Understanding pain in modern society: insights from attitudes to pain in the Medieval Period

Historical records provide knowledge about the way people lived in the past. Our perspective is that historical analyses of the Medieval Period provide insights to inform a fuller understanding of pain in the present era. In this article, we appraise critiques of the writings of people living with pain during the mid (high) to late Medieval Period (c. 1,000–1,500 AD) to gain insights into the nature, attitudes, lived experience, and sense-making of pain. In the Medieval Period, pain was understood in terms of Galen's four humours and the Church's doctrine of pain as a “divine gift”, “punishment for sin” and/or “sacrificial offering”. Many treatments for pain were precursors of those used in modern time and society considered pain to be a “shared experience”. We argue that sharing personal stories of life is a fundamental human attribute to foster social cohesion, and that nowadays sharing personal stories about pain is difficult during biomedically-focussed time-constrained clinical consultations. Exploring pain through a medieval lens demonstrates the importance of sharing stories of living with pain that are flexible in meaning, so that people can connect with a sense of self and their social world. We advocate a role for community-centred approaches to support people in the creation and sharing of their personal pain stories. Contributions from non-biomedical disciplines, such as history and the arts, can inform a fuller understanding of pain and its prevention and management

Combinatorial Effect of Non-Steroidal Anti-inflammatory Drugs and NF-κB Inhibitors in Ovarian Cancer Therapy

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer

A history of carpal tunnel syndrome

Carpal tunnel syndrome is the commonest entrapment neuropathy seen in clinical practice. The history of its aetiology and diagnosis gives an interesting insight into how the condition has evolved to also become the best understood neuropathy.N.S. Wardle, N. Pourgiezis, N. Ashwood, G.I. Bainhttp://www.ncbi.nlm.nih.gov/pubmed/1855754

Tuning Singlet Fission in π-Bridge-π Chromophores

We have designed a series of pentacene dimers separated by homoconjugated or nonconjugated bridges that exhibit fast and efficient intramolecular singlet exciton fission (iSF). These materials are distinctive among reported iSF compounds because they exist in the unexplored regime of close spatial proximity but weak electronic coupling between the singlet exciton and triplet pair states. Using transient absorption spectroscopy to investigate photophysics in these molecules, we find that homoconjugated dimers display desirable excited-state dynamics, with significantly reduced recombination rates as compared to conjugated dimers with similar singlet fission rates. In addition, unlike conjugated dimers, the time constants for singlet fission are relatively insensitive to the interplanar angle between chromophores, since rotation about σ bonds negligibly affects the orbital overlap within the π-bonding network. In the nonconjugated dimer, where the iSF occurs with a time constant >10 ns, comparable to the fluorescence lifetime, we used electron spin resonance spectroscopy to unequivocally establish the formation of triplet-triplet multiexcitons and uncoupled triplet excitons through singlet fission. Together, these studies enable us to articulate the role of the conjugation motif in iSF

Tuning Singlet Fission in π-Bridge-π Chromophores

We have designed a series of pentacene dimers separated by homoconjugated or non-conjugated bridges that exhibit fast and efficient intramolecular singlet exciton fission (iSF). These materials are distinctive among reported iSF compounds because they exist in the unexplored regime of close spatial proximity but weak electronic coupling between the singlet exciton and triplet pair states. Using transient absorption spectroscopy to investigate photophysics in these molecules, we find that homoconjugated dimers display desirable excited state dynamics, with significantly reduced recombination rates as compared to conjugated dimers with similar singlet fission rates. In addition, unlike conjugated dimers, the time constants for singlet fission are relatively insensitive to the interplanar angle between chromophores, since rotation about σ bonds negligibly affects the orbital overlap within the π-bonding network. In the non-conjugated dimer, where the iSF occurs with a time constant > 10 ns, comparable to the fluorescence lifetime, we used electron spin resonance spectroscopy to unequivocally establish the formation of triplet-triplet multiexcitons and uncoupled triplet exciton through singlet fission. Together, these studies enable us to articulate the role of the conjugation motif in iSF.L.M.C. acknowledges support from the Office of Naval Research Young Investigator Program (award N00014-15-1- 2532) and Cottrell Scholar Award. S.N.S., A.B.P., and B.C. thank the NSF for GRFP (DGE 11-44155). This research used resources of the Center for Functional Nanomaterials, which is a U.S. DOE Office of Science Facility, at Brookhaven National Laboratory under contract no. DE-SC0012704. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1548562. M.J.Y.T. acknowledges receipt of an ARENA Postdoctoral Fellowship and a Marie Sklodowska Individual Fellowship. D.R.M. acknowledges support from an Australian Research Council Future Fellowship (FT130100214) and through the ARC Centre of Excellence in Exciton Science (CE170100026). Single crystal X-ray diffraction was performed at the Shared Materials Characterization Laboratory at Columbia University. Use of the SMCL was made possible by funding from Columbia University. N.A. acknowledges support from the NSF CAREER (award no. CHE-1555205), NSF EAGER (award no. CHE-1546607), and a Sloan Foundation Research Fellowship. J.C.D. and G.D.S. acknowledge funding through the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U.S. Department of Energy (award no. DESC0015429)