Annual review of medicine
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The brain is the key organ of stress processes. It determines what individuals will experience as stressful, it orchestrates how individuals will cope with stressful experiences, and it changes both functionally and structurally as a result of stressful experiences. Within the brain, a distributed, dynamic, and plastic neural circuitry coordinates, monitors, and calibrates behavioral and physiological stress response systems to meet the demands imposed by particular stressors. ⋯ Consequently, allostasis and allostatic load can jointly affect vulnerability to brain-dependent and stress-related mental and physical health conditions. This review focuses on the role of brain plasticity in adaptation to, and pathophysiology resulting from, stressful experiences. It also considers interventions to prevent and treat chronic and prevalent health conditions via allodynamic brain mechanisms.
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Annual review of medicine · Jan 2010
ReviewBiological mechanisms linking obesity and cancer risk: new perspectives.
Body mass index, as an approximation of body adiposity, is associated with increased risk of several common and less common malignancies in a sex- and site-specific manner. These findings implicate sex- and cancer site-specific biological mechanisms underpinning these associations, and it is unlikely that there is a "one system fits all" mechanism. ⋯ In this review, three novel candidate mechanisms are proposed: obesity-induced hypoxia, shared genetic susceptibility, and migrating adipose stromal cells. While public health policies aimed at curbing the underlying causes of the obesity epidemic are being implemented, there is a parallel need to better understand the biological processes linking obesity and cancer as a prerequisite to the development of new approaches to prevention and treatment.
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Although philosophers and cognitive neuroscientists have struggled to define human consciousness, physicians can identify and assess its two clinical dimensions: wakefulness and awareness. A comatose patient has neither wakefulness nor awareness; a patient in a vegetative state has wakefulness without awareness; and a minimally conscious patient has both, but awareness is impaired. ⋯ Several recent provocative studies suggest that fMRI in unresponsive patients may detect evidence of conscious awareness when a careful neurological examination cannot. If these findings are verified by future studies, functional neuroimaging technologies will alter clinical practices concerning the diagnosis, classification, and prognosis of unconscious patients, and will lead to a greater understanding of the biology of human consciousness.
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The potential role of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in endogenous repair and cell-based therapies for acute kidney injury (AKI) is under intensive investigation. Preclinical studies indicate that administered MSCs both ameliorate renal injury and accelerate repair. These versatile cells home to sites of injury, where they modulate the repair process. ⋯ This is highly controversial, however, and even those who argue there is engraftment acknowledge that the primary means of repair by these cells most likely involves paracrine and endocrine effects, including mitogenic, antiapoptotic, anti-inflammatory, and angiogenic influences. There is a good deal of interest in MSC-based approaches for the treatment of human kidney injury, thanks to positive preclinical results, the strong clinical need for novel therapies to treat AKI, the ease of isolation and expansion of MSCs, and encouraging preliminary clinical trial results in other fields. This review summarizes current knowledge and identifies gaps in our understanding of MSC biology that will need to be filled in order to translate recent discoveries into therapies for AKI in humans.
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The prevalence of invasive fungal infections (IFIs) has increased over the past three decades owing to the increasing numbers of immunocompromised hosts. These infections are associated with significant morbidity and mortality. ⋯ There have also been significant improvements in diagnostics; the galactomannan enzyme immunoassay and the beta-glucan test are now part of the EORTC/MSG criteria for diagnosis of IFI. Despite these advances, there remain a number of unanswered questions regarding optimal management of serious fungal infections, and research continues to discover and develop new therapies and evaluate new management strategies.