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Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems—whether traumatic, metabolic, or toxic—result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy.

Key Points Nociceptors can be activated and eventually sensitized by several pro-inflammatory mediators, including cytokines and chemokines. These mediators cause profound changes in sensory neurons, including mobilization of intracellular calcium, an increase in voltage- or ligand-gated channel expression or function, and alteration of the cellular transcriptional profile. The role of autoantibodies is increasingly being recognized in persistent pain states. Some autoantibodies trigger inflammation and have destructive effects within the sensory nervous system — for instance, neuromyelitis optica and Guillain–Barré syndrome. Some autoantibodies may alter the functional status of the somatosensory system, such as antibodies directed against voltage-gated potassium channel complexes. Nociceptors can affect vascular permeability and modulate the phenotype of immune cells through the release of neuropeptides (such as calcitonin gene-related peptide or substance P) or potentially via the other mediators that are readily released upon activation. Several studies suggest that the interactions between nociceptors and immune cells may have a role in the pathogenesis of several immune-mediated diseases, including arthritis, colitis and psoriasis, as well as upon infection. As a proof of concept, chemical disruption or genetic ablation of nociceptors has a drastic impact on the onset, severity and resolution of several pathological conditions in vivo . Similar conclusions have been suggested by clinical reports. Bidirectional signalling between nociceptors and immune cells protects the host from potential threats to homeostasis. In this Review, McMahon and colleagues discuss how, when such signalling becomes uncontrolled or dysfunctional, it can contribute to immune-mediated diseases and persistent pain states. Nociceptors and immune cells both protect the host from potential threats to homeostasis. There is growing evidence for bidirectional signalling between these two systems, and the underlying mechanisms are beginning to be elucidated. An understanding is emerging of how both the adaptive and innate immune systems can activate and sensitize nociceptors, and, reciprocally, how nociceptors modulate immune cells. In this Review, we discuss how these interactions can be adaptive and useful to the organism but also consider when such signalling might be maladaptive and pathophysiological, contributing to immune-mediated diseases and persistent pain states.

Few data on the pathology of cerebral vessel disease, dementia, and cognition are available. We examined the association of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer's disease dementia and cognitive function. This cross-sectional study included men and women aged 65 years or older who had yearly clinical assessments and had agreed to brain autopsy at the time of death, as part of one of two cohort studies of ageing (The Religious Orders Study and the Rush Memory and Aging Project). Individuals without dementia or with Alzheimer's disease dementia, and with complete neuropathological data, are included in our analyses. We used neuropsychological data proximate to death to create summary measures of global cognition and cognitive domains. Clinical data recorded between 1994 and 2015 were used to determine presence of Alzheimer's disease dementia. Systematic neuropathological assessments documented the severity of cerebral large vessel (atherosclerosis) and small vessel (arteriolosclerosis) disease. By use of regression analyses adjusted for demographics, gross and microscopic infarcts, and Alzheimer's disease pathology, we examined associations of vessel disease severity (mild, moderate, and severe) with odds of probable and possible Alzheimer's disease dementia and cognitive function. Study enrolment began in January, 1994, and two cohort studies are ongoing. 1143 individuals were included in our analyses (median age at death 88·8 years; 478 [42%] with Alzheimer's disease dementia). Moderate-to-severe atherosclerosis was present in 445 (39%) individuals, and arteriolosclerosis in 401 (35%) individuals. Each level increase in the severity of atherosclerosis or arteriolosclerosis was associated with significantly higher odds of Alzheimer's disease dementia (odds ratio [OR] for atherosclerosis 1·33, 95% CI 1·11–1·58; OR for arteriolosclerosis 1·20, 1·04–1·40). Atherosclerosis was associated with lower scores for global cognition (estimate −0·10 [SE 0·04], p=0·0096) and four cognitive domains (episodic memory −0·10 [0·04], p=0·017; semantic memory −0·11 [0·05], p=0·018; perceptual speed −0·14 [0·04], p=0·00080; and visuospatial abilities −0·13 [0·04], p=0·0080), but not working memory (−0·05 [0·04], p=0·21). Arteriolosclerosis was associated with lower scores for global cognition (estimate −0·10 [0·03], p=0·0015) and four domains (episodic memory −0·12 [0·04], p=0·00090; semantic memory −0·10 [0·04], p=0·013; working memory −0·07 [0·03], p=0·045; perceptual speed −0·12 [0·04], p=0·0012), and a non-significant association was noted for visuospatial abilities (−0·07 [0·03], p=0·052). Findings were unchanged in analyses controlling for the presence of APOE ε4 allele or vascular risk factors. Cerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer's disease dementia, and are also associated with low scores in most cognitive domains. Cerebral vessel pathology might be an under-recognised risk factor for Alzheimer's disease dementia. US National Institutes of Health.

يحاول ديفيد بينيت في هذا الكتاب إعادة إنتاج المفاهيم الروحية الصوفية شرقية أوغربية بطريقته المبسطة التي تخاطب القراء من غير أهل الاختصاص بما يناسب ثقافتهم وفهمهم العملاني اليومي للحياة بالطبع لا يطلق بينيت على طروحاته صفة الصوفية أو التوحد مع المعشوق (الخالق، الله) بل يقدمها من خلال مصطلحات السماوي والكوني والتماثل والنور والمحبة.

In a Perspective, David Bennett makes a case for neural reserve to be considered as a therapeutic endpoint in clinical trials for dementia.In a Perspective, David Bennett makes a case for neural reserve to be considered as a therapeutic endpoint in clinical trials for dementia.

\"In the 25 years since the 'Bodmer Report' kick-started the public understanding of science movement, there has been something of a revolution in science communication. However, despite the ever-growing demands of the public, policy-makers and the media, many scientists still find it difficult to successfully explain and publicise their activities or to understand and respond to people's hopes and concerns about their work. Bringing together experienced and successful science communicators from across the academic, commercial and media worlds, this practical guide fills this gap to provide a one-stop resource covering science communication in its many different forms. The chapters provide vital background knowledge and inspiring ideas for how to deal with different situations and interest groups. Entertaining personal accounts of projects ranging from podcasts, to science festivals, to student-run societies give working examples of how scientists can engage with their audiences and demonstrate the key ingredients in successful science communication\"-- Provided by publisher.

As the US elderly population continues to expand rapidly, Alzheimer's disease poses a major and increasing public health challenge, and older African Americans may be disproportionately burdened by the disease. Although African Americans were generally underincluded in previous research studies, new and growing evidence suggests that they may be at increased risk of the disease and that they differ from the non-Hispanic white population in risk factors and disease manifestation. This article offers an overview of the challenges of Alzheimer's disease in African Americans, including diagnosis issues, disparities in risk factors and clinical presentation of disease, and community-based recommendations to enhance research with this population. [PUBLICATION ABSTRACT]