET protooncogene point mutations (which are present in 97% of MEN 2a families). However, despite the complete absence of other clinical manifestations of the vHL disease (besides pheochromocytomas), a previously undescribed germline missense mutation in the vHL tumor suppressor gene was found (C775G transversion with a predicted substitution of a leucine by a valine at codon 259 in the putative vHL protein). We conclude that in this family the sole occurrence of pheochromocytoma is a variant of vHL disease

Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy

Sustainable Health Development Goals (SHDG): breaking down the walls.

The worlds governments failed to achieve the Health for All 2000 goals from the Alma Ata Declaration of 1978. Although a lot of milestones have been covered since 2000, the worlds governing authorities are unlikely to achieve the current Millennium Development Goals (MDGs) which expire by the end of this year. The inability to achieve these goals may be linked to the multiplicity of health-related directives and fragmentation of health systems in many countries. However, with the proposed 17 sustainability development goals, health has only one universal aim: to ensure healthy lives and promote wellbeing for all at all ages. Accomplishing this will require a focus on health systems (system-thinking), commonization of services and full integration of services with total dismantling of vertical programs across the world

Etablierung einer Kollagenase-freien Methode zur Untersuchung regulatorischer T-Zellen in Tumorfrischgewebe des Nierenzellkarzinoms

Renal cell carcinoma is a malignant tumor with a steadily increasing incidence rate in adult-hood. The malignancy potential differs depending on the histology, however, surgical treatment is currently the only curative approach. At the time of diagnosis, 20-30 % of RCC have already metastasized and as part of the follow-up after nephrectomy, metastases occur within 36 to 48 months in 13-30 % of the cases, depending on the primary stage. In these cases, a systemic therapy is recommended. However, increased ABC transporter expression in the carcinoma cells (in particular of p-glycoprotein) can lead to a natural resistance of the tumor cells to conventional chemotherapeutic agents. Therapy of metastatic renal cell carcinoma therefore takes place as part of systemic therapy using multi-kinase inhibitors, cytokines, mTOR inhibitors and checkpoint inhibitors. Against the background of heterogenous response to immunotherapy, the immunomodulatory activity of the regulatory T cells (Treg) is the subject of research. Of particular interest regarding the modulation of anti-tumor defense is the endogenous immunosuppression by Treg cells. For this purpose, an efficient isolation method of tumor-infiltrating lymphocytes (TIL) from fresh tumor tissue with high vital cell yield and a sufficient amount of intact TIL is indispensable. Up to now, tissue digestion protocols based on collagenase have been used as the standard method for TIL isolation for subsequent further cell analysis. Collagenase is a naturally oc-curring peptidase in humans and exists in different subtypes. Due to the high vital cell yield, this method has long been considered the method of choice. However, the proteolytic nature of collagenase is known to result in modifications of membrane-bound receptors and other surface molecules on the T cells. The latter proves to be problematic since intact cell structures and surface protein profiles are an indispensable prerequisite for high-resolution flow cytometric measurements or functional in vitro cell culture assays. In order to analyze the Treg cell populations in the kidney tumor tissue more accurately by means of immunofluorescence methods, we first used the standard collagenase method to produce a single cell suspension according to established protocols. We found that the collagenase-based enzymatic tissue digestion protocol had a significantly negative effect on the fluorescence intensity of different surface markers. This led to a distortion of the flow cytometry results. In contrast, a collagenase-free protocol allowed more detailed and accurate analysis of T cells and Treg cells. A combined enzymatic-mechanical, as well as a purely mechanical method (MiniLys ©) were therefore investigated. The purely mechanical tissue dissociation was found to be equivalent to the standard protocol in terms of cell yield. Moreover, the cell yield was significantly higher in tumors of hard consistency than the purely enzymatically processed samples. Furthermore, the MiniLys © protocol is not only less time-consuming, but also requires a smaller amount of tumor material. This efficiency of