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New perspectives on difficult-to-treat tuberculosis based on old therapeutic approaches.
Mondoni, M, Centanni, S, Sotgiu, G
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2020;:S91-S99
Abstract
Tuberculosis (TB) is an important clinical and public health issue worldwide. Despite improved treatment success rates following the introduction of antibiotics in daily clinical practice, the expected decline in incidence has been hampered by HIV epidemics and multi- and extensively drug-resistant TB. During the pre-antibiotic era, TB therapies were mainly based on improving hygiene conditions, strengthening the immune system, and targeting the rest of the affected lungs with invasive techniques. Detailed knowledge of old non-pharmacological therapies might support physicians and researchers in the identification of new solutions for difficult-to-treat patients. We performed a narrative literature review on the main old therapeutic options prescribed for patients with TB. The main recommendations and contraindications of sanatorium therapies (i.e., bed rest, fresh air, sunlight) and pulmonary collapse techniques are reviewed, evaluating their physiological basis and their impact on patient outcomes. We report studies describing new interventional pulmonary and surgical techniques and assess new perspectives based on old medical and surgical treatments, whose potential implementation could help complicated patients.
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Psoriasis and Treatment: Past, Present and Future Aspects.
Reid, C, Griffiths, CEM
Acta dermato-venereologica. 2020;(3):adv00032
Abstract
The management of psoriasis has evolved considerably over the past 100 years. This has occurred in parallel with our understanding of the pathogenesis of this common, complex and enigmatic disease. It should be celebrated as an outstanding example of successful translational research. With precise targeting of immune pathways for the treatment of psoriasis with new biologics and small molecules has come the realisation that the most effective approach to patient management is a holistic one which encompasses the biopsychosocial nature of the disease. This involves a stratified medicine approach to identifying the best drug for an individual allied to patient education, screening for comorbidity, and regular review as both the clinical presentation and the patient's needs will change over time. Al-though there is not yet a cure for psoriasis - the whole person, systems approach to patient management, that is in part dependent on early intervention, should help to ensure an optimal outcome.
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Decreased Mortality of falciparum Malaria in Anemic Prisoners of War?
Shanks, GD
The American journal of tropical medicine and hygiene. 2020;(6):2171-2173
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Abstract
Modern clinical trials have suggested that anemia protects against malaria mortality. Military records of the Second World War in Asia were examined to see if there was support for this hypothesis. When relatively well-nourished Imperial Japanese Navy sailors captured on Nauru (n = 799) were imprisoned on the Fauro Islands, 26% died from falciparum malaria. Similarly treated but very malnourished colocated Imperial Army soldiers experienced low stable malaria mortality. One-fifth of previously healthy Australian Army soldiers (n = 252) retreating from New Britain died largely because of malaria in April 1942. Malnourished prisoners of war, who were as a group very anemic, both Australian Army soldiers in Thailand and Japanese Army soldiers in Papua New Guinea, had high malaria rates but very low (< 3%) mortality rates. Malaria immunity does not adequately explain this dichotomy, suggesting that severe nutritional deprivation may be protective against malaria mortality possibly because of iron-deficiency anemia.
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[Nutriome as the direction of the "main blow": determination of physiological needs in macro- and micronutrients, minor biologically active substances].
Tutelyan, VA, Nikityuk, DB, Baturin, AK, Vasiliev, AV, Gapparov, MG, Zhilinskaya, NV, Zhminchenko, VM, Kambarov, AO, Kodentsova, VM, Kravchenko, LV, et al
Voprosy pitaniia. 2020;(4):24-34
Abstract
One of the essential parts of fundamental research in Nutrition Science is the determination of the physiological requirements of humans for energy and food substances. Research that has been carried out in this area over the past 90 years, consistently develops and improves the norms of physiological requirements for energy and nutrients for various groups of the population of the Russian Federation. In the 50 years of the last century in this research field, determining the values of daily intake for macronutrients (proteins, lipids and carbohydrates), was in the first place. Then the Era of micronutrients (vitamins, minerals, trace elements) was started, and, finally, now there is the Era of minor food biologically active substances. More and more facts are accumulating about their leading role in regulating metabolism. They can be recognized as endogenous regulators, the primary vital components involved in the formation of human health. In recent years, the new definition of Nutriome is introduced into Nutrition Science. It is considered as a set of essential nutritional factors to maintain a dynamic equilibrium between human being and the environment, aimed to ensure viability, the preservation and reproduction of the species, keeping the adaptive capacity, the system of antioxidant defence, apoptosis, metabolism, and immune system function. The Nutriome is a formula for optimal nutrition, which is continually being improved and supplemented. Knowledge of this formula is the key to forming an optimal diet for a person, and, therefore, to save their health. It is evident that at the population level, the Nutriome has its characteristics, its structure for each age period of human life. The need to develop a formula for optimal nutrition and, consequently, updating nutrient-based dietary guidelines is induced by socio-economic and demographic changes in population, changes in anthropometric characteristics of children and adults, increasing prevalence of socially significant non-communicable diseases, developing studies of the significance of particular food substances and establishing the relationship between nutrition and health.
