Challenges and Solutions in Automated Tongue Diagnosis Techniques: A Review.

Tongue diagnosis is used in various traditional medicine cultures as a non-invasive method for assessing an individual's health. Tongue image analysis has the potential for assessing the metabolism and functionality of the internal organs, making it a quick method of diagnosis. As automated systems give quantitative and objective results thereby effective in facilitating diagnosis, a review was conducted to evaluate literature on current methods of tongue diagnosis.

Blockade of Organic Anion Transport in Humans After Treatment With the Drug Probenecid Leads to Major Metabolic Alterations in Plasma and Urine.

Probenecid is used to treat gout and hyperuricemia as well as increase plasma levels of antiviral drugs and antibiotics. In vivo, probenecid mainly inhibits the renal SLC22 organic anion transporters OAT1 (SLC22A6), OAT3 (SLC22A8), and URAT1 (SLC22A12). To understand the endogenous role of these transporters in humans, we administered probenecid to 20 healthy participants and metabolically profiled the plasma and urine before and after dosage.

Molecular Properties of Drugs Handled by Kidney OATs and Liver OATPs Revealed by Chemoinformatics and Machine Learning: Implications for Kidney and Liver Disease.

In patients with liver or kidney disease, it is especially important to consider the routes of metabolism and elimination of small-molecule pharmaceuticals. Once in the blood, numerous drugs are taken up by the liver for metabolism and/or biliary elimination, or by the kidney for renal elimination. Many common drugs are organic anions.

Coordinate regulation of systemic and kidney tryptophan metabolism by the drug transporters OAT1 and OAT3.

How organs sense circulating metabolites is a key question. Here, we show that the multispecific organic anion transporters of drugs, OAT1 (SLC22A6 or NKT) and OAT3 (SLC22A8), play a role in organ sensing. Metabolomics analyses of the serum of Oat1 and Oat3 knockout mice revealed changes in tryptophan derivatives involved in metabolism and signaling.

Association of Race and Major Adverse Cardiac Events (MACE): The Atherosclerosis Risk in Communities (ARIC) Cohort.

Background And Aims: To evaluate the association of self-reported race with major adverse cardiac events (MACE) and modification of this association by paraoxonase gene (1, 2, and 3) single nucleotide polymorphisms (SNPs).

Methods: Included in this longitudinal study were 12,770 black or white participants from the Atherosclerosis Risk in Communities (ARIC) cohort who completed a baseline visit (1987-1989) with genotyping. Demographic, behavioral, and health information was obtained at baseline.

Outpatient Pharmacy Prescriptions During the First Year Following Serious Combat Injury: A Retrospective Analysis.

Introduction: Limited research has analyzed the full range of outpatient medication prescription activity following serious combat injury. The objectives of this study were to describe (1) outpatient medication prescriptions and refills during the first 12 months after serious combat injury, (2) longitudinal changes in medication prescriptions during the first-year postinjury, and (3) patient characteristics associated with outpatient prescriptions.

Materials And Methods: This was a retrospective analysis of existing health and pharmacy data for a random sample of U.

The Systems Biology of Drug Metabolizing Enzymes and Transporters: Relevance to Quantitative Systems Pharmacology.

Quantitative systems pharmacology (QSP) has emerged as a transformative science in drug discovery and development. It is now time to fully rethink the biological functions of drug metabolizing enzymes (DMEs) and transporters within the framework of QSP models. The large set of DME and transporter genes are generally considered from the perspective of the absorption, distribution, metabolism, and excretion (ADME) of drugs.

Unique metabolite preferences of the drug transporters OAT1 and OAT3 analyzed by machine learning.

The multispecific organic anion transporters, OAT1 (SLC22A6) and OAT3 (SLC22A8), the main kidney elimination pathways for many common drugs, are often considered to have largely-redundant roles. However, whereas examination of metabolomics data from -knockout mice ( and ) revealed considerable overlap, over a hundred metabolites were increased in the plasma of one or the other of these knockout mice. Many of these relatively unique metabolites are components of distinct biochemical and signaling pathways, including those involving amino acids, lipids, bile acids, and uremic toxins.

