- Misery to Mirth: Recovery from Illness in Early Modern England [BOOK]
- BOOKOxford University Press: Oxford (UK)
- The history of early modern medicine often makes for depressing reading. It implies that people fell ill, took ineffective remedies, and died. This book seeks to rebalance and brighten our overall pi…
The history of early modern medicine often makes for depressing reading. It implies that people fell ill, took ineffective remedies, and died. This book seeks to rebalance and brighten our overall picture of early modern health by focusing on the neglected subject of recovery from illness in England, c.1580–1720. Drawing on an array of archival and printed materials, Misery to Mirth shows that recovery did exist conceptually at this time, and that it was a widely reported phenomenon. The book takes three main perspectives: the first is physiological or medical, asking what doctors and laypeople meant by recovery, and how they thought it occurred. This includes a discussion of convalescent care, a special branch of medicine designed to restore strength to the patient’s fragile body after illness. Secondly, the book adopts the viewpoint of patients themselves: it investigates how they reacted to the escape from death, the abatement of pain and suffering, and the return to normal life and work. At the heart of getting better was contrast—from ‘paine to ease, sadnesse to mirth, prison to liberty, and death to life’. The third perspective concerns the patient’s loved ones; it shows that family and friends usually shared the feelings of patients, undergoing a dramatic transformation from anguish to elation. This mirroring of experiences, known as ‘fellow-feeling’, reveals the depth of love between many individuals. Through these discussions, the book opens a window onto some of the most profound, as well as the more prosaic, aspects of early modern existence, from attitudes to life and death, to details of what convalescents ate for supper and wore in bed.
- Sensitive Skin: Lessons From Transcriptomic Studies. [Review]
- FMFront Med (Lausanne) 2019; 6:115
- In 2016, a special interest group from the International Forum for the Study of Itch defined sensitive skin (SS) as a syndrome that manifests with the occurrence of unpleasant sensations (stinging, b…
In 2016, a special interest group from the International Forum for the Study of Itch defined sensitive skin (SS) as a syndrome that manifests with the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) after stimuli that should not cause a reaction, such as water, cold, heat, or other physical and/or chemical factors. The pathophysiology of sensitive skin is still poorly understood, but the symptoms described suggest inflammation and peripheral innervation. Only two publications have focused on sensitive skin transcriptomics. In the first study, the authors performed a microarray comparison of SS and non-sensitive skin (NSS) samples and showed differences in the expression of numerous genes in SS and NSS samples. Moreover, in the SS samples, two clusters of genes were identified, including upregulated and downregulated genes, compared to NSS samples. These results provide some interesting clues for the understanding of the pathophysiology of SS. The second study compared SS and NSS samples using RNA-seq assays. This method allowed the identification of long non-coding RNAs (lncRNAs) and differentially expressed mRNAs and provided a comprehensive profile in subjects with SS. The results showed that a wide range of genes may be involved in the pathogenesis of SS and suggested pathways that could be associated with them. In this paper, we discuss these two studies in detail and show how transcriptomic studies can help understand the pathophysiology of sensitive skin. We call for new transcriptomic studies on larger populations to be conducted before putative pathogenic mechanisms can be detected and analyzed to achieve a better understanding of this complex condition.
- Immune Checkpoint Inhibitors in Melanoma: A Review of Pharmacokinetics and Exposure-Response Relationships. [Journal Article]
- CPClin Pharmacokinet 2019 Jun 10
- Immune checkpoint inhibitors are a new class of monoclonal antibodies that amplify T-cell-mediated immune responses against cancer cells. The introduction of these new drugs, first anti-cytotoxic T-l…
Immune checkpoint inhibitors are a new class of monoclonal antibodies that amplify T-cell-mediated immune responses against cancer cells. The introduction of these new drugs, first anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and then anti-programmed death-1 (anti-PD1), was a major improvement in the treatment of advanced or metastatic melanoma, a highly immunogenic tumour. The development strategy for immune checkpoint immunotherapies differed from that traditionally used for cytotoxic therapies in oncology. The choices of doses at which to conduct clinical trials, and subsequently the choice of doses at which to use these new therapies, were not based on the identification of a maximum tolerated dose from dose-escalation studies; thus, pharmacokinetic and pharmacokinetic-pharmacodynamic modelling was essential. The studies conducted have shown that the pharmacokinetics of ipilimumab were linear and not time-dependent. In addition, there was a correlation between the trough concentrations of ipilimumab and its therapeutic efficacy. On the contrary, the anti-PD1 immunotherapies nivolumab and pembrolizumab had time-dependent pharmacokinetics. Their therapeutic efficacy was not related to their trough concentration, but there was a correlation between the clearance of anti-PD1 and the survival of melanoma patients. This review highlights the complexity of interpreting the exposure-response relationships of these agents. Further studies are needed to assess the value of therapeutic drug monitoring of immune checkpoint inhibitors in the treatment of melanoma.
