To see the other types of publications on this topic, follow the link: NOS inhibition.
Books on the topic 'NOS inhibition'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 books for your research on the topic 'NOS inhibition.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse books on a wide variety of disciplines and organise your bibliography correctly.
1
McCarty, Megan, and Steven Karau. Social Inhibition. Edited by Stephen G. Harkins, Kipling D. Williams, and Jerry Burger. Oxford University Press, 2016. http://dx.doi.org/10.1093/oxfordhb/9780199859870.013.9.
Full textAbstract:
Social inhibition is the tendency for behaviors that are exhibited when one is alone to be minimized in the presence of others. Despite the long tradition of research investigating the effects of social presence on behavior, research on social inhibition does not constitute a cohesive literature. This chapter integrates social inhibition research from different traditions, focusing on helping behaviors, emotional expression, and behaviors that elicit social disapproval. We discuss moderators and processes that explain when and why social inhibition occurs: arousal, ambiguity, pluralistic ignorance, diffusion of responsibility, feelings of capability, evaluation apprehension, and confusion of responsibility. Key distinctions between social inhibition and related concepts are presented, helping to establish social inhibition as a central social influence concept. We conclude with an analysis of why social inhibition research has not formed a cohesive literature, and we hope that our review of social inhibition facilitates the integration of future research on the topic.
2
Depa, Larisse, Larissa Depa, Crhisllane Vasconcelos, Vagner Fonseca, and Diego Frias. Estudo do uso de códons nos vírus da Dengue, Zika e Chikungunya com foco em terapia por inibição seletiva de tRNAs contra arboviroses. Edited by Diego Mariano. Alfahelix, 2021. http://dx.doi.org/10.51780/978-6-5992753-3-3.
Full textAbstract:
O vírus da dengue (DENV), o vírus da Zika (ZIKV) e o vírus da chikungunya (CHIKV) são espécies que apresentam relevância clínica para a saúde pública. Porém, ainda não existe um tratamento específico ou vacina disponível para esses arbovírus. Nesse contexto, é fundamental encontrar novos alvos terapêuticos que possam auxiliar estratégias e tratamentos mais eficientes. A metodologia de codon usage tem demonstrado bons resultados para encontrar alvos para terapias que visam inibidores de tradução. Este estudo buscou analisar o uso de códons e o equilíbrio entre a abundância relativa dos RNAs transportadores (tRNAs) para encontrar alvos terapêuticos que irão estimular novas alternativas de tratamento para infecções causadas pelos DENV, ZIKV e CHIKV. Para tanto, foi replicada uma estratégia computacional, assumindo uma terapia hipotética de inibição seletiva de tRNA (Selective Transport RNA Inhibition Therapy - STRIT), onde foi estabelecido um índice de potencial terapêutico (T-score) para encontrar potenciais espécies de tRNA que poderiam ser inibidas seletivamente para atenuar a replicação viral na célula hospedeira. Foram identificados os cinco códons com maior frequência relativa vírus/hospedeiro (mais relevantes para o vírus) nas seis espécies de arbovírus, notando que todos terminam com purinas A ou G. Os códons GGA (Glicina), AGA (Arginina) e ATA (Isoleucina) são relevantes em todos os flavivirus (ZIKV, DENV-1, DENV-2, DENV-3, DENV-4), mas não no alphavirus CHIKV, onde os códons ACG (Treonina) e CCG (Prolina) são os mais relevantes. Posteriormente, selecionando os cinco códons com maiores T-score nas seis espécies virais (30 códons em total) encontramos apenas 11 códons diferentes, todos terminados com A ou G. Agrupados segundo o nucleotídeo na primeira posição do códon estes 11 códons são: (AGA, ACA, ATA, ACG), (GGA, GCA, GTA, GCG), (CTA, CCG) e (TGG). No agrupamento, notamos outro fato intrigante: que 10 dos 11 códons mais bem ranqueados por T-score, terminam com GA, CA, TA ou CG. Nosso método identificou as espécies de tRNA (através da identificação do códon cognato com maior T-score), cuja inibição funcional por qualquer método específico a anticódon, poderia ter potenciais efeitos terapêuticos em células infectadas pelo vírus da Dengue, Zika e Chikungunya causando a inibição da tradução das proteínas do vírus sem ter um efeito deletério na sobrevivência das células hospedeiras durante o período da infeção. A predominância absoluta dos nucleotídeos A e G na terceira posição dos 11 códons com maior T-score, que por sua vez indica uma preferência dos arbovírus por 11 espécies de tRNA com C ou T na primeira posição do anticódon, abre um novo espaço de pesquisa na interação vírus-hospedeiro.
4
Howardell, Maynard J. Cox-2 Inhibitor Research. Nova Science Publishers, Incorporated, 2006.
Find full text
5
Howardell, Maynard J. Trends in Cox-2 Inhibitor Research. Nova Science Publishers, 2006.
Find full text
6
Mease, Philip. Biologic treatments for psoriatic arthritis apart from TNF inhibition. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198737582.003.0030.
Full textAbstract:
Psoriatic arthritis (PsA) is an immunologically mediated inflammatory disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis. Prior to the introduction of targeted biologic medications, such as TNF inhibitors, the ability to control disease activity was limited, with only modest effects noted with traditional oral medications such as methotrexate and sulfasalazine. The introduction of TNF inhibitors substantially changed the outlook of PsA patients, yielding significant response in all relevant clinical domains and demonstrating the ability to inhibit progressive structural damage of joints. However, not all patients responded to these agents and many patients displayed initial response which waned over time, partly due to immunogenicity (development of antibodies which blocked full therapeutic effect of the biologic protein), or because of tolerability and side effect issues. Thus, it has been important to develop new medicines which target other key cytokines and immunologic pathways. Several medicines with a different mechanism of action have been approved or are in development for the treatment of PsA. Ustekinumab inhibits both IL12 and IL23 and thus is felt to work in both the TH1 and TH7 pathways of inflammation. The oral medicine apremilast inhibits phosphodiesterase 4, thus modulating the cyclic AMP pathway in immunologic cells, yielding an anti-inflammatory effect. Both of these medicines have been approved for the treatment of PsA as well as psoriasis. An emerging group of therapies, the IL17 inhibitors, has demonstrated significant effectiveness in psoriasis and PsA and one of these, Secukinumab, has been approved for psoriasis, PsA, and AS. Other medicines in development include the co-stimulatory blockade agent, abatacept, oral Janus Kinase (JAK) inhibitors, and an emerging group of therapies which inhibit IL23. As modulators of immune cell function, these agents have the potential to increase risk for infection, as well as other side effects. These must be discussed with the patient and considered when determining overall risk benefit analysis regarding their use. The emergence of medicines with a different mechanism of action than TNF inhibition has broadened and strengthened our ability to effectively treat PsA.
