Pain psychology in the 21st century: lessons learned and moving forward

Background and aims In the spring of 2019, Professor Steven J. Linton, the founder of the Center for Health and Medical Psychology (CHAMP) at Örebro University, Sweden, formally retired. As a tribute to his scholarly work covering decades of influence and inspiration to the field of pain psychology, the research center organized a topical conference titled “Pain in the 21st century: Where do we come from and where are we going?”, which resulted in this state-of the-art synthesis. The aim of this declaration is to highlight lessons learned but not in the least is meant to inspire and guide our continued journey forward, developing pain psychology into the 21st century. Methods Several collaborators of Professor Linton have summarized and reflected on the current state-of-the-art of pain psychology from the perspective of his input to the field, as well as on developments from the last years of advancements in pain psychology. Results The topics have been divided into six themed sections covering the fear avoidance model, transdiagnostics, secondary prevention, risk- and protective factors, communication and contextual factors. The sections cover a broad spectrum, from basic experimental studies, integrating emotion and motivational theories into current theoretical models, to applied research on the effect of early interventions as well as sophisticated emotion-focused treatment models for pain patients with concurrent emotional ill-health. Conclusions There have been major advancements within pain psychology research during the last decades, moving the field towards a more comprehensive picture, taking emotional and motivational aspects into account to understand pain sufferers. Although psychologically informed interventions in general mainly focus on the individual, it has been put forward that pain management is highly influenced by the surrounding environment, including communication with health care providers, and the occupational and social context. Implications Professor Steven J. Linton has been at the forefront of pain psychology research during the last decades, and inspired by his work this journey will continue into the 21st century, with the ultimate goal of enhancing the understanding and treatment for all people suffering from persistent and disabling pain

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages

Common Avian Infection Plagued the Tyrant Dinosaurs

Background: Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name 'Sue') has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids

Development of the lateral ventricular choroid plexus in a marsupial, Monodelphis domestica

<p>Abstract</p> <p>Background</p> <p>Choroid plexus epithelial cells are the site of blood/cerebrospinal fluid (CSF) barrier and regulate molecular transfer between the two compartments. Their mitotic activity in the adult is low. During development, the pattern of growth and timing of acquisition of functional properties of plexus epithelium are not known.</p> <p>Methods</p> <p>Numbers and size of choroid plexus epithelial cells and their nuclei were counted and measured in the lateral ventricular plexus from the first day of its appearance until adulthood. Newborn <it>Monodelphis </it>pups were injected with 5-bromo-2-deoxyuridine (BrdU) at postnatal day 3 (P3), P4 and P5. Additional animals were injected at P63, P64 and P65. BrdU-immunopositive nuclei were counted and their position mapped in the plexus structure at different ages after injections. Double-labelling immunocytochemistry with antibodies to plasma protein identified post-mitotic cells involved in protein transfer.</p> <p>Results</p> <p>Numbers of choroid plexus epithelial cells increased 10-fold between the time of birth and adulthood. In newborn pups each consecutive injection of BrdU labelled 20-40 of epithelial cells counted. After 3 injections, numbers of BrdU positive cells remained constant for at least 2 months. BrdU injections at an older age (P63, P64, P65) resulted in a smaller number of labelled plexus cells. Numbers of plexus cells immunopositive for both BrdU and plasma protein increased with age indicating that protein transferring properties are acquired post mitotically. Labelled nuclei were only detected on the dorsal arm of the plexus as it grows from the neuroependyma, moving along the structure in a 'conveyor belt' like fashion.</p> <p>Conclusions</p> <p>The present study established that lateral ventricular choroid plexus epithelial cells are born on the dorsal side of the structure only. Cells born in the first few days after choroid plexus differentiation from the neuroependyma remain present even two months later. Protein-transferring properties are acquired post-mitotically and relatively early in plexus development.</p

JISTIC: Identification of Significant Targets in Cancer

<p>Abstract</p> <p>Background</p> <p>Cancer is caused through a multistep process, in which a succession of genetic changes, each conferring a competitive advantage for growth and proliferation, leads to the progressive conversion of normal human cells into malignant cancer cells. Interrogation of cancer genomes holds the promise of understanding this process, thus revolutionizing cancer research and treatment. As datasets measuring copy number aberrations in tumors accumulate, a major challenge has become to distinguish between those mutations that drive the cancer versus those passenger mutations that have no effect.</p> <p>Results</p> <p>We present JISTIC, a tool for analyzing datasets of genome-wide copy number variation to identify driver aberrations in cancer. JISTIC is an improvement over the widely used GISTIC algorithm. We compared the performance of JISTIC versus GISTIC on a dataset of glioblastoma copy number variation, JISTIC finds 173 significant regions, whereas GISTIC only finds 103 significant regions. Importantly, the additional regions detected by JISTIC are enriched for oncogenes and genes involved in cell-cycle and proliferation.</p> <p>Conclusions</p> <p>JISTIC is an easy-to-install platform independent implementation of GISTIC that outperforms the original algorithm detecting more relevant candidate genes and regions. The software and documentation are freely available and can be found at: <url>http://www.c2b2.columbia.edu/danapeerlab/html/software.html</url></p