- ACP-DL: A Deep Learning Long Short-Term Memory Model to Predict Anticancer Peptides Using High-Efficiency Feature Representation. [Journal Article]
- MTMol Ther Nucleic Acids 2019 May 10; 17:1-9
- Cancer is a well-known killer of human beings, which has led to countless deaths and misery. Anticancer peptides open a promising perspective for cancer treatment, and they have various attractive ad…
Cancer is a well-known killer of human beings, which has led to countless deaths and misery. Anticancer peptides open a promising perspective for cancer treatment, and they have various attractive advantages. Conventional wet experiments are expensive and inefficient for finding and identifying novel anticancer peptides. There is an urgent need to develop a novel computational method to predict novel anticancer peptides. In this study, we propose a deep learning long short-term memory (LSTM) neural network model, ACP-DL, to effectively predict novel anticancer peptides. More specifically, to fully exploit peptide sequence information, we developed an efficient feature representation approach by integrating binary profile feature and k-mer sparse matrix of the reduced amino acid alphabet. Then we implemented a deep LSTM model to automatically learn how to identify anticancer peptides and non-anticancer peptides. To our knowledge, this is the first time that the deep LSTM model has been applied to predict anticancer peptides. It was demonstrated by cross-validation experiments that the proposed ACP-DL remarkably outperformed other comparison methods with high accuracy and satisfied specificity on benchmark datasets. In addition, we also contributed two new anticancer peptides benchmark datasets, ACP740 and ACP240, in this work. The source code and datasets are available at https://github.com/haichengyi/ACP-DL.
- Emerging Treatments and Novel Pathways in Pruritus. [Journal Article]
- JCJ Cutan Med Surg 2019 Jun 06; :1203475419852050
- Itch treatment is a major challenge in the dermatologist's practice. We encounter patients suffering from pruritus on a regular basis, and often lack diverse treatment options to adequately respond t…
Itch treatment is a major challenge in the dermatologist's practice. We encounter patients suffering from pruritus on a regular basis, and often lack diverse treatment options to adequately respond to the patients' needs. In the last 20 years, novel pathways have been investigated that were beyond the scope of histamine. Although most did not result in a molecule available on the Canadian market, it is interesting and important as health care providers to stay up to date with new neuronal pathways involved in itch transmission and potential new therapeutic options. In this review, we will discuss pathways targeted in new topical treatments such as antagonist of proteinase-activated receptor-2, the endocannabinoid system, neurotrophins and tropomyosin-related kinase A receptor, the transient receptor potential-vanilloid or transient receptor potential-melastatine ion channels. New systemic therapies are now focusing on antagonizing the neurokinin receptor, modulating the opioidergic system, or targeting itch cytokines such as interleukin-31.
- Role of Keratinocytes in Sensitive Skin. [Review]
- FMFront Med (Lausanne) 2019; 6:108
- Sensitive skin is a clinical syndrome defined by the occurrence of unpleasant sensations such as burning, stinging, tingling, pricking, or itching in response to various normally innocuous physical, …
Sensitive skin is a clinical syndrome defined by the occurrence of unpleasant sensations such as burning, stinging, tingling, pricking, or itching in response to various normally innocuous physical, chemical, and thermal stimuli. These particular symptoms have led the consideration of a potential dysfunction of the intra-epidermal nerve fibers (IENF) that are responsible for pain, temperature, and itch perception. This neuronal hypothesis has just been reinforced by recent studies suggesting that sensitive skin could become assimilated to small fiber neuropathy. Meanwhile, the involvement of keratinocytes, the pre-dominant epidermal cell type, has so far mainly been considered because of their role in the epidermal barrier. However, keratinocytes also express diverse sensory receptors present on sensory neurons, such as receptors of the transient receptor potential (TRP) family, including Transient Receptor Potential Vallinoid 1 (TRPV1), one of the main transducers of painful heat which is also involved in itch transduction, and Transient Receptor Potential Vallinoid 4 (TRPV4) which is depicted as a heat sensor. While TRPV1 and TRPV4 are expressed both by sensory neurons and keratinocytes, it has recently been demonstrated that the specific and selective activation of TRPV1 on keratinocytes is sufficient to induce pain. Similarly, the targeted activation of keratinocyte-expressed TRPV4 elicits itch and the resulting scratching behavior. So, contrary to classical conception, the IENF are not the exclusive transducers of pain and itch. In light of these recent advances, this review proposes to consider the putative role of epidermal keratinocytes in the generation of the unpleasant sensations characteristic of sensitive skin syndrome.