Retrospective study of cardiovascular disease risk factors among a cohort of combat veterans with lower limb amputation.

Introduction: Previous studies have shown that veterans with lower limb amputation have a higher risk for cardiovascular disease (CVD) compared with population-based controls. American veterans who have served in Iraq and Afghanistan with lower limb amputation may be at a similarly higher risk.

Patients And Methods: The Navel Health Research Center (NHRC) maintains the Expeditionary Medical Encounter Database (EMED) of military personnel who have sustained combat limb amputation or serious limb injury during the conflicts in Iraq and Afghanistan.

Clinic Use at the Departments of Defense and Veterans Affairs Following Combat Related Amputations.

Introduction: Little population-based research has described the transition from Department of Defense (DoD) to Department of Veterans Affairs (VA) healthcare following combat related amputations. The objectives were to describe (1) to what extent patients used either DoD only facilities, both DoD and VA facilities, or VA only facilities during the first 5 years postinjury, (2) which specific clinics were used and (3) clinic use among patients with different levels of amputation (upper versus lower), and among patients with early or late amputation.

Materials And Methods: This was a retrospective analysis of health data extracted from the expeditionary medical encounter database (EMED) and national DoD and VA databases.

A Retrospective Comparison of Five-Year Health Outcomes Following Upper Limb Amputation and Serious Upper Limb Injury in the Iraq and Afghanistan Conflicts.

Background: Limited population-based research has described long-term health outcomes following combat-related upper limb amputation.

Objective: To compare health outcomes following upper limb amputation with outcomes following serious upper limb injury during the first 5 years postinjury.

Design: Retrospective cohort.

The systems biology of uric acid transporters: the role of remote sensing and signaling.

Purpose Of Review: Uric acid homeostasis in the body is mediated by a number of SLC and ABC transporters in the kidney and intestine, including several multispecific 'drug' transporters (e.g., OAT1, OAT3, and ABCG2).

Correction: A Comparison of Four-Year Health Outcomes following Combat Amputation and Limb Salvage.

[This corrects the article DOI: 10.1371/journal.pone.

A Comparison of Four-Year Health Outcomes following Combat Amputation and Limb Salvage.

Little research has described the long-term health outcomes of patients who had combat-related amputations or leg-threatening injuries. We conducted retrospective analysis of Department of Defense and Department of Veterans Affairs health data for lower extremity combat-injured patients with (1) unilateral amputation within 90 days postinjury (early amputation, n = 440), (2) unilateral amputation more than 90 days postinjury (late amputation, n = 78), or (3) leg-threatening injuries without amputation (limb salvage, n = 107). Patient medical records were analyzed for four years postinjury.

An Organic Anion Transporter 1 (OAT1)-centered Metabolic Network.

There has been a recent interest in the broader physiological importance of multispecific "drug" transporters of the SLC and ABC transporter families. Here, a novel multi-tiered systems biology approach was used to predict metabolites and signaling molecules potentially affected by the in vivo deletion of organic anion transporter 1 (Oat1, Slc22a6, originally NKT), a major kidney-expressed drug transporter. Validation of some predictions in wet-lab assays, together with re-evaluation of existing transport and knock-out metabolomics data, generated an experimentally validated, confidence ranked set of OAT1-interacting endogenous compounds enabling construction of an "OAT1-centered metabolic interaction network.

Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling.

Background: In the setting of chronic kidney disease (CKD), altered extra-renal urate handling may be necessary to regulate plasma uric acid. The Remote Sensing and Signaling Hypothesis (Nigam S. What do drug transporters really do? Nat Rev Drug Discov 2015; 14: 29-44) suggests that multispecific solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters in different tissues are part of an inter-organ communication system that maintains levels of urate and other metabolites after organ injury.