7
Levi, Marcel, and Marcus J. Schultz. Disseminated intravascular coagulation in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0270.
Full textAbstract:
Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. In patients with DIC, a variety of altered coagulation parameters may be detectable, such as thrombocytopenia, prolonged global coagulation times, reduced levels of coagulation inhibitors, or high levels of fibrin split products. There is not a single test, however, that is sufficiently accurate to establish or reject a diagnosis of DIC. Nevertheless, a combination of widely available tests may be helpful in making the diagnosis of DIC and can also be helpful in guiding the selection of DIC patients that require specific, often expensive, interventions in the coagulation system. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways.
8
Hodges, John R. Testing Cognitive Function at the Bedside. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198749189.003.0005.
Full textAbstract:
This chapter explores the second component of assessment in patients with suspected cognitive dysfunction: testing cognitive function at the bedside. The first part of the examination should assess distributed cognitive functions, notably orientation and attention, episodic and semantic memory, and frontal executive function (initiation in the form of verbal fluency, abstraction, response inhibition, and set shifting); deficits in these indicate damage to particular brain systems, but not to focal areas of one hemisphere. The second part of the assessment deals with localized functions, divided into those associated with the dominant (i.e. the left side, in right-handers) and non-dominant hemispheres. The former relates largely to tests of spoken language with supplementary tests of reading, writing, calculation, and praxis when applicable. Testing right hemisphere function focuses on neglect (personal and extrapersonal), visuospatial and constructional abilities, and the agnosias including object and face agnosia.
9
Purdon, Christine, and C. Psych. Pathological Responsibility, Thought-Action Fusion, and Thought Control in OCD. Edited by Christopher Pittenger. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190228163.003.0018.
Full textAbstract:
Leading models of obsessive-compulsive disorder (OCD) implicate overvalued beliefs about responsibility, beliefs about the relationship of thoughts to external events and morality (thought-action fusion), and thought control as key factors in the development and the persistence of the disorder. This chapter provides an overview of these three factors and presents case examples, empirical support, and clinical implications. Considerable empirical research indicates that people with OCD tend to endorse beliefs reflecting an overvalued responsibility and thought-action fusion (TAF). However, it is also clear that these beliefs, particularly TAF beliefs, are not unique to OCD. It has been proposed that attempts at thought suppression ironically lead to an increase in thought frequency; research has generally not yielded support for such an effect, nor for response inhibition deficits. However, there is converging evidence that suppression may have insidious effects on the appraisal of thought recurrences and mood state. Clinical implications are discussed.
10
Hogan, Patrick Colm. Gender and Regulatory Regimes. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190857790.003.0006.
Full textAbstract:
The fifth chapter continues the focus on regulatory regimes, now turning to gender and taking up ideology and socialization rather than coercion. This chapter first considers some short stories by Tagore. Specifically, it examines the role of humiliation in the inhibition of boys’ empathic response, especially sensitivity about attachment needs. From here, the chapter turns to Woolf’s Orlando. In this novel, Woolf presents a situationist account of gender regulation. Orlando’s apparently masculine or feminine behaviors are provoked by such seemingly trivial situations as the nature of his/her clothing. Woolf nuances the situationist account by showing that some forms of situated behavior, as well as thought and feeling, are likely to become habitual through repetition. In short, it is not differences in minds that produce differences in behaviors, which in turn create social situations. Rather, differences in social situations produce differences in behaviors, leading to differences in thoughts and feelings.
11
Brandeis, Daniel, Sandra K. Loo, Grainne McLoughlin, Hartmut Heinrich, and Tobias Banaschewski. Neurophysiology. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198739258.003.0009.
Full textAbstract:
Neurophysiology allows us to understand and modulate the neural mechanisms in ADHD with high time- and/or frequency-resolution. These non-invasive methods include electroencephalographic recordings at rest and during tasks, with spontaneous and event-related oscillations and potentials tracking covert processing and transcranial neuromodulation through magnetic or electric fields. The findings indicate consistent cognitive and neural deficits in ADHD related to impaired attention and deficient inhibition. Advanced signal processing and source imaging methods often converge with other imaging approaches. Neurophysiological findings also reveal considerable heterogeneity in ADHD regarding cognitive, affective, and genetic subtypes. This illustrates the importance of dimensional approaches and of pathophysiological mechanisms partly shared with other disorders. Although several potential neurophysiological markers of ADHD have been considered, a clinical use for individual diagnostics and classification is not supported to date. More research should clarify the clinical potential of multivariate multimodal classification and prediction of treatment outcome to advance individualized treatment.
12
Healey, John H., and David McKeown. Orthopaedic surgery in the palliation of cancer. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199656097.003.0125.
Full textAbstract:
Metastatic spread of cancer to bone is frequent and causes pain, disability, and functional limitation. New understanding of the homing method of cancer cells to bone and the mechanism of cancer production of pain raise possible new treatment strategies. Non-surgical treatments such as chemotherapy and hormone therapy are effective in early disease. Bisphosphonates and inhibition of osteoprotegerin prevent progression of bone lesions and avoid pain, radiation, and surgery. Radiotherapy arrests disease and relieves pain in many cases. Surgery is needed when the bone is weak or fractured. It effectively relieves pain and preserves function. It usually requires replacing or bypassing the deficient bone with site-specific reconstructive surgery. Surgery should be selected based on projections of patient survival. New tools to make these projections have been validated and are now available. New targeted drug therapies appear to be changing metastatic bone disease into a more chronic condition. This will alter the management of local disease in many histological subtypes of metastatic cancers.
13
D’Mello, Ajay. Mitochondrial Disease. Edited by Kirk Lalwani, Ira Todd Cohen, Ellen Y. Choi, and Vidya T. Raman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190685157.003.0047.
Full textAbstract:
Mitochondrial disease is now considered to be an important cause for a diverse range of neurological, muscular, cardiac and endocrine disorders. Initially thought to be a rare group of disorders, it is now increasingly common for children with mitochondrial disease to present for a surgical procedure. While the mitochondrial respiratory chain is the essential finally common pathway for aerobic metabolism, mitochondria also play a role in a several important cellular processes. A variety of anesthetic techniques have been successfully used for this group of patients. However, the possibility of complications due to inhibition of mitochondrial function by anesthetic agents and surgical stress is a worry for the physician managing these patients. Anesthetic management focuses on disease symptoms at presentation, maintaining normoglycemia, while preventing further metabolic stress and complications that worsen lactic acidosis.
