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Topic Review
Qualitative Evidence for Return-to-Work
Chronic musculoskeletal pain (CMSP) (i.e., pain duration >3 months) such as chronic neck/shoulder and back pain or generalized widespread pain (including fibromyalgia (FM)) has a prevalence from 10.4% to 20% among adults.
  • 702
  • 19 Apr 2021
Topic Review
Therapeutic Strategies for Diabetic Kidney Disease (DKD)
The key approach to reduce diabetic kidney disease (DKD)-mediated end-stage renal disease (ESRD)  is to prevent and delay the renal function decline, as once a fall in renal function occurs, it is difficult to regain, apart from when normoglycemic conditions are implemented for a long time, such as following pancreas transplantation. In parallel to lifestyle, glycemic and blood pressure control, all cornerstones for the prevention of DKD, the researchers outline five major treatment “pillars” that possess major renal protective properties
  • 701
  • 18 May 2023
Topic Review
Statin Intolerance
Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. 
  • 700
  • 17 Apr 2023
Topic Review
Resveratrol Effects on Atherosclerosis Progression
The beneficial effects of a Mediterranean diet are due to the numerous active compounds in the food and, particularly, the high concentration of compounds with synergistically acting antioxidant properties. Resveratrol, a stilbenoid nonflavonoid phenol, is an antioxidant that is naturally produced by numerous plants as a defensive agent in response to attacks from pathogens, such as bacteria and fungi. Resveratrol has several effects on human health, including on the lipid profile, where it primarily downregulates the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, reducing the synthesis of cholesterol. Resveratrol also increases the expression of low-density lipoprotein (LDL) receptors in the liver, contributing to the reduction in the LDL-cholesterol levels. 
  • 700
  • 31 May 2023
Topic Review
The Challenge of Assessing Benefit-Risk of Older Drugs
Evidence-based pain therapy should rely on precisely defined and personalized criteria. This includes balancing the benefits and risks not only of single drugs but often requires complex between-drug comparisons. Non-steroidal anti-inflammatory drugs (NSAIDs) have been available for several decades and their use is described in an abundance of guidelines. Most of these guidelines recommend that ‘the selection of a particular NSAID should be based on the benefit-risk balance for each patient’. However, head-to-head studies are often lacking or of poor quality, reflecting the lower standards for clinical research and regulatory approval at the time. The inconsistency of approved indications between countries due to national applications adds to the complexity. Finally, a fading research interest once drugs become generic points to a general deficit in the post-marketing evaluation of medicines. Far from claiming completeness, this research illustrates the challenges that physicians encounter when trying to balance benefits and risks in a situation of incomplete and inconsistent data on longstanding treatment concepts. Ibuprofen and mefenamic acid, the most frequently sold NSAIDs in Austria, serve as examples. The illustrated principles are, however, not specific to these drugs and are generalizable to any comparison of older drugs in daily clinical practice. 
  • 698
  • 08 Nov 2022
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. 
  • 697
  • 17 Mar 2022
Topic Review
Non-Coding RNAs in Tamoxifen Resistance
Despite the clinical efficacy of Tam, intrinsic or acquired resistance is an important obstacle limiting the success of ER + breast cancer patient treatment. It is a challenge that needs to be overcome to improve the prognosis of these patients. The main mechanisms of resistance to tamoxifen can be divided according to different causes: mechanisms that involve genetic mutations and lead to loss or gain of function of the receptor and mechanisms that modulate other protumorigenic pathways, including other receptors involved in estrogen’s pathway of action.
  • 694
  • 09 Aug 2021
Topic Review
Targeted Therapies for Familial Hypercholesterolemia
Several new targeted therapies were developed for familial hypercholesterolemia, and some are being tested to achieve the low-density lipoprotein (LDL)-C goals for high-/very-high-risk familial hypercholesterolemia (FH) patients as recommended by the ESC/EAS 2016–2019 guidelines. The advantage of targeted therapies is that they provide clinicians with the power to practice personalized or precision medicine with the aim of achieving better risk/benefit and cost/effectiveness of therapies.