Lower-limb amputation and effect of posttraumatic stress disorder on Department of Veterans Affairs outpatient cost trends.

Department of Veterans Affairs (VA) outpatient costs were analyzed for combat Veterans injured in Iraq and Afghanistan from 2001 to 2008. Patients had serious lower-limb injuries (n = 170) or unilateral (n = 460) or bilateral (n = 153) lower-limb amputation(s). Total costs over the follow-up period (2003 to 2012) and annual costs were analyzed.

Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters.

The proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.

Association of the ADRB2 (rs2053044) polymorphism and angiotensin-converting enzyme-inhibitor blood pressure response in the African American Study of Kidney Disease and Hypertension.

Aim/objectives/background: Hypertension is a risk factor for cardiovascular and kidney disease and is most prevalent in African-American adults. The renin-angiotensin-aldosterone system is integral in blood pressure regulation; angiotensin-converting enzyme inhibitors such as ramipril are first-line treatment options. As decreases in angiotensin result in catecholamine release, β-adrenergic receptor (ADRB) polymorphisms may influence blood pressure response to ramipril.

The organic anion transporter (OAT) family: a systems biology perspective.

The organic anion transporter (OAT) subfamily, which constitutes roughly half of the SLC22 (solute carrier 22) transporter family, has received a great deal of attention because of its role in handling of common drugs (antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs), toxins (mercury, aristolochic acid), and nutrients (vitamins, flavonoids). Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [Slc22a6, originally identified as NKT (novel kidney transporter)] and Oat3 (Slc22a8) knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease.

Glasgow Coma Scale scores, early opioids, and 4-year psychological outcomes among combat amputees.

Morphine and fentanyl are frequently used for analgesia after trauma, but there is debate over the advantages and disadvantages of these opioids. Among combat amputees, intravenous (IV) morphine (vs IV fentanyl) after injury was associated with reduced likelihood of posttraumatic stress disorder (PTSD). The previous results were based on military health diagnoses over 2 yr postinjury.

Association of phosphodiesterase 4 polymorphism (rs702553) with blood pressure in the African American Study of Kidney Disease and Hypertension Genomics Study.

Hypertension is a risk factor for diseases such as stroke, heart and kidney disease. Phosphodiesterase (PDE) enzymes play a significant role in regulating inflammation and there is some association between increased inflammatory cell mediators and development of hypertension. Previous research has shown the single nucleotide polymorphism (rs702553) on the PDE4D gene to be associated with stroke and carotid atherosclerosis.

Paraoxonase 1 (PON1) C/T-108 association with longitudinal mean arterial blood pressure.

Background: Blood pressure is a complex quantitative trait with a strong genetic component. In this study, we leveraged the Veterans Affairs electronic medical record system to explore the relationship between Paraoxonase 1 (PON1)-108 C/T (rs705379) and mean arterial blood pressure (MAP).

Methods: Outpatient blood pressure data over an approximate 8-year period was collected from the Veterans Affairs Hypertensive Cohort (N = 1,302).

Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC).

Background: Hyperhomocysteinemia is associated with increased venous thrombosis and cardiovascular disease (CVD). Mutations in the human methylenetetrahydrofolate reductase (MTHFR) gene have been associated with increased homocysteine levels and risks of CVD in various populations including those with kidney disease. Here, we evaluated the influence of MTHFR variants on progressive loss of kidney function.

Conformational changes of the multispecific transporter organic anion transporter 1 (OAT1/SLC22A6) suggests a molecular mechanism for initial stages of drug and metabolite transport.

The solute carrier (SLC) family of transporters play key roles in the movement of charged organic ions across the blood-urine, blood-cerebrospinal fluid, and blood-brain barriers and thus mediate the absorption, disposition, and elimination of many common pharmaceuticals (i.e., nonsteroidal anti-inflammatory drug (NSAIDs), antibiotics, and diuretics).