Topic Review
Novel Oral Anticoagulants
The use of novel oral anticoagulants in patients with impaired renal function or undergoing immunosuppressive therapy is limited due to the risk of drug-to-drug interactions and anticoagulation-related adverse events. Novel oral anticoagulants (NOACs) have been commonly used in patients facing a higher risk of cardiovascular (CV) incidents such as atrial fibrillation (AF) and venous thrombo-embolic events (VTE), successfully decreasing numbers of CV incidents in the general population. The probability of those incidents increases in specific groups of patients, including those with chronic kidney disease (CKD) where the risk of developing AF averages between 19–24%, reaching up to 27% in patients with end-stage kidney disease (ESKD).
  • 422
  • 04 Jul 2022
Topic Review
Control Mastery Theory
Control mastery theory or CMT is an integrative theory of how psychotherapy works, that draws on psychodynamic, relational and cognitive principles. Originally the theory was developed within a psychoanalytical framework, by psychoanalyst and researcher Joseph Weiss, MD (1924-2004). CMT is also a theory of how the mind operates, with an emphasis of the unconscious, and how psychological problems may develop based on traumatic experiences early in life. The name of the theory comes from two central premises; the assumption that people have control over their mental content, and the belief that patients who come to therapy are fundamentally motivated to master their lives.
  • 422
  • 25 Oct 2022
Topic Review
Endothelial Dysfunction and Chronic Inflammation
Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues.
  • 421
  • 31 Jan 2023
Topic Review
Ivacaftor Treatment in Cystic Fibrosis
Cystic fibrosis (CF) is a rare, progressive, multi-organ genetic disease. CF results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which lead to defective transport of chloride and sodium ions across the epithelial cell membrane of multiple organs, including the lungs, pancreas, gallbladder, intestine, and reproductive system. The recently developed CFTR modulators treat the underlying cause of CF. Ivacaftor (Kalydeco®, Vertex Pharmaceuticals Incorporated, Boston, MA, USA), a small-molecule CFTR modulator, was the first approved CFTR modulator. Although clinical trials have provided valuable evidence on the safety and efficacy of ivacaftor, it is important that real-world outcomes in routine clinical practice are understood. Here, we systematically reviewed data from real-world observational studies of ivacaftor treatment in people with CF.
  • 420
  • 09 Jun 2021
Topic Review
Biomarkers of Inflammation for Management of Diabetes
Virus infection, inflammation and genetic factors are important factors in the pathogenesis of diabetes mellitus. The nuclear factor-kappa B (NF-κB) is a family of transcription factors that bind the enhancer of the κ light chain gene of B cell immunoglobulin. NF-κB plays an essential role in the activation and development of B cells, and the activation of NF-κB is critical in the inflammation and development of diabetes mellitus. Recently, immunoglobulin-free light chain (FLC) λ was found to be increased in the sera of patients with diabetes mellitus, and the FLC λ and κ/λ ratios are more specific and sensitive markers for the diagnosis of diabetes relative to glycated hemoglobin A1c. Thus, FLCs may be promising biomarkers of inflammation that could relate to the activation of NF-κB. 
  • 413
  • 17 Mar 2022
Topic Review
Vitamin D and Microbiota
Microbiome studies have already demonstrated unique microbial patterns in systemic autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. Dysbiosis also seems to be associated with allergies, in particular asthma, atopic dermatitis, and food allergy.
  • 413
  • 28 Oct 2022
Topic Review
Different Parameters for the Diagnosis of Diabetes
Both immediate and lingering health issues are associated with diabetes mellitus. Therefore, it is crucial to find it at a very early stage. Recently, using implanted bioelectronics to assess physiological markers has been used as a therapeutic or diagnostic tool in medicine. Conditions include diabetes, diabetic foot, heart disease, kidney failure, and stroke can all cause death. Patients with early-stage diabetes may not exhibit any clinical symptoms, making it challenging to recognize them. Continuous blood glucose and urine monitoring are necessary in daily life for diabetes prevention and early treatment.
  • 413
  • 11 Apr 2023
Topic Review
Intravenous Moderate and Deep Sedation
Successful pharmacological innovations that have made a difference in daily practice are rare in the world of anesthesia and sedation. After many years of research, it seems that we finally have two new drug innovations that are likely to change the paradigm of moderate and deep sedation. These are oliceridine and remimazolam. Both have been in development for over a decade. Oliceridine was synthesized in a lab as an entirely new molecule. It is a biased μ- receptor agonist that acts preferentially on the G-protein pathway (which is responsible for analgesia). At least in lower doses, it has minimal effect on the beta-arrestin pathway, which is responsible for unwanted effects of μ-opioid receptor activation such as respiratory depression and gastrointestinal dysfunction. Like any other μ- receptor agonist, it produces appropriate dose-dependent analgesia. Remimazolam is structurally similar to midazolam; however, it has an additional ester linkage that delivers the kinetics of remifentanil. As a result, while pharmacodynamically identical to midazolam, remimazolam is metabolized by ester hydrolysis and subsequently its elimination is rapid and predictable.