14
James, David. Decentring Englishness. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198749394.003.0027.
Full textAbstract:
This chapter asks if there is something about the displacement of national identity that correlates with the formal development of the ‘English Novel’, even though that designation is now considered untenable, if not unusable. Reservations about tracing correlations, let alone compatibilities, between the persistence of Englishness and the prose of novelists whose job might be to decentre it, are so consolidated in literary studies that the cautions hardly need rehearsing. Yet the chapter considers how we might approach writers whose self-categorization defies criticism’s prevailing inhibitions. And even when we do spot such contradictions, the chapter considers whether we can arbitrate, textually or biographically, in discrepancies between ethnic and aesthetic realms. In doing so, this chapter explores the ‘fairy tale’ of Englishness and what it might mean for our historical understanding of contemporary fiction.
15
Majid, Adrian, and Bruce L. Gilliam. Future Antiretrovirals, Immune-Based Strategies, and Therapeutic Vaccines. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0023.
Full textAbstract:
Highly active antiretroviral therapy remains the mainstay of treatment for patients chronically infected with HIV. Novel drugs, both within existing classes and new ones, are in various stages of development and testing. New medications within existing classes of antiretroviral agents are in clinical trials and will likely offer activity against resistant HIV-1 strains and provide alternatives for combination pill therapy. Novel therapeutics including oral attachment inhibitors and monoclonal antibody treatments continue to show efficacy against HIV-1 and progress in clinical trials. Tenofovir alafenamide is a prodrug that produces higher intracellular levels of tenofovir diphosphate with likely less renal and bone toxicity. Among traditional classes of HIV treatment, both doravirine (a non-nucleoside reverse transcriptase inhibitor) and cabotegravir (an integrase strand inhibitor) are newer agents with activity against resistant virus. Maturation inhibitors are a new class of treatment that block protease cleavage, leading to the release of an immature virion.
16
Chirimuuta, Mazviita. The Development and Application of Efficient Coding Explanation in Neuroscience. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198777946.003.0009.
Full textAbstract:
In the philosophy of neuroscience, much attention has been paid to mechanistic causal explanations, both in terms of their theoretical virtues, and their application in potential therapeutic interventions. Non-mechanistic, non-causal explanatory models, it is often assumed, would have no role to play in any practical endeavors. This assumption ignores the fact that many of the non-mechanistic explanatory models which have been successfully employed in neuroscience have their origins in engineering and applied sciences, and are central to many new neuro-technologies. This chapter examines the development of explanations of lateral inhibition in the early visual system as implementing an efficient code for converting photoreceptor input into a data-compressed output from the eye to the brain. Two applications of the efficient coding approach are considered: in streamlining the vast datasets of current neuroscience by offering unifying principles, and in building artificial systems that replicate vision and other cognitive functions.
17
Beiner, Guy. Post-Forgetting. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198749356.003.0008.
Full textAbstract:
Popular commemoration of previously forbidden memories seems to signal the end of social forgetting. Though this is not necessarily the final word. The bicentenary of 1798 coincided with the signing of the Good Friday Agreement, which promised to bring to Northern Ireland a new ‘parity of esteem’, accommodating traditions that had hitherto been forbidden. The wide range of commemorative activities through which the legacy of the United Irishmen has been publicly celebrated at a local and provincial level since 1998 gives the impression that all inhibitions about speaking of ‘Ninety-Eight’ have been overcome. Yet, on the background of continuing sectarian tensions in post-conflict Northern Ireland, there are indications that social forgetting has not been entirely eradicated.
18
Figueiredo, Camille, and Georg Schett. Assessment of joint and bone structure in PsA patients: Using high-resolution computed tomography. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198737582.003.0019.
Full textAbstract:
Psoriatic arthritis (PsA) is associated with a distinct pattern of bone pathology, which influences the clinical picture of the disease. High-resolution computed tomography (CT) has contributed to understanding structural bone changes in PsA. Periarticular bone erosions in PsA are characterized by periosteal responses around the cortical break, distinguishing them from bone erosions in rheumatoid arthritis. Furthermore, a large number of enthesophytes can be found in CT studies of joints of PsA patients and in psoriasis patients without clinical arthritis. This latter observation supports the idea that articular changes start in psoriasis before joint disease commences. Moreover, enthesophytes are not influenced by methotrexate treatment and tumour necrosis factor inhibition. Finally, studies of systemic bone loss by high-resolution CT revealed significant alterations of the bone architecture in PsA but not in patients with skin disease only. In summary, CT has made valuable contributions in understanding the structural bone changes in PsA.
19
Hallett, Mark, and Alfredo Berardelli. Movement Disorders. Edited by Charles M. Epstein, Eric M. Wassermann, and Ulf Ziemann. Oxford University Press, 2012. http://dx.doi.org/10.1093/oxfordhb/9780198568926.013.0044.
Full textAbstract:
This article focuses on the potential therapeutic uses of transcranial magnetic stimulation (TMS) in movement disorders. The brain can be stimulated with low levels of direct electrical current, called direct current polarization (tDCS). High-frequency repetitive TMS might increase brain excitability and be used for therapy in Parkinson's disease. Single sessions with TMS, however, have not proven to be very effective. Treatment with tDCS has been performed in some open studies with some success, but these results need confirmation. Physiological findings in dystonia reveal a decrease in intracortical inhibition. There have been a few studies of patients with Tourette's syndrome with mixed results. To date, clinical results with TMS in movement disorders have been mixed, and more work will be needed to clarify the potential clinical role of TMS.
20
Gilbert, Paul, and Jennifer S. Mascaro. Compassion Fears, Blocks and Resistances. Edited by Emma M. Seppälä, Emiliana Simon-Thomas, Stephanie L. Brown, Monica C. Worline, C. Daryl Cameron, and James R. Doty. Oxford University Press, 2017. http://dx.doi.org/10.1093/oxfordhb/9780190464684.013.29.