the isolation method is particularly relevant with regard to the stage distribution in RCC diagnosis, as an estimated 65 % are being operated at the locally limited stage of the disease (Howlader N 2018). The present thesis shows that the purely mechanical method represents a possible alternative to the enzymatic digestion and that it can be significantly superior with respect to efficiency and accuracy. As a result, the "Mini-Lys" © protocol "a-20 sec" could be established as a new standard operation procedure (SOP) for the future production of single cell suspension from fresh kidney tumor tissue.Das Nierenzellkarzinom (NZK) ist ein maligner Tumor mit stetig steigender Inzidenzrate im Erwachsenenalter. Das Malignitätspotential differiert je nach Histologie, jedoch gilt in allen Fällen die operative Therapie als der einzige kurative Ansatz. Zum Zeitpunkt der Diagnosestellung liegt in 20-30 % der Fälle bereits ein metastasiertes NZK vor und im Rahmen des follow-ups nach Nephrektomie treten in Abhängigkeit vom Primärstadium in 13-30 % der Fälle innerhalb von 36 bis 48 Monaten Metastasen auf. In diesen Fällen wird eine systemische Therapie empfohlen. Das in den Karzinomzellen erhöhte ABC-Transporter-Expressionslevel (im Speziellen p-Glykoprotein) führt jedoch zu einer natürlichen Resistenz der Tumorzellen gegenüber konventionellen Chemotherapeutika. Die Therapie des metastasierten NZK erfolgt daher im Rahmen der Systemtherapie mittels Multi-Kinase-Inhibitoren, Zytokinen, mTOR-Inhibitoren und Checkpoint-Inhibitoren. Vor dem Hintergrund des heterogenen Ansprechens auf die Immuntherapie ist die immunmodulatorische Aktivität der regulatorischen T-Zellen (Treg) Gegenstand der Forschung. Von maßgeblichem Interesse ist insbesondere die endogene Immunsuppression durch die Treg-Zellen. Im Rahmen einer Immuntherapie besteht hier ein Ansatzpunkt, um eine optimale Modulation mit verstärkter Tumorabwehr zu erreichen. Zu diesem Zweck ist eine effiziente Isolationsmethode von TIL aus Tumorfrischgewebe mit hoher vitaler Zellausbeute und einer aus-reichenden Menge an intakten TIL unabdingbar. Als Standardmethode zur Isolation von tumorinfiltrierenden T-Zellen im Rahmen der weiter-führenden Zellanalyse dienen bisher meist Protokolle, die Kollagenase zum Gewebeaufschluss verwenden. Die Kollagenase ist eine natürlicherweise beim Menschen vorkommende Peptidase und liegt in unterschiedlichen Subtypen vor. Aufgrund der hohen vitalen Zell-ausbeute galt diese Methode lange Zeit als Mittel der Wahl. Durch die proteolytische Eigenschaft der Kollagenase kommt es jedoch unter anderem zu einer Veränderung membrangebundener Rezeptoren und Oberflächenmoleküle von T-Zellen. Dies erweist sich als problematisch, da intakte Zellstrukturen und Oberflächenmolekülprofile eine unabdingbare Voraussetzung für hochauflösende durchflusszytometrische Messungen oder in vitro Zellkultur-Assays darstellen. Um die Treg-Zellpopulationen im Nierentumorgewebe mittels Immunfluoreszenzverfahren genauer analysieren zu können, verwendeten wir gemäß etablierter Protokolle zunächst das Kollagenase-basierte Protokoll zur Herstellung einer Einzelzellsuspension. Wir stellten fest, dass sich der enzymatische Gewebeaufschluss signifikant negativ auf die Fluoreszenzintensität unterschiedlicher Oberflächenmarker auswirkte. Dies führte zu einer Verfälschung der durchflusszytometrischen Messergebnisse, sodass zur genaueren Analyse der T-Zellen und auch der Treg-Zellen die Etablierung eines kollagenasefreien Protokolls notwendig war. Es wurden im Vergleich zur rein enzymatischen Methode eine kombiniert enzymatisch-mechanische und eine rein mechanische Methode (MiniLys©) untersucht. Der rein mechanische Gewebeaufschluss zeigte sich in Bezug auf die Zellausbeute als gleichwertig. Im Hinblick auf die Gewebestruktur zeigte sich diese Methode bei Tumoren von harter Konsistenz sogar signifikant überlegen gegenüber den rein enzymatisch prozessierten Proben. Des Weiteren zeichnet sich das MiniLys©-Protokoll neben einem geringeren Zeitaufwand insbesondere durch eine geringe Menge an benötigtem Tumormaterial aus. Diese Effizienz der Isolationsmethode ist besonders relevant im Hinblick auf die Stadienverteilung bei Diagnose des NZK. So wird aktuell in 65 % der Fälle im lokal begrenzten Stadium der Erkrankung operiert (Howlader N 2018). Die vorliegende Arbeit zeigt, dass die rein mechanische Methode eine mögliche Alternative zum enzymatischen Verdau darstellt und dieser in den oben genannten Punkten teilweise signifikant überlegen ist. Als Ergebnis konnte daher das „MiniLys“©-Protokoll „a-20 Sek.“ als neues Standardprotokoll (SOP) zur zukünftigen Herstellung von Einzel-Zellsuspension aus frischem Nierentumorgewebe etabliert werden

Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Getting our act together: an exploration of the mechanisms responsible for the affiliative changes evoked by interpersonal movement

This thesis explores the reasons why dyads whose movements are aligned (i.e., synchronous) report greater levels of affiliation than those whose movements are not (i.e., asynchronous). Though previous research has suggested that outcomes are influenced by self-other overlap, via action co-representation and/or self-other similarity, none has examined this directly, or considered the effects of participants' judgements about their co-actor's relative performance. Previous research has also neglected the fact that dyadic movement can be aligned or misaligned in a variety of ways (e.g., topologically in terms of what movements are made and temporally in terms of when the movements are made), providing little evidence for the mechanisms supporting the alignment-affiliation relationship. Across three experiments, dyads (N=534; 267 dyads) were randomly assigned to perform arm movements that were aligned or misaligned temporally or topologically. Control participants made matching arm movements while facing away from their co-actor, removing visual alignment cues and controlling for the effects of movement. Action co-representation, self-other similarity, and interaction judgments about alignment with the co-actor were tested. Evidence was found favouring the role of meta-judgments, while alignment, but not misalignment, affected affiliation. These findings suggest that high order judgments, and not self-other merging, may be responsible

Challenges of liver cancer: Future emerging tools in imaging and urinary biomarkers.

© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.Chronic liver disease has become a global health problem as a result of the increasing incidence of viral hepatitis, obesity and alcohol misuse. Over the past three decades, in the United Kingdom alone, deaths from chronic liver disease have increased both in men and in women. Currently, 2.5% of deaths worldwide are attributed to liver disease and projected figures suggest a doubling in hospitalisation and associated mortality by 2020. Chronic liver diseases vary for clinical manifestations and natural history, with some individuals having relatively indolent disease and others with a rapidly progressive course. About 30% of patients affected by hepatitis C has a progressive disease and develop cirrhosis over a 20 years period from the infection, usually 5-10 years after initial medical presentation. The aim of the current therapeutic strategies is preventing the progression from hepatitis to fibrosis and subsequently, cirrhosis. Hepatic steatosis is a risk factor for chronic liver disease and is affecting about the half of patients who abuse alcohol. Moreover non-alcoholic fatty liver disease is part of the metabolic syndrome, associated with obesity, hypertension, type ? diabetes mellitus and dyslipidaemia, and a subgroup of patients develops non-alcoholic steatohepatitis and fibrosis with subsequent cirrhosis. The strengths and pitfalls of liver biopsy are discussed and a variety of new techniques to assess liver damage from transient elastography to experimental techniques, such as in vitro urinary nuclear magnetic resonance spectroscopy. Some of the techniques and tests described are already suitable for more widespread clinical application, as is the case with ultrasound-based liver diagnostics, but others, such as urinary metabonomics, requires a period of critical evaluation or development to take them from the research arena to clinical practice