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Can phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (COVID-19)?
Levy, E, Delvin, E, Marcil, V, Spahis, S
American journal of physiology. Endocrinology and metabolism. 2020;(4):E689-E708
Abstract
Much more serious than the previous severe acute respiratory syndrome (SARS) coronavirus (CoV) outbreaks, the novel SARS-CoV-2 infection has spread speedily, affecting 213 countries and causing ∼17,300,000 cases and ∼672,000 (∼+1,500/day) deaths globally (as of July 31, 2020). The potentially fatal coronavirus disease (COVID-19), caused by air droplets and airborne as the main transmission modes, clearly induces a spectrum of respiratory clinical manifestations, but it also affects the immune, gastrointestinal, hematological, nervous, and renal systems. The dramatic scale of disorders and complications arises from the inadequacy of current treatments and absence of a vaccine and specific anti-COVID-19 drugs to suppress viral replication, inflammation, and additional pathogenic conditions. This highlights the importance of understanding the SARS-CoV-2 mechanisms of actions and the urgent need of prospecting for new or alternative treatment options. The main objective of the present review is to discuss the challenging issue relative to the clinical utility of plants-derived polyphenols in fighting viral infections. Not only is the strong capacity of polyphenols highlighted in magnifying health benefits, but the underlying mechanisms are also stressed. Finally, emphasis is placed on the potential ability of polyphenols to combat SARS-CoV-2 infection via the regulation of its molecular targets of human cellular binding and replication, as well as through the resulting host inflammation, oxidative stress, and signaling pathways.
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From traditional remedies to cutting-edge medicine: Using ancient mesoamerican knowledge to address complex disorders relevant to psychoneuroimmunology.
Pedraza-Alva, G, Ramírez-Serrano, CE, Pedraza, F, Flores-Vallejo, RDC, Villarreal, ML, Pérez-Martínez, L
Brain, behavior, and immunity. 2019;:3-5
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Aspergillus fumigatus and Aspergillosis in 2019.
Latgé, JP, Chamilos, G
Clinical microbiology reviews. 2019;(1)
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Abstract
Aspergillus fumigatus is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of A. fumigatus; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against Aspergillus in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of A. fumigatus.
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Landscape of systemic therapy for ovarian cancer in 2019: Primary therapy.
Fujiwara, K, Hasegawa, K, Nagao, S
Cancer. 2019;:4582-4586
Abstract
According to the statement from the 5th Ovarian Cancer Consensus Conference in 2015, the primary systemic chemotherapy for advanced ovarian cancer is a combination of paclitaxel plus carboplatin administered every 3 weeks (PCq3w). Optional alternatives include weekly dose-dense paclitaxel, in combination and maintenance therapy with bevacizumab, and intraperitoneal chemotherapy. Since then, in addition to the PCq3w strategy, there has been emerging new evidence, especially for poly(adenosine diphosphate-ribose) polymerase inhibitors. Moreover, there are multiple randomized, phase 3 trials testing the addition of antiangiogenic and/or immune checkpoint inhibitors in this patient population. In this article, current and future perspectives of systemic chemotherapy for advanced ovarian cancer are discussed.
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Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age.
Barrila, J, Crabbé, A, Yang, J, Franco, K, Nydam, SD, Forsyth, RJ, Davis, RR, Gangaraju, S, Ott, CM, Coyne, CB, et al
Infection and immunity. 2018;(11)
Abstract
Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.
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Mitochondrial Toxicity.
Meyer, JN, Hartman, JH, Mello, DF
Toxicological sciences : an official journal of the Society of Toxicology. 2018;(1):15-23
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Abstract
Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity. We also discuss the potential importance of hormetic effects of mitochondrial stressors. Finally, we comment on future areas of research we consider critical for mitochondrial toxicology, including increased integration of clinical, experimental laboratory, and epidemiological (human and wildlife) studies; improved understanding of biomarkers in the human population; and incorporation of other factors that affect mitochondria, such as diet, exercise, age, and nonchemical stressors.