Full textAbstract:
While there is increasing research on the benefits and facilitators of compassion, as with all motives, there are inhibitors. This chapter will not cover the benefits of compassion, explored in other chapters, but instead considers its inhibitors: the fears, blocks, and resistances (FBRs) to compassion and their evolutionary and psychosocial origins. We begin with an explication of a model for compassion, and show how compassion rests on discrete components and competencies that can be differentially inhibited. Next, we utilize Ernst Mayr’s (1961) classic heuristic to understand compassion inhibition; namely, the “ultimate” and “proximate” analysis. We conclude with an exploration of the antidotes to these inhibitors. Greater research into the nature of compassion inhibitors and insights on how to address them could increase the use of compassion in different domains of life.
21
Georgeson, Mark. The Graph-Paper Effect. Oxford University Press, 2017. http://dx.doi.org/10.1093/acprof:oso/9780199794607.003.0107.
Full textAbstract:
Most visual illusions involve distorted or altered perception of objects or events or misinterpretation of image information. The discrepancy between what we experience and what is physically present in the world or in the retinal image can be large, surprising, and dramatic. It is much rarer to see things that simply are not there at all. Repetitive stimuli, such as grating patterns or flickering lights, can induce perception of a range of illusory geometric patterns, forms, and movements—during or after exposure to the inducing stimulus. This chapter describes one such illusory phenomenon—the graph-paper effect—a striking illusion of moving, oriented lines and edges; links it to a family of related effects; and offers a general theory for these effects in terms of neural inhibition and disinhibition at the level of the visual cortex.
22
Speer, Thimoteus, and Danilo Fliser. Abnormal endothelial vasomotor and secretory function. Edited by David J. Goldsmith. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0113.
Full textAbstract:
The endothelium plays a crucial role in the maintenance of vascular integrity and function. Nitric oxide produced by endothelial cells is a key player, inducing relaxation of vascular smooth muscle cells, inhibition of vascular inflammation, and prevention of coagulatory activation. Chronic kidney disease (CKD) is characterized by deterioration of different protective endothelial properties, collectively described as endothelial dysfunction. Several factors such as methylarginines, modified lipoproteins, and other substances that accumulate may be involved in the pathogenesis of endothelial dysfunction of CKD. Endothelial dysfunction is suggested to be the first critical step in the initiation of atherosclerosis. Clinical assessment of endothelial function may become important in recognition of patients with increased cardiovascular risk. Beside several invasive and non-invasive methods to assess endothelial function in vivo, measurement of circulating (bio)markers may be useful for the evaluation of endothelial dysfunction.
23
Carpenter, Gregory, and Meenal Patil. Gender Differences in Pain. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190217518.003.0005.
Full textAbstract:
Epidemiologic and clinical findings demonstrate that women are at increased risk for chronic pain, experience greater pain-related distress, and show heightened sensitivity for pain compared to men. There are differences in analgesic responses to pain and to both opioid and non-opioid medications as well as for endogenous analgesic processes. Many stress-related disorders, such as fibromyalgia and chronic pain, are more prevalent in women. Studies of experimentally induced pain show that women exhibit greater pain sensitivity, enhanced pain facilitation, and reduced pain inhibition compared to men. Mechanisms that implicated in the underlying sex differences include biological involvement of estrogen and progesterone versus testosterone. Sex-related differences in pain may also reflect differences in the endogenous opioid system. Other mechanisms include steroid action differences in adulthood, modulation of various biological systems such as the cardiovascular and inflammatory pathways, and sociocultural differences
24
Calabrò, Fabio, and Cora N. Sternberg. Treatment of metastatic bladder cancer. Edited by James W. F. Catto. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0079.
Full textAbstract:
Although bladder cancer is considered a chemosensitive malignancy, the prognosis of patients with metastatic disease is poor, with a median survival of approximately 12–14 months in good prognosis patients and with cure in only a minority. The addition of new drugs to the standard cisplatin-based regimens has not improved these outcomes. In this chapter, we highlight the role of chemotherapy and the impact of the new targeted agents in the treatment of metastatic bladder carcinoma. A better understanding of the underlying biology and the molecular patterns of urothelial bladder cancer has led to clinical investigation of several therapeutic targets. To date, these agents have yet to demonstrate an improvement in overall survival. Urothelial cancer is extremely sensitive to checkpoint inhibition with both anti PD-1 and anti PDL1 antibodies. The future seems brighter with the advent of these new therapies.
25
Bird, Mark F., and David G. Lambert. Deorphanization of ORL-1/LC132 by reverse pharmacology in two landmark studies. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0026.
Full textAbstract:
Deorphanization of ORL-1/LC132 in 1995 by reverse pharmacology in two simultaneously published landmark studies added a new member to the opioid family of G-protein coupled receptors. Meunier and Reinscheid used cells expressing recombinant ORL-1 (human) or LC132 (rat) and the presumed intracellular inhibition of cyclic AMP formation to ‘fish’ for endogenous peptide ligands in rat whole-brain and pig hypothalamic extracts. Both studies reported the isolation of a 17-amino-acid peptide, which was named nociceptin and orphanin FQ by the two authors, respectively. The behaviour of the isolated peptide was a complete surprise, as a general hyperalgesia was observed when the peptide was administered at supraspinal sites. We now know that this peptide has, in fact, anti-opioid action, particularly in the medulla. The endogenous peptide exerts a multitude of effects both in the nervous system and, unlike classical opioids, has efficacy in neuropathic pain.
26
Marchand, Serge. The milestone effect of DNIC in our understanding of pain. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0039.
Full textAbstract:
While thousands of articles are published each year on pain, only a few have such a major impact on the understanding of pain mechanisms as the landmark paper discussed in this chapter; published by Le Bars and colleagues in 1979, it introduced the concept of diffuse noxious inhibitory control (DNIC; also called diffuse noxious inhibition) mechanisms. Although this work is more than three decades old, it still has a major influence on both the understanding of pain mechanisms and the development of clinical approaches. It is known that apparently similar pain may be caused by different mechanisms: one may be caused by amplified excitatory mechanisms while the other may be related to a deficit of endogenous pain modulation, such as DNIC or conditioned pain modulation (or CPM); these will not respond to the same treatment. The work by Le Bars and colleagues provided a new understanding of mechanisms underlying pain.
27
Walker, Matthew C., and Robin S. B. Williams. Identifying the Molecular Mechanism of the Medium Chain Triglyceride (Ketogenic) Diet. Edited by Dominic P. D’Agostino. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190497996.003.0033.