- Cutaneous nociception: Role of keratinocytes. [Journal Article]
- EDExp Dermatol 2019 May 24
- Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra-epidermal nerve endings were classically considered as the exclusive transducers…
Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra-epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.
- Comparison of Characteristics of Neuropathic and Non-neuropathic Pruritus to Develop a Tool for the Diagnosis of Neuropathic Pruritus: The NP5. [Journal Article]
- FMFront Med (Lausanne) 2019; 6:79
- The diagnosis of neuropathic pruritus (NP) may be difficult. The aim of this study was to compare the characteristics of both neuropathic pruritus and non-neuropathic pruritus (NNP) in order to elabo…
The diagnosis of neuropathic pruritus (NP) may be difficult. The aim of this study was to compare the characteristics of both neuropathic pruritus and non-neuropathic pruritus (NNP) in order to elaborate a tool to help the diagnosis of NP without clinical examination. One hundred and seven patients were included: Fifty three in the NP group and Fifty four in the NNP group. In multiple regression, presence of twinges, absence of burning, worsening with activity, no worsening with stress, and relief with cold ambient temperature were independent factors that were associated with NP. A score of two criteria out of five was optimal to discriminate NP from NNP with a sensitivity of 76% and a specificity of 77%. Alloknesis, hyperknesis, or the ice cube test were not included because their evaluation is based on clinical examination. Future high-powered studies are needed to confirm the results of the present study.
- Multi-target design strategies for the improved treatment of Alzheimer's disease. [Review]
- EJEur J Med Chem 2019 Aug 15; 176:228-247
- Alzheimer's disease (AD) is a multifactorial syndrome resulting in profound misery and poses a substantial burden on human health, economy, and society throughout the world. Based on the numerous AD-…
Alzheimer's disease (AD) is a multifactorial syndrome resulting in profound misery and poses a substantial burden on human health, economy, and society throughout the world. Based on the numerous AD-related targets in the disease network, multi-target design strategy is a crucial direction to seek for enhanced therapy, and multi-target drugs have the ability to regulate more targets than single-target drugs, affecting the disease network with more potency. Herein, we highlight nine major targets associated with AD, which are acetylcholine esterase (AChE), beta-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE-1), glycogen synthase kinase 3 beta (GSK-3β), monoamine oxidases (MAOs), metal ions in the brain, N-methyl-D-aspartate (NMDA) receptor, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H3 receptor), and phosphodiesterases (PDEs), and their respective relationship to the disease network. Furthermore, eleven multi-target design strategies classified by the involvement of AChE and related promising compounds for improved therapy of AD in recent years are described based on the nine major targets.
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- Hemotoxic Snakebite Presenting with Bilateral Blindness Due to Ischemic Occipital Infarcts. [Case Reports]
- IJIndian J Crit Care Med 2019; 23(2):99-101
- Cerebrovascular complications are rare following a Viperidae snake envenomation, let alone ischemic ones. This catastrophic hemorrhaging cascade is widely known to cause a wide array of manifestation…
Cerebrovascular complications are rare following a Viperidae snake envenomation, let alone ischemic ones. This catastrophic hemorrhaging cascade is widely known to cause a wide array of manifestations. Its manifestations can range from skin bleeds to fatal intracranial or organ hemorrhages. Our patient had cortical blindness secondary to an ischemic occipital infarct following a hemotoxic snakebite - a seemingly distinct oxymoron. The physician should be mindful of the fact that a hemotoxic snakebite can deceptively bring in ischemic attacks as well. Toxic vasculitis, thrombotic angiopathies, widespread vasospasm and endothelial damage are believed to shoulder a part of the disease process that can bring about tissue ischemia.