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Topic Review
TXNIP
Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. 
  • 481
  • 12 Apr 2021
Topic Review
Two-Pore Channels and Ca2+ Homeostasis in Immune Cells
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca2+ from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca2+ signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), were found to trigger the release of Ca2+ from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. 
  • 350
  • 16 May 2022
Topic Review
Two-Photon Imaging
Two-photon imaging (2PI) is a fluorescence-based laser scanning microscopy technique commonly used in studies across various fields of research, including neurobiology, embryology, and tissue engineering. In principle, it involves two infrared photons simultaneously exciting a single fluorophore in a sample, thereby causing it to emit light in a specific wavelength region, also called fluorescence emission spectrum. This fluorescence is normally detected in a wavelength region close to the maximum of this spectrum, allowing the sample to be identified based on its specific fluorescent characteristics.
  • 615
  • 15 Apr 2021
Topic Review
Two-Dimensional Theranostic Nanomaterials in Cancer
As the combination of therapies enhances the performance of biocompatible materials in cancer treatment, theranostic therapies are attracting increasing attention rather than individual approaches.
  • 610
  • 18 Feb 2021
Topic Review
Two-Component Regulatory Systems in Urinary Tract Infections
Two-component signaling systems (TCSs) are finely regulated mechanisms by which bacteria adapt to environmental conditions by modifying the expression of target genes. In bacterial pathogenesis, TCSs play important roles in modulating adhesion to mucosal surfaces, resistance to antibiotics, and metabolic adaptation. In the context of urinary tract infections (UTI), one of the most common types infections causing significant health problems worldwide, uropathogens use TCSs for adaptation, survival, and establishment of pathogenicity. 
  • 458
  • 10 Feb 2023
Topic Review
Two Non-Tablet Oral Formulations of L-Thyroxine
Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. 
  • 392
  • 22 Jul 2022
Topic Review
Two Complementarity Immunotherapeutics in NSCLC
The idea of using two different immunotherapies in cancer patients is based on the attempt to stimulate or inhibit different immune cells at different levels of their activity (e.g., in the lymph node and in the tumour). The most commonly used combination immunotherapy involves antibodies that target molecules capable of stimulation of the activity of lymphocytes and other immune cells and molecules that are able to inhibit this activity. Another combination immunotherapy method is the use of immune checkpoint inhibitors in combination with agents that modify the tumour microenvironment in a non-specific manner (e.g., pro-inflammatory cytokines, immunosuppressive cytokine inhibitors, and indoleamine 2,3-dioxygenase and adenosine inhibitors).
  • 335
  • 24 Jun 2021
Topic Review
Two Analytical Approaches of Quantitative Imaging
As the most lethal major cancer, pancreatic cancer is a global healthcare challenge. Personalized medicine utilizing cutting-edge multi-omics data holds potential for major breakthroughs in tackling this critical problem. Radiomics and deep learning, two trendy quantitative imaging methods that take advantage of data science and modern medical imaging, have shown increasing promise in advancing the precision management of pancreatic cancer via diagnosing of precursor diseases, early detection, accurate diagnosis, and treatment personalization and optimization. Radiomics employs manually-crafted features, while deep learning applies computer-generated automatic features. These two methods aim to mine hidden information in medical images that is missed by conventional radiology and gain insights by systematically comparing the quantitative image information across different patients in order to characterize unique imaging phenotypes. Both methods have been studied and applied in various pancreatic cancer clinical applications. 