Full textAbstract:
The medium chain triglyceride (MCT) ketogenic diet provides a highly effective and commonly used approach for treating drug-resistant epilepsy. It is associated with elevated levels of two MCT-derived fatty acids, decanoioc and octanoic acids. Researchers have identified a role for decanoic acid and a range of novel related chemicals in seizure control in multiple acute in vitro and in vivo models. A principal mechanism of decanoic acid is direct inhibition of AMPA receptors, key excitatory neurotransmitter receptors widely recognized as a target for seizure control. These data suggest a therapeutic mechanism of the MCT ketogenic diet through a direct fatty acid–dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. The diet should be termed the MCT diet, as the consequent ketosis may not be necessary for seizure control.
28
Kortgen, Andreas, and Michael Bauer. The effect of acute hepatic failure on drug handling in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0197.
Full textAbstract:
Impaired hepatic function is a common event in intensive care unit patients and as the liver plays a central role in drug metabolism and excretion this may lead to profound changes in pharmacokinetics. Underlying mechanisms are altered enzyme function of phase I and phase II metabolism, altered transporter protein function together with cholestasis and hepatic perfusion disorders. Moreover, multidrug therapy may lead to induction and inhibition of these enzymes and transporter proteins. In addition, changes in plasma protein binding and volumes of distribution of drugs are common. Altogether, these changes may not only lead to sometimes unpredictable plasma levels of xenobiotics, but also to drug-induced liver injury when hepatocellular accumulation of noxious substances occurs. Concomitant renal dysfunction may further complicate this situation. Pharmacodynamic alterations might also occur. In conclusion, the clinician must carefully evaluate medication given to patients with hepatic failure. Therapeutic drug monitoring should be performed wherever available to guide therapy.
29
Guastella, Adam J., Alice Norton, Gail A. Alvares, and Yun Ju Christine Song. Current and Experimental Treatments for Anxiety Disorders. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0040.
Full textAbstract:
There are currently a range of treatments available for anxiety disorders, including pharmacological and behavior-based therapies. The most widely used medications, for which there is considerable evidence of efficacy across a range of anxiety disorders, are the serotonin-selective reuptake inhibitor antidepressants. Benzodiazepines are also widely prescribed and show efficacy for acute anxiety, but their use in the treatment of chronic anxiety syndromes is more problematic. Many patients are not adequately covered by the available range of medications, which is driving interest in potentially new pharmacological approaches. The best established non-pharmacological treatment of anxiety is cognitive behavioral therapy and several related behavioral approaches, which have been shown to be efficacious in a range of anxiety disorders. One of these related approaches is called cognitive bias modification, which aims to alter an individual’s responses to anxiety-provoking stimuli.
30
van Dorp, Eveline L. A., Douglas Eleveld, Erik Olofsen, and Jaap Vuyk. Drug distribution and elimination in anaesthetic practice. Edited by Michel M. R. F. Struys. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0012.
Full textAbstract:
An understanding of pharmacokinetics is vital for the practice of anaesthesia. Drugs are, after administration, distributed throughout the body to the effect site (mostly the brain) to exert their effects. This can be influenced by differences in protein binding, systemic blood flow, and concomitant medication. Elimination of drugs from the body is through two main routes: either unchanged through the kidneys or through metabolism by the liver (and consecutive excretion through the kidneys). This process depends on the amount of hepatic blood flow and the amount of hepatic extraction. This in turn depends on the amount of protein binding and the intrinsic hepatic clearance. The cytochrome P450 enzyme family also plays an important role in drug elimination. Individual differences in enzyme activity can lead to differences in drug effect and clearances. Changes in enzyme activity by enzyme induction and inhibition can also be of influence on drug clearance. Compartmental, non-compartmental, and physiologically based models, and various statistical approaches to estimate these models, may be used to analyze the distribution and elimination of anaesthetic agents.
31
Meka, Eltion, and Stefano Bianchini, eds. The Challenges of Democratization and Reconciliation in the Post-Yugoslav Space. Nomos Verlagsgesellschaft mbH & Co. KG, 2020. http://dx.doi.org/10.5771/9783748921516.
Full textAbstract:
This book explores the challenges of democratization and reconciliation in the context of European integration in the post-Yugoslav region. Despite its academic and policy relevance, students and academics studying the region do not have a single source of reading material where they can learn about the challenges facing the region. This book aims to serve an array of college students and become a go-to source in studying the region. Adopting an interdisciplinary approach, the book provides readers with a comprehensive account of the various challenges inhibiting democratization and reconciliation. The chapters are written by authors from different disciplines, thus allowing readers to analyze the region from different perspectives.
32
Clark, Caroline, Jeffrey Cole, Christine Winter, and Geoffrey Grammer. Transcranial Magnetic Stimulation Treatment of Posttraumatic Stress Disorder. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190205959.003.0005.
Full textAbstract:
Symptoms of post-traumatic stress disorder (PTSD) often fail to resolve with psychotherapy, pharmacotherapy, or integrative medicine treatments. Given these limitations, there is a continued push to discover treatment methods utilizing novel mechanisms of action. Transcranial magnetic stimulation (TMS) offers a non-invasive and safe method of brain stimulation that modulates neuronal activity in a focal area to achieve excitation or inhibition, and may have utility for patients suffering from PTSD, although, to date, evidence of efficacy is limited. The TMS treatment can be varied to suit the needs of the patient by altering the selection of the specific treatment parameters, such as pulse frequency or stimulation intensity. The weight of evidence to date supports treatment of either the right dorsolateral prefrontal cortex or the medical prefrontal cortex. Coupling treatment with script based exposure therapies may also assist with potentiation of the extinction response. Ultimately, stimulation parameters may be related to secondary downstream effects, and thus current targets may indirectly reverse the underlying neuronal pathophysiology. Given that PTSD is a complex illness with a poorly understood pathophysiology, it often exists with other psychiatric comorbidities or TBI. As such, TMS could be an effective part of a comprehensive treatment program.
33
Tobon, Amalia Londono, and Hanna E. Stevens. Adolescents with SSRI-Resistant Depression. Edited by Ish P. Bhalla, Rajesh R. Tampi, Vinod H. Srihari, and Michael E. Hochman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190625085.003.0008.
Full textAbstract:
This chapter provides a summary of a landmark study in child and adolescent psychiatry addressing the common clinical experience of an adolescent that does not respond to initial antidepressant treatment. Should adolescents with selective serotonin reuptake inhibitor (SSRI) resistant depression be switched to another SSRI or to venlafaxine with or without cognitive behavioral therapy? Starting with that question, it describes the basics of the study, including funding, study locations, who was studied, how many patients, study design, study interventions, follow-up, endpoints, results, and criticism and limitations. This chapter also briefly reviews other relevant studies and information, discusses implications of the findings, and concludes with a relevant clinical case scenario and suggested management for the case.
