A normal pregnancy consumes 500-800 mg of iron from the mother. Premenopausal women have a high incidence of marginal iron stores or iron deficiency (ID), with or without anemia, particularly in the ...less developed world. Although pregnancy is associated with a "physiologic" anemia largely related to maternal volume expansion; it is paradoxically associated with an increase in erythrocyte production and erythrocyte mass/kg. ID is a limiting factor for this erythrocyte mass expansion and can contribute to adverse pregnancy outcomes. This review summarizes erythrocyte and iron balance observed in pregnancy; its implications and impact on mother and child; and provides an overview of approaches to the recognition of ID in pregnancy and its management, including clinically relevant questions for further investigation.
Pure red cell aplasia Means, Robert T.
Blood,
11/2016, Letnik:
128, Številka:
21
Journal Article
Recenzirano
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Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. ...Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.
Mechanochemistry describes diverse phenomena in which mechanical load affects chemical reactivity. The fuzziness of this definition means that it includes processes as seemingly disparate as motor ...protein function, organic synthesis in a ball mill, reactions at a propagating crack, chemical actuation, and polymer fragmentation in fast solvent flows and in mastication. In chemistry, the rate of a reaction in a flask does not depend on how fast the flask moves in space. In mechanochemistry, the rate at which a material is deformed affects which and how many bonds break. In other words, in some manifestations of mechanochemistry, macroscopic motion powers otherwise endergonic reactions. In others, spontaneous chemical reactions drive mechanical motion. Neither requires thermal or electrostatic gradients. Distinct manifestations of mechanochemistry are conventionally treated as being conceptually independent, which slows the field in its transformation from being a collection of observations to a rigorous discipline. In this Review, we highlight observations suggesting that the unifying feature of mechanochemical phenomena may be the coupling between inertial motion at the microscale to macroscale and changes in chemical bonding enabled by transient build-up and relaxation of strains, from macroscopic to molecular. This dynamic coupling across multiple length scales and timescales also greatly complicates the conceptual understanding of mechanochemistry.
The biology of urate Keenan, Robert T.
Seminars in arthritis and rheumatism,
June 2020, 2020-06-00, 20200601, Letnik:
50, Številka:
3
Journal Article
Recenzirano
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Urate is the end-product of the purine metabolism in humans. The dominant source of urate is endogenous purines and the remainder comes through diet. Approximately two thirds of urate is eliminated ...via the kidney with the rest excreted in the feces. While the transporter BCRP, encoded by ABCG2, has been found to play a role in both the gut and kidney, SLC22A12 and SLC2A9 encoding URAT1 and GLUT9, respectively, are the two transporters best characterized. Only 8–12% of the filtered urate is excreted by the kidney. Renal elimination of urate depends substantially on specific transporters, including URAT1, GLUT9 and BCRP. Studies that have assessed the biologic effects of urate have produced highly variable results. Although there is a suggestion that urate may have anti-oxidant properties in some circumstances, the majority of evidence indicates that urate is pro-inflammatory. Hyperuricemia can result in the formation of monosodium urate (MSU) crystals that may be recognized as danger signals by the immune system. This immune response results in the activation of the NLRP3 inflammasome and ultimately in the production and release of interleukin-1β, and IL-18, that mediate both inflammation, pyroptotic cell death, and necroinflammation. It has also been demonstrated that soluble urate mediates effects on the kidney to induce hypertension and can induce long term epigenetic reprogramming in myeloid cells to induce “trained immunity.” Together, these sequelae of urate are thought to mediate most of the physiological effects of hyperuricemia and gout, illustrating this biologically active molecule is more than just an “end-product” of purine metabolism.