  • 694
  • 15 Nov 2022
Topic Review
Neuroglia in Administrating Nerve Blockers and Anesthesia
Dysfunction of the neuroglia can have profound consequences on the blood–brain barrier (BBB). Studies have shown that the disruption of astrocytic–endothelial interaction can compromise the permeability of BBB and its effectiveness in selectively regulating the exchange of substances. Microglia have been recognized to have a significant role in the initiation of chronic pain and in its interactions with various nerve blockers and anesthetic agents. Microglia have a role in pain resolution via a pathway that involves Cannabinoid receptor type 2 activation and MAP kinase phosphorylation. 
  • 694
  • 26 Feb 2024
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. 
  • 690
  • 18 Oct 2022
Topic Review
The Products of Bone Resorption
Surprisingly little is known about the factors released from bone during resorption and the metabolic roles they play. This entry describes what we have learned about factors released from bone, mainly through the study of burn injuries, and what roles they play in post-burn metabolism. From these studies, we know that calcium, phosphorus, and magnesium, along with transforming growth factor (TGF)-β, are released from bone following resorption. Additionally, studies in mice from Karsenty’s laboratory have indicated that undercarboxylated osteocalcin is also released from bone during resorption. Questions arising from these observations are discussed as well as a variety of potential conditions in which release of these factors could play a significant role in the pathophysiology of the conditions. Therapeutic implications of understanding the metabolic roles of these and as yet other unidentified factors are also raised. While much remains unknown, that which has been observed provides a glimpse of the potential importance of this area of study.
  • 689
  • 12 Apr 2021
Topic Review
mPR-Mediated Signaling with Other Steroid Signaling Pathways
Progesterone (PRG) is a key cyclical reproductive hormone that has a significant impact on female organs in vertebrates. It is mainly produced by the corpus luteum of the ovaries, but can also be generated from other sources such as the adrenal cortex, Leydig cells of the testes and neuronal and glial cells. PRG has wide-ranging physiological effects, including impacts on metabolic systems, central nervous systems and reproductive systems in both genders. It was first purified as an ovarian steroid with hormonal function for pregnancy, and is known to play a role in pro-gestational proliferation during pregnancy.
  • 687
  • 05 Jun 2023
Topic Review
Treatment of Preterm Infants at Border of Viability
Decision-making at the border of viability remains challenging for the expectant parents and the medical team. The preterm infant is dependent on others making the decision that will impact them for a lifetime in hopefully their best interest. Besides survival and survival without neurodevelopmental impairment, other relevant outcome measures, such as the quality of life of former preterm infants and the impact on family life, need to be integrated into prenatal counselling.
  • 679
  • 17 Mar 2022
Topic Review
SL-401 (Tagraxofusp)
Overcoming the leukemia stem cell resistance to intensive chemotherapy has been an area of extensive research over the last two decades. Advances and greater understanding of the molecular biology of leukemia stem cells are in rapid progress. Targeted therapies are currently being used in clinical practice with reasonable response rates, but a cure is being achieved in only a small percentage of patients, most likely due to tumor mutational heterogeneity. A genetically engineered diphtheria toxin fused with interleukin-3 (SL-401 or tagraxofusp) has shown robust activity in blastic plasmacytoid dendritic cell neoplasm and promising response rates in different myeloid malignancies, including eradication of minimal residual disease. Multiple clinical trials are being conducted using this drug and the preliminary results are encouraging. 
  • 675
  • 07 Jul 2021
Topic Review
Cholesterol Remnants
Randomized clinical trials with statins and other lipid-lowering drugs have shown the presence of a “residual cardiovascular risk” in those treated to “target” for LDL-cholesterol. This risk is mainly associated to lipid components other than LDL and in particular to remnant cholesterol (RC) and to lipoproteins rich in triglycerides in fasting and non-fasting conditions. Remnant lipoproteins and inflammation, as well as LP (a), are causally related to risk of ACVD in individuals already treated with statin therapyremnant lipoproteins and inflammation, as well as LP (a), are causally related to risk of ACVD in individuals already treated with statin therapyremnant lipoproteins and inflammation, as well as LP (a), are causally related to risk of ACVD in individuals already treated with statin therapy.
  • 675
  • 10 Mar 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.
  • 672
  • 01 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. 
  • 672
  • 19 Oct 2023
Topic Review
Skeletal Effects of Tanshinones
Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of Salvia miltiorrhiza with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. 
  • 671
  • 25 Apr 2021
Topic Review
Diagnostic Approaches for Epstein–Barr Virus
Epstein–Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV.
  • 670
  • 23 Mar 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.
  • 669
  • 18 May 2021
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