34
Fayssoil, Abdallah, and Djillali Annane. Inotropic agents in critical illness. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0036.
Full textAbstract:
Inotropes are drugs commonly used in the intensive care unit. This class of agents includes a broad variety of molecules that improve cardiac index by increasing intracellular concentrations of cyclic AMP, or sensitivity to intracellular calcium, or by inhibiting the sodium/potassium pump. The main inotropic agents available are digoxin, catecholamines, and non-catecholergic drugs, e.g. phosphodiesterase inhibitors and levosimendan. In practice, dobutamine, a beta1 and beta2 agonist, is the inotrope of choice in patients with acute heart failure, or in patients with severe sepsis and evidence for left ventricle dysfunction. Levosimendan may be an alternative choice in patients with severe heart failure, particularly for those previously treated with beta-blockers. The main serious adverse events related to any inotrope are life-threatening arrhythmias.
35
Dilsizian, Vasken, Ines Valenta, and Thomas H. Schindler. Myocardial Viability Assessment. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199392094.003.0021.
Full textAbstract:
Heart failure may be a consequence of ischemic or non-ischemic cardiomyopathy. Etiologies for LV systolic dysfunction in ischemic cardiomyopathy include; 1) transmural scar, 2) nontransmural scar, 3) repetitive myocardial stunning, 4) hibernating myocardium, and 5) remodeled myocardium. The LV remodeling process, which is activated by the renin-angiotensin system (RAS), stimulates toxic catecholamine actions and matrix metalloproteinases, resulting in maladaptive cellular and molecular alterations5, with a final pathway to interstitial fibrosis. These responses to LV dysfunction and interstitial fibrosis lead to progressive worsening of LV function. Established treatment options for ischemic cardiomyopathy include medical therapy, revascularization, and cardiac transplantation. While there has been continuous progress in the medical treatment of heart failure with beta-blockers, angiotensin-converting enzyme (ACE) inhibition, angiotensin II type 1 receptor (AT1R) blockers, and aldosterone to beneficially influence morbidity and mortality, the 5-years mortality rate for heart failure patients remains as high as 50%. Revascularization procedures include percutaneous transluminal coronary artery interventions (PCI) including angioplasty and endovascular stent placement and coronary artery bypass grafting (CABG). Whereas patents with heart failure due to non-coronary etiologies may best benefit from medical therapy or heart transplantation, coronary revascularization has the potential to improve ventricular function, symptoms, and long term survival, in patients with heart failure symptoms due to CAD and ischemic cardiomyopathy.
36
Abhishek, Abhishek, and Michael Doherty. Placebo, nocebo, and contextual effects. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0027.
Full textAbstract:
Placebo effect is an example of ‘contextual’ effect and is the symptomatic improvement experienced by patients who have unknowingly received a placebo (inactive treatment) instead of an active drug. It occurs due to patient-specific factors such as expectation of improvement and is influenced by the context in which the treatment is delivered. Nocebo effect is the opposite of placebo effect and includes worsening of symptoms or incident adverse effects due to expectancy or negative contextual or practitioner influence. Placebo effect has been demonstrated in a range of musculoskeletal conditions, including osteoarthritis (OA), as well as other conditions such as Parkinson’s disease, irritable bowel syndrome, and asthma. In OA, the placebo effect is strongest for subjective outcomes like pain. In fact, the effect size (ES) of placebo analgesia in OA clinical trials (0.51) is clinically significant and higher than the ES (defined by the additional improvement above placebo) obtained from non-pharmacological (0.25) and pharmacological (0.39) treatments. A number of patient- and intervention-specific and contextual factors influence the magnitude of placebo-induced improvements. Placebo analgesia is real, not a ‘trick of the mind’, and results from central mechanisms that increase descending inhibition of pain. Contextual effects are an integral part of everyday clinical practice. While patient- and intervention-specific determinants cannot be changed easily, healthcare practitioners should optimize the physician-specific factors that enhance positive contextual response and minimize nocebo response. Such a strategy that will increase the overall improvement is particularly relevant for OA where there is no ‘cure’ and a predominance of negative beliefs.
37
Bueno, Héctor, and José A. Barrabés. Non-ST-segment elevation acute coronary syndromes. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0046.
Full textAbstract:
Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
38
Bueno, Héctor, and José A. Barrabés. Non-ST-segment elevation acute coronary syndromes. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199687039.003.0046_update_001.
Full textAbstract:
Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
39
Bueno, Héctor, and José A. Barrabés. Non-ST-segment elevation acute coronary syndromes. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199687039.003.0046_update_002.
Full textAbstract:
Non-ST-segment elevation acute coronary syndromes are life-threatening disorders, usually caused by acute coronary thrombosis and subsequent myocardial ischaemia, presenting without persistent ST-segment elevation in the initial electrocardiogram. According to the occurrence of myocardial necrosis, non-ST-segment elevation acute coronary syndromes are divided into non-ST-segment myocardial infarction or unstable angina. The management of non-ST-segment elevation acute coronary syndromes requires an early diagnosis and risk stratification, urgent hospitalization, monitoring, and medical treatment, including antithrombotic therapy with dual antiplatelet therapy (aspirin plus one P2Y12 inhibitor) and parenteral anticoagulation, anti-ischaemic treatment, and preventative therapies. After the initial medical therapy is established, an invasive strategy, consisting of coronary angiography with coronary revascularization (either percutaneous coronary intervention or coronary bypass graft surgery), as appropriate, should be decided. The timing of the invasive strategy should be adjusted, according to the patient’s risk. Given the high event rate of patients with non-ST-segment elevation acute coronary syndromes after hospital discharge, an aggressive long-term preventative therapy should be put in place to improve prognosis.
40
Camhy, Daniela G., ed. Enlightenment Today. Academia Verlag, 2020. http://dx.doi.org/10.5771/9783896658647.