Abstract Perception, cognition, and social interaction depend upon coordinated neural activity. This coordination operates within noisy, overlapping, and distributed neural networks operating at ...multiple timescales. These networks are built upon a structural scaffolding with intrinsic neuroplasticity that changes with development, aging, disease, and personal experience. In this article, we begin from the perspective that successful interregional communication relies upon the transient synchronization between distinct low-frequency (<80 Hz) oscillations, allowing for brief windows of communication via phase-coordinated local neuronal spiking. From this, we construct a theoretical framework for dynamic network communication, arguing that these networks reflect a balance between oscillatory coupling and local population spiking activity and that these two levels of activity interact. We theorize that when oscillatory coupling is too strong, spike timing within the local neuronal population becomes too synchronous; when oscillatory coupling is too weak, spike timing is too disorganized. Each results in specific disruptions to neural communication. These alterations in communication dynamics may underlie cognitive changes associated with healthy development and aging, in addition to neurological and psychiatric disorders. A number of neurological and psychiatric disorders—including Parkinson’s disease, autism, depression, schizophrenia, and anxiety—are associated with abnormalities in oscillatory activity. Although aging, psychiatric and neurological disease, and experience differ in the biological changes to structural gray or white matter, neurotransmission, and gene expression, our framework suggests that any resultant cognitive and behavioral changes in normal or disordered states or their treatment are a product of how these physical processes affect dynamic network communication.
The prefrontal cortex (PFC), a cortical region that was once thought to be functionally insignificant, is now known to play an essential role in the organization and control of goal-directed thought ...and behavior. Neuroimaging, neurophysiological, and modeling techniques have led to tremendous advances in our understanding of PFC functions over the last few decades. It should be noted, however, that neurological, neuropathological, and neuropsychological studies have contributed some of the most essential, historical, and often prescient conclusions regarding the functions of this region. Importantly, examination of patients with brain damage allows one to draw conclusions about whether a brain area is necessary for a particular function. Here, we provide a broad overview of PFC functions based on behavioral and neural changes resulting from damage to PFC in both human patients and nonhuman primates.
Szczepanski and Knight provide a broad overview of what is currently known about the functions of different prefrontal cortex (PFC) regions based on neurological, neuropsychological, and neuropathological studies of human patients and nonhuman primates with focal brain damage to PFC.
As plastic marine debris continues to accumulate in the oceans, many important questions surround this global dilemma. In particular, how many descriptors would be necessary to model the degradation ...behavior of ocean plastics or understand if degradation is possible? Here, we report a data-driven approach to elucidate degradation trends of plastic debris by linking abiotic and biotic degradation behavior in seawater with physical properties and molecular structures. The results reveal a hierarchy of predictors to quantify surface erosion as well as combinations of features, like glass transition temperature and hydrophobicity, to classify ocean plastics into fast, medium, and slow degradation categories. Furthermore, to account for weathering and environmental factors, two equations model the influence of seawater temperature and mechanical forces.
IMPORTANCE: Chronic critical limb ischemia, marked by intractable lower extremity ischemic rest pain and tissue loss, is a highly morbid condition that leads to the loss of ambulation and decreased ...quality of life. It is associated with a high risk of limb loss and mortality and presents a significant economic burden to society. OBJECTIVE: To review the current state of epidemiology, pathophysiology, diagnosis, and treatment of critical limb ischemia. EVIDENCE REVIEW: An extensive literature search of the subject matter was conducted on material published in English between 1980 and 2016; both landmark and recently published articles were evaluated. Articles were reviewed if they included the terms critical limb ischemia, ischemic rest pain, gangrene, or extremity ulcers. FINDINGS: Critical limb ischemia represents the end stage of peripheral arterial disease. Because peripheral arterial disease is most commonly caused by atherosclerosis, critical limb ischemia is heavily associated with smoking and diabetes. Revascularization is the cornerstone of therapy to prevent limb amputation, and both open vascular surgery and endovascular therapy play a key role in the treatment of patients with critical limb ischemia. However, few scientific data are available to identify the optimal revascularization strategy, which has led to a significant amount of variability and equipoise in the treatment of this condition. Medical therapy plays a significant role in optimizing coexistent cardiovascular risk factors and a limited role in improving limb outcomes in nonrevascularizable disease. CONCLUSIONS AND RELEVANCE: Understanding critical limb ischemia and its treatment strategies is important for providing the best care for affected patients. Currently, ongoing randomized clinical trials in North America and the United Kingdom aim to provide data to support the best management of these patients.
Jupiter’s satellite Europa almost certainly hides a global saltwater ocean beneath its icy surface. Chemistry at the ice surface and ocean-rock interface might provide the building blocks for life, ...and NASA’s Europa Clipper mission will assess Europa’s habitability.
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