  • 382
  • 13 Apr 2022
Topic Review
Twin-to-twin Transfusion Syndrome
The study aims to expound upon the imaging-based diagnostic methodologies aimed at identifying twin-to-twin transfusion syndrome (TTTS), a serious, somewhat rare prenatal condition which takes place in pregnancies where identical twins, or other multiples, share a placenta (monochorionic placenta), and highlighting how medico-legal outcomes can be affected by provable compliance with consolidated diagnostic best practices. In that regard, case law databases have been pored over (Justia, Lexis, Leagle), and five significant court cases have been examined and discussed, in an attempt to identify objective medico-legal standards of good practice and bring to the forefront relevant forensic dynamics. It is of utmost importance to produce a prompt diagnosis of TTTS: an early diagnosis is in fact critical in order to effectively treat and manage TTTS. By virtue of TTTS being a highly progressive condition, a delay in diagnosis can result in disastrous outcomes: just a few weeks delay in the diagnosis of TTTS can turn out fatal for both twins. Hence, most TTTS malpractice claims involve allegations of medical negligence: namely the failure to recognize the condition in a timely fashion, or to proceed with adequate diagnostic and therapeutic pathways.
  • 542
  • 25 May 2021
Topic Review
Tuskegee Syphilis Experiment
The Tuskegee Study of Untreated Syphilis in the African American Male was a clinical study conducted between 1932 and 1972 by the United States Public Health Service. The purpose of this study was to observe the natural history of untreated syphilis; the African-American men in the study were only told they were receiving free health care from the Federal government of the United States. The Public Health Service started the study in 1932 in collaboration with Tuskegee University (then the Tuskegee Institute), a historically black college in Alabama. Investigators enrolled in the study a total of 600 impoverished, African-American sharecroppers from Macon County, Alabama. Of these men, 399 had latent syphilis, with a control group of 201 men who were not infected. As an incentive for participation in the study, the men were promised free medical care, but were deceived by the PHS, who disguised placebos, ineffective methods, and diagnostic procedures as treatment. The men who had syphilis were never informed of their diagnosis, despite the risk of infecting others, and the fact that the disease could lead to blindness, deafness, mental illness, heart disease, bone deterioration, collapse of the central nervous system, and death.. According to the Centers for Disease Control and Prevention, the men were told that they were being treated for "bad blood,” a colloquialism that described various conditions such as syphilis, anemia and fatigue. "Bad blood"—specifically the collection of illnesses the term included—was a leading cause of death within the southern African-American community. The men were initially told that the study was only going to last six months, but it was extended to 40 years. After funding for treatment was lost, the study was continued without informing the men that they would never be treated. None of the infected men were treated with penicillin despite the fact that by 1947, the antibiotic had become the standard treatment for syphilis. Study clinicians could have chosen to treat all syphilitic subjects and close the study, or split off a control group for testing with penicillin. Instead, they continued the study without treating any participants; they withheld treatment and information about it from the subjects. In addition, scientists prevented participants from accessing syphilis treatment programs available to other residents in the area. The study continued, under numerous Public Health Service supervisors, until 1972, when a leak to the press resulted in its termination on November 16 of that year. The victims of the study, all African-American, included numerous men who died of syphilis, 40 wives who contracted the disease and 19 children born with congenital syphilis. The 40-year Tuskegee Study of Untreated Syphilis in the African American Male study was a major violation of ethical standards. Researchers knowingly failed to treat participants appropriately after penicillin was proven to be an effective treatment for syphilis and became widely available. Moreover, participants remained ignorant of the study clinicians’ true purpose, which was to observe the natural course of untreated syphilis. The revelation in 1972 of study failures by a whistleblower, Peter Buxtun, led to major changes in U.S. law and regulation concerning the protection of participants in clinical studies. Now studies require informed consent, communication of diagnosis and accurate reporting of test results. The Tuskegee Syphilis Study, cited as "arguably the most infamous biomedical research study in U.S. history," led to the 1979 Belmont Report and to the establishment of the Office for Human Research Protections (OHRP). It also led to federal laws and regulations requiring institutional review boards for the protection of human subjects in studies involving them. The OHRP manages this responsibility within the United States Department of Health and Human Services (HHS). On May 16, 1997, President Bill Clinton formally apologized on behalf of the United States to victims of the study.
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  • 07 Nov 2022
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