Full textAbstract:
“Enlightenment is man's release from his self-incurred tutelage“, says Kant. And continues: „Tutelage is man's inability to make use of his understanding without direction from another.“ The question of enlightenment is not only relevant in Kant's time, but also today. Might the enlightened, responsible and autonomous subject be endangered? Where are the most inhibitions on the way to independent thinking? Are radicalization, emotions and irrationality taking the lead? Why debate on enlightenment today? The International Congress for the Philosophy of Children devoted itself to these questions. The complexity of the modern world, the variety of choices, the scientific progress, the emergence of numerous expert cultures, the complexity of the conditions present us with enormous challenges. So, how about education and enlightenment? With contributions by Rainer Enskat, Gideon Stiening, German Melikhov und Aleksey Melikhov, Kathrin Bouvot, Eva Marsal, Nicole Decostre, Evelina Ivanova, Johanna Hawken, Maja Soboleva, Rudolf Meer, Arie Kizel, Desiree Moodley, Gianluigi Segalerba, Arie Kizel und Dorit Kershner, Sofia Nikolidaki, Daniela G. Camhy, Hermann Maurer und Namik Delilovic, Carlos Francisco de Sousa Reis, Elsa Haraldsdóttir
41
Krauzlis, Richard J. Attentional Functions of the Superior Colliculus. Edited by Anna C. (Kia) Nobre and Sabine Kastner. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199675111.013.014.
Full textAbstract:
The superior colliculus (SC) plays an important role in both overt and covert attention. In primates, the SC is well known to be a central component of the motor pathways that orient the eyes and head to important objects in the environment. Accordingly, neurons in the SC show enhanced responses that will be the target of orienting movements, compared to stimuli that will be ignored. Single-neuron recordings in the SC have revealed a variety of attention-related effects, including changes in activity related to bottom-up and top-down attention, attention capture, and inhibition of return. These findings support the view of the SC as a priority map that represents the location of important objects in the visual environment. Manipulation of SC activity by electrical microstimulation and chemical inactivation shows that the SC is not simply a recipient of attention-related effects, but plays a causal role in these processes. In particular, activity in the SC plays a major role in the selection of targets for saccades, and also for pursuit eye movements and movements of the hand. Moreover, activity in the SC is important not only for the control of overt attention, but also plays a crucial role in covert attention—the processing of visual signals for perceptual judgements even in the absence of orienting movements. The mechanisms mediating the role of the SC in the control of covert attention are not yet known, but current models emphasize interactions between the SC and areas of the cerebral cortex.
42
Straub, Rainer H. Neuroendocrine system. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0022.
Full textAbstract:
Endocrine abnormalities are very common in patients with chronic autoimmune rheumatic diseases (CARDs) due to the systemic involvement of the central nervous system and endocrine glands. In recent years, the response of the endocrine (and also neuronal) system to peripheral inflammation has been linked to overall energy regulation of the diseased body and bioenergetics of immune cells. In CARDs, hormonal and neuronal pathways are outstandingly important in partitioning energy-rich fuels from muscle, brain, and fat tissue to the activated immune system. Neuroendocrine regulation of fuel allocation has been positively selected as an adaptive programme for transient serious, albeit non-life-threatening, inflammatory episodes. In CARDs, mistakenly, the adaptive programmes are used again but for a much longer time leading to systemic disease sequelae with endocrine (and also neuronal) abnormalities. The major endocrine alterations are depicted in the following list: mild activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, inadequate secretion of ACTH and cortisol relative to inflammation, loss of androgens, inhibition of the hypothalamic-pituitary-gonadal axis and fertility problems, high serum levels of oestrogens relative to androgens, fat deposits adjacent to inflamed tissue, increase of serum prolactin, and hyperinsulinaemia (and the metabolic syndrome). Neuroendocrine abnormalities are demonstrated using this framework that can explain many CARD-related endocrine disturbances. This chapter gives an overview on pathophysiology of neuroendocrine alterations in the context of energy regulation.
43
Straub, Rainer H. Neuroendocrine system. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0022_update_002.
Full textAbstract:
Endocrine abnormalities are very common in patients with chronic autoimmune rheumatic diseases (CARDs) due to the systemic involvement of the central nervous system and endocrine glands. In recent years, the response of the endocrine (and also neuronal) system to peripheral inflammation has been linked to overall energy regulation of the diseased body and bioenergetics of immune cells. In CARDs, hormonal and neuronal pathways are outstandingly important in partitioning energy-rich fuels from muscle, brain, and fat tissue to the activated immune system. Neuroendocrine regulation of fuel allocation has been positively selected as an adaptive programme for transient serious, albeit non-life-threatening, inflammatory episodes. In CARDs, mistakenly, the adaptive programmes are used again but for a much longer time leading to systemic disease sequelae with endocrine (and also neuronal) abnormalities. The major endocrine alterations are depicted in the following list: mild activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, inadequate secretion of ACTH and cortisol relative to inflammation, loss of androgens, inhibition of the hypothalamic-pituitary-gonadal axis and fertility problems, high serum levels of oestrogens relative to androgens, fat deposits adjacent to inflamed tissue, increase of serum prolactin, and hyperinsulinaemia (and the metabolic syndrome). Neuroendocrine abnormalities are demonstrated using this framework that can explain many CARD-related endocrine disturbances. This chapter gives an overview on pathophysiology of neuroendocrine alterations in the context of energy regulation.
44
Straub, Rainer H. Neuroendocrine system. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199642489.003.0022_update_003.
Full textAbstract:
Endocrine abnormalities are very common in patients with chronic autoimmune rheumatic diseases (CARDs) due to the systemic involvement of the central nervous system and endocrine glands. In recent years, the response of the endocrine (and also neuronal) system to peripheral inflammation has been linked to overall energy regulation of the diseased body and bioenergetics of immune cells. In CARDs, hormonal and neuronal pathways are outstandingly important in partitioning energy-rich fuels from muscle, brain, and fat tissue to the activated immune system. Neuroendocrine regulation of fuel allocation has been positively selected as an adaptive programme for transient serious, albeit non-life-threatening, inflammatory episodes. In CARDs, mistakenly, the adaptive programmes are used again but for a much longer time leading to systemic disease sequelae with endocrine (and also neuronal) abnormalities. The major endocrine alterations are depicted in the following list: mild activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, inadequate secretion of ACTH and cortisol relative to inflammation, loss of androgens, inhibition of the hypothalamic-pituitary-gonadal axis and fertility problems, high serum levels of oestrogens relative to androgens, fat deposits adjacent to inflamed tissue, increase of serum prolactin, and hyperinsulinaemia (and the metabolic syndrome). Neuroendocrine abnormalities are demonstrated using this framework that can explain many CARD-related endocrine disturbances. This chapter gives an overview on pathophysiology of neuroendocrine alterations in the context of energy regulation.
45
Piatkowski, Marcin. What Black Death was to Western Europe, Communism was to Central and Eastern Europe. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198789345.003.0004.