  • 412
  • 01 Jul 2021
Topic Review
Emotional Flooding
Emotional flooding is a form of psychotherapy that involves attacking the unconscious and/or subconscious mind to release repressed feelings and fears. Many of the techniques used in modern emotional flooding practice have roots in history, some tracing as far back as early tribal societies. For more information on emotional flooding, see Flooding (psychology).
  • 410
  • 01 Nov 2022
Topic Review
Acyldepsipeptide Analogues for Tuberculosis Treatment
Acyldepsipeptides (ADEPs) are a new class of emerging antimicrobial peptides (AMPs), which are currently explored for treatment of pathogenic infections, including tuberculosis (TB). These cyclic hydrophobic peptides have a unique bacterial target to the conventional anti-TB drugs, and present a therapeutic window to overcome Mycobacterium Tuberculosis (M. tb) drug resistance. ADEPs exerts their antibacterial activity on M. tb strains through activation of the protein homeostatic regulatory protease, the caseinolytic protease (ClpP1P2). ClpP1P2 is normally regulated and activated by the ClpP-ATPases to degrade misfolded and toxic peptides and/or short proteins. ADEPs bind and dysregulate all the homeostatic capabilities of ClpP1P2 while inducing non-selective proteolysis. The uncontrolled proteolysis leads to M. tb cell death within the host. ADEPs analogues that have been tested possess cytotoxicity and poor pharmacokinetic and pharmacodynamic properties
  • 403
  • 30 Sep 2022
Topic Review
Effects of Photo-Crosslinking Hydrogels in Wound Healing
Wound healing is a dynamic physiological process, including three stages: inflammation, tissue formation, and remodeling. The quality of wound healing is affected by many topical and systemic factors, while any small factor may affect the process. Therefore, improving the quality of wound healing is a complex and arduous challenge. Photo-crosslinking reaction using visible light irradiation is a novel method for hydrogel preparation. Photo-crosslinking hydrogels can be controlled in time and space, and are not interfered by temperature conditions, which have been widely used in the fields of medicine and engineering. 
  • 401
  • 18 Oct 2022
Topic Review
UVA-Degradable Collagenase Nanocapsules
Peyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy. Herein, we present a novel methodology for the preparation of collagenase nanocapsules without affecting its enzymatic activity and capable of releasing the enzyme in response to an ultraviolet A (UVA) light stimulus.
  • 400
  • 18 May 2021
Topic Review
N-Acetyl-Beta-D-Glucosaminidase in Kidney Injury
Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs).
  • 398
  • 18 Apr 2023
Topic Review
Effects of Tirzepatide in Spectrum of Metabolic Diseases
The prevalence of metabolic diseases including type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD) increases globally. This highlights an unmet need for identifying optimal therapies for the management of these conditions. Tirzepatide is a novel dual incretin receptor agonist (twincretin) that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.
  • 396
  • 05 Jul 2023
Topic Review
TDM of Antiseizure Medications
Therapeutic drug monitoring (TDM) of antiseizure medications (ASMs) represents a valuable tool to establish an appropriate patient therapy, to collect important information about drugs’ interactions and to evaluate patient’s metabolic capabilities. In recent years, a new volumetric absorptive microsampling technique using VAMS® technology and Mitra® devices, consisting of a sampling technique for the collection of fixed-volume capillary blood, was developed. These new devices provide a new home-sampling technique for whole blood that has been spread out to simplify sample collection from finger-pricks. 
  • 393
  • 08 Jul 2021
Topic Review
The Ca2+ Sensor STIM in Human Diseases
The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca2+ entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca2+ sensors in the endoplasmic reticulum (ER) and, upon Ca2+ store discharge, interact with and activate the Orai/CRACs in the plasma membrane. Dysregulation of Ca2+ signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders. 
  • 393
  • 19 Oct 2023
Topic Review
Physiological Roles of TRPM4
Transient receptor potential melastatin 4 (TRPM4) is a unique member of the TRPM protein family and, similarly to TRPM5, is Ca2+ sensitive and permeable for monovalent but not divalent cations. It is widely expressed in many organs and is involved in several functions; it regulates membrane potential and Ca2+ homeostasis in both excitable and non-excitable cells. 
  • 387
  • 11 Jan 2022
Topic Review
Therapies for Chronic Kidney Disease-Related Protein Energy Wasting
Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, “sterile” muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering “sterile” tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle.
  • 386
  • 12 Jul 2023
Topic Review
Immunohistochemical Profile of Parathyroid Tumours
Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022).
  • 384
  • 28 Jul 2022
Topic Review
Neuro-Inflammaging and Psychopatological Distress
Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. Aging and inflammation have been defined in their interplay since the 1991 New York Academy of Sciences conference by a group of researchers. It ihas been suggested that  biological, chemical, and physics damage led to a chronic inflammatory process. The link between the molecular and cellular balance capable of permitting a physiological healthy aging or a cognitive impairment is still unclear. The innate immune system plays a crucial role in the inflammatory processes, usually reduced at advanced ages. In the elderly, senescent microglia augment the production of proinflammatory mediators with reduced chemotaxis and phagocytosis capacities, particularly of amyloid-β fibrils. The raised systemic inflammatory state and peripheral immunosenescence interfere with neuronal immune cell activity and reactivity.
  • 384
  • 28 Jun 2023
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