Adv Exp Med Biol
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Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence. Disruption of gene expression patterns which are governed by epigenetics can result in autoimmune diseases, cancers, and various other maladies. Mechanisms of epigenetics include DNA methylation (and demethylation), histone modifications, and non-coding RNAs such as microRNAs. ⋯ In contrast to genetic changes, which are difficult to reverse, epigenetic aberrations can be pharmaceutically reversible. The emerging tools of epigenetics can be used as preventive, diagnostic, and therapeutic markers. With the development of drugs that target the specific epigenetic mechanisms involved in the regulation of gene expression, development and utilization of epigenetic tools are an appropriate and effective approach that can be clinically applied to the treatment of various diseases.
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Immunoglobulins are key effector molecules in the humoral immune response. Intravenous polyspecific immunoglobulin (IVIG) is a preparation of polyclonal serum immunoglobulins, typically IgG, from thousands of donors. It has been used as adjunctive therapy in critically ill patients with severe infections, i.e. sepsis, septic shock, and necrotizing soft tissue infections. ⋯ A blinded, placebo-controlled clinical trial (INSTINCT) assessed the effect of IVIG in 100 intensive care unit patients with necrotizing soft tissue infections, including all bacterial etiologies. The study did not demonstrate any effect on self-reported physical functioning at 6 months. In this chapter, we review the mechanisms of action of IVIG and the clinical studies that are available for necrotizing soft tissue infections as well as severe group A streptococcal infections.
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Case Reports Multicenter Study
Necrotizing Soft Tissue Infections: Case Reports, from the Clinician's Perspectives.
Necrotizing soft tissue infections (NSTI) are rapidly spreading and life-threatening infections of skin and soft tissue. Essentially there are two types of NSTI, based on the invasive microorganisms. The speed of development and associated clinical features differ markedly depending on the bacterial etiology. ⋯ In this chapter, we present three cases from the INFECT-study population. This study was an international, multicenter, prospective cohort study of adult patients with NSTI. We describe the clinical presentations, pre-, peri-, and postoperative clinical findings, microbiology, and treatment in cases of monobacillary Streptococcus pyogenes necrotizing soft tissue infections NSTI, polymicrobial infection, and an unusual presentation of pelvic monobacillary S. pyogenes infection in an immunocompromised patient.
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Myeloid-derived suppressor cells (MDSCs) represent a heterogenous population of immature myeloid cells capable of modulating immune responses. In the context of cancer, MDSCs are abnormally produced and recruited to the tumor microenvironment (TME) to aid in the establishment of an immunosuppressive TME that facilitates tumor escape. ⋯ In this chapter, we review MDSC characterization, development, expansion, and mechanisms that facilitate immunosuppression and tumor progression. Furthermore, we highlight studies demonstrating the clinical significance of MDSCs in various disease states in addition to strategies that modulate various aspects of MDSC biology for therapeutic gain.
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The breast tissue undergoes significant physiological change during pregnancy and lactation. These changes can give rise to some unique disorders during pregnancy , puerperium and lactation or exaggerate pre-existing conditions. Clinical examination becomes less reliable due to textural change and density of breast tissue as a result of hormonal changes. ⋯ While ultrasound is the investigation of choice, mammography can be performed with abdominal shielding if malignancy is suspected. Core biopsy is necessary for evaluation of any breast pathology but it comes with risk of infection, bleeding, hematoma and even milk fistula. The treating clinical specialist must be aware of certain unusual unique clinical conditions in pregnancy and lactation including accessory axillary breast tissue, gigantomastia and Raynaud's phenomenon.