Full textAbstract:
I argue in this chapter that despite its ultimate social, economic, and moral bankruptcy, communism imposed on Poland after 1945 sowed the seeds of the country’s economic success after 1989. The old, feudal social structures were bulldozed to snap Poland out of growth-inhibiting extractive society equilibrium, creating a classless society, boosting social mobility, and securing good quality of education for all. Forced industrialization and unprecedented labour movements supported solid GDP growth rates in Poland until the 1960s, but low returns on investment, lack of technological progress, and external shocks caused declining growth rates in the 1970s, and economic stagnation in the 1980s. I conclude that the assumption that if Poland had returned to capitalism after 1945, it would have developed as quickly as the West, is simplistic. I show that a capitalist Poland would have faced significant challenges to growth, and convergence with the West would not have been guaranteed.
46
Bakir, Caner, and Günes Ertan, eds. Policy Analysis in Turkey. Policy Press, 2018. http://dx.doi.org/10.1332/policypress/9781447338956.001.0001.
Full textAbstract:
This book provides the first comprehensive overview of the state of policy analysis in Turkey. Policy analysis in Turkey, both as an academic inquiry and as a systematic practice in public and other policy-oriented organizations had been quite limited up until the 1990s. The book first examines the evolution of policy analysis in Turkish academia and public organizations followed by an in-depth review of the dominant modes of policy analysis performed by governmental and non-governmental actors. Throughout the chapters a special emphasis is given to structural constraints inhibiting the adoption of policy analytic approaches as well as the facilitating actors and forces such as international organizations. Overall, we challenge the caricatured image of policy making in Turkey as a uniform, strictly top-down hierarchical process that is solely shaped by politics and reveal the more complex decision-making mechanisms that vary significantly among policy-making actors.
47
Jani, Suni, Ryan Herringa, and Derek Hursey. Pharmacologic Treatment of Children with Trauma- and Stressor-Related Disorders. Edited by Frederick J. Stoddard, David M. Benedek, Mohammed R. Milad, and Robert J. Ursano. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190457136.003.0023.
Full textAbstract:
This chapter reviews the principles of psychopharmacological treatment for trauma and stressor-related disorders in children. It will discuss emerging psychopharmacological treatments and theories of trauma- and stress-related disorders (TSRDs) common to childhood, reactive attachment disorder, and disinhibited social engagement disorder. Although there is limited literature on the role of pharmacotherapy in treating TSRDs in children, it has been recognized that α- and β-adrenergic blocking agents, novel antipsychotic agents, non-selective serotonin reuptake inhibitor antidepressants such as tricyclic antidepressants, and mood-stabilizing agents may be effective for children based on several open clinical trials. These trials, as well as existing promising clinical trials, are discussed in this chapter. It also provides an in-depth review of factors such as potential side effects, medication interactions, and black box warnings as they specifically apply to the pediatric population.
48
Phillips, Katharine A. Insight and Delusional Beliefs in Body Dysmorphic Disorder. Edited by Katharine A. Phillips. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190254131.003.0009.
Full textAbstract:
This chapter discusses insight (“delusionality”) in body dysmorphic disorder (BDD). BDD beliefs span a broad range of insight, from good to absent insight (i.e., delusional beliefs). About 70% of patients have poor or absent insight. Early emerging clues suggest possible neurobiologic bases of poorer insight in BDD. BDD’s delusional form (characterized by the absence of insight) appears to be the same disorder as its nondelusional form rather than a separate psychotic disorder. Consistent with this, serotonin-reuptake inhibitor (SRI) monotherapy is efficacious for delusional BDD as well as nondelusional BDD. Neuroleptic (antipsychotic) monotherapy is not currently recommended for delusional BDD. Cognitive-behavioral therapy (CBT) appears efficacious for both delusional and nondelusional BDD, but research is needed to determine whether a somewhat modified approach may be helpful for delusional beliefs. Insight often improves with SRIs and CBT.
49
Lambert, David G. Mechanisms and determinants of anaesthetic drug action. Edited by Michel M. R. F. Struys. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0013.
Full textAbstract:
This chapter is broken into two main sections: a general description of the principles of ligand receptor interaction and a discussion of the main groups of ‘targets’; and explanation of some common pharmacological interactions in anaesthesia, critical care, and pain management. Agonists bind to and activate receptors while antagonists bind to receptors and block the effects of agonists. Antagonists can be competitive (most common) or non-competitive/irreversible. The main classes of drug target are enzymes, carriers, ion channels, and receptors with examples of anaesthetic relevance interacting with all classes. There are many examples in anaesthesia where multiple interacting drugs are co-administered—polypharmacology. To give an example: neuromuscular blockade. Rocuronium is a non-depolarizing neuromuscular blocker acting as a competitive antagonist at the nicotinic acetylcholine receptor. Rocuronium competes with endogenous acetylcholine to shift the concentration–response curve for contraction to the right. The degree of contractility is less for a given concentration of acetylcholine (agonist) in the presence of rocuronium. Using the same principle, the rightward shift can be compensated by increasing the amount of acetylcholine (as long as the amount of rocuronium presented to the receptor as an antagonist remains unchanged, its action can be overcome by increased agonist). Acetylcholine at the effect site is increased by acetylcholinesterase inhibition with neostigmine. One of the side-effects of neostigmine is that it acts as an indirect parasympathomimetic. In the cardiovascular system this would lead to muscarinic receptor-mediated bradycardia; these effects are routinely reversed by the competitive muscarinic antagonist glycopyrrolate.
50
Javanbakht, Arash, and Gina R. Poe. Behavioral Neuroscience of Circuits Involved in Arousal Regulation. Edited by Israel Liberzon and Kerry J. Ressler. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190215422.003.0007.
Full textAbstract:
This chapter evaluates the evidence that hyper-reactive noradrenergic responses during trauma contribute to hyperarousal symptoms in PTSD, including disturbances in sleep. Some genetic vulnerability for PTSD involves the adrenergic system, and a hyperactive central noradrenergic system might serve to over-consolidate and sustain the affective component of fear memories. Reduced moderation of noradrenergic reactions during low hormone phases of the menstrual cycle could also lead to increased susceptibility to PTSD. This chapter considers a mechanism by which hyperactivity in the noradrenergic system during sleep would impair REM sleep theta and non-REM sleep spindles in the limbic system, both of which are implicated in the consolidation of new safety memories, thereby compromising extinction recall and setting into motion a positive feedback loop in PTSD pathophysiology, involving hyperarousal, failure to integrate contextual information, and biased attention to threat. If so, novel pharmacotherapeutic interventions inhibiting the noradrenergic system during sensitive periods in sleep should be considered.