167,381 results match your criteria preclinical


Salivary parameters alterations after early exposure to environmental methylmercury: A preclinical study in offspring rats.

J Trace Elem Med Biol 2021 Jul 16;68:126820. Epub 2021 Jul 16.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Para, Belém, PA, Brazil. Electronic address:

Background: Methylmercury (MeHg) is still considered a global pollutant of major concern; thus, it becomes relevant to investigate and validate alternative diagnostic methods to track early-life human exposure. This study aimed to evaluate the salivary parameters and to characterize potential mechanisms of oxidative damage on the salivary glands (SG) of offspring rats after pre- and postnatal environmental-experimental MeHg exposure.

Methods: Pregnant Wistar rats were daily exposed to 40 μg/kg MeHg during both gestational and lactation periods. Read More

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Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Shoulder: An Orthoregeneration Network (ON) Foundation Review.

Arthroscopy 2021 Jul 19. Epub 2021 Jul 19.

Midwest Orthopaedics at Rush, Chicago, IL, USA. Electronic address:

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Read More

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Anti-microbial antibody response is associated with future onset of Crohn's disease independent of biomarkers of altered gut barrier function, subclinical inflammation, and genetic risk.

Gastroenterology 2021 Jul 19. Epub 2021 Jul 19.

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: /Aim: Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDR) of CD patients is an independent risk factor for future CD development.

Methods: We measured host serum antibody response to six microbial antigens at enrollment (Prometheus ELISA test: ASCA IgA/IgG, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS). Read More

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Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.

PLoS One 2021 22;16(7):e0255179. Epub 2021 Jul 22.

Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand.

Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-proliferative effect of COL17 on breast cancer cell through mTOR deactivation. Read More

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Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models.

J Clin Invest 2021 Jul 22. Epub 2021 Jul 22.

Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, United States of America.

Alcohol use disorder (AUD) is associated with substantial morbidity, mortality, and societal cost, and pharmacological treatment options for AUD are limited. The endogenous cannabinoid (eCB) signaling system is critically involved in reward processing and alcohol intake is positively correlated with release of the eCB ligand 2-Arachidonoylglycerol (2-AG) within reward neurocircuitry. Here we show that genetic and pharmacological inhibition of diacylglycerol lipase (DAGL), the rate limiting enzyme in the synthesis of 2-AG, reduces alcohol consumption in a variety of preclinical models ranging from a voluntary free-access model to aversion resistant-drinking and dependence-like drinking induced via chronic intermittent ethanol vapor exposure in mice. Read More

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Replenishment of TCA cycle intermediates provides photoreceptor resilience against neurodegeneration during progression of retinitis pigmentosa.

JCI Insight 2021 Jul 22. Epub 2021 Jul 22.

Department of Ophthalmology, UT Southwestern Medical Center, Dallas, United States of America.

The metabolic environment is important for neuronal cells, such as photoreceptors. When photoreceptors undergo degeneration, as occurs during retinitis pigmentosa (RP), patients have progressive loss of vision that proceeds to full blindness. Currently, there are no available treatments for the majority of RP diseases. Read More

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Therapeutic challenges at the preclinical level for targeted drug development for -associated cholangiocarcinoma.

Expert Opin Investig Drugs 2021 Jul 22:1-22. Epub 2021 Jul 22.

Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen Thailand.

Introduction: Cholangiocarcinoma (CCA) is a malignant tumor of bile duct epithelium with the highest incidence found in Thailand. Some patients are considered suitable for adjuvant therapy and surgical resection is currently the curative treatment for CCA patients. Tumor recurrence is still a hurdle after treatment; hence, finding novel therapeutic strategies to combat CCA is necessary for improving outcome for patients. Read More

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Lung ultrasound features and relationships with respiratory mechanics of evolving BPD in preterm rabbits and human neonates.

J Appl Physiol (1985) 2021 Jul 22. Epub 2021 Jul 22.

Division of Pediatrics and Neonatal Critical Care, "A.Béclère" Medical Centre, Paris Saclay University Hospitals, APHP, Paris, France.

Evolving broncho-pulmonary dysplasia (BPD) is a regionally heterogeneous disorder characterized by impaired alveolarization leading to lung aeration inhomogeneities. Hyperoxia-exposed preterm rabbits have been proposed to mimic evolving BPD and we aim to verify if this model has the same lung ultrasound and mechanical features of evolving BPD in human neonates. Twenty-five preterm rabbits and twenty-five neonates with evolving BPD were enrolled and subjected to semi-quantitative lung ultrasound and lung mechanics measurement. Read More

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Modular Platform for the Development of Recombinant Hemoglobin Scavenger Biotherapeutics.

Mol Pharm 2021 Jul 22. Epub 2021 Jul 22.

Division of Internal Medicine, Universitätsspital and University of Zurich, Zurich 8091, Switzerland.

Cell-free hemoglobin (Hb) is a driver of disease progression in conditions with intravascular or localized hemolysis. Genetic and acquired anemias or emergency medical conditions such as aneurysmal subarachnoid hemorrhage involve tissue Hb exposure. Haptoglobin (Hp) captures Hb in an irreversible protein complex and prevents its pathophysiological contributions to vascular nitric oxide depletion and tissue oxidation. Read More

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Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme.

J Med Chem 2021 Jul 22. Epub 2021 Jul 22.

IACS (Institute for Applied Cancer Science), University of Texas, MD Anderson Cancer Center, 1881 East Road, Houston, Texas 77054, United States.

Indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme that mediates the rate-limiting step in the metabolism of l-tryptophan to kynurenine, has been widely explored as a potential immunotherapeutic target in oncology. We developed a class of inhibitors with a conformationally constrained bicyclo[3.1. Read More

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Clinical Study on Plant Galactagogue Worldwide in Promoting Women's Lactation: a Scoping Review.

Plant Foods Hum Nutr 2021 Jul 22. Epub 2021 Jul 22.

Medical Biotechnology Laboratory, Central Research Laboratories, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.

Human milk is recommended by the World Health Organization (WHO) for the general well-being of infants. However, many mothers face an insufficient milk supply to breastfeed their children. Galactagogue, in particular, plant galactagogue, serves as a method to promote lactation. Read More

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Fatty acid profile in the breast and thigh muscles of the slow- and fast-growing birds under the same management system.

Trop Anim Health Prod 2021 Jul 22;53(4):409. Epub 2021 Jul 22.

Department of Theriogenology and Animal Production, Faculty of Veterinary Medicine, Usmanu Danfodiyo University Sokoto, Sokoto, Nigeria.

The aim of the study was to assess the effect of feeding the same diet to different breeds of chickens and at different ages on fatty acid (FA) composition of the breast and thigh muscles. A total of 150 chickens comprising 50 each of red jungle fowl (RJ) and village chicken (VC), the slow-growing birds, and the commercial broiler (CB), fast-growing birds, were used for this study. Ten chickens from each breed were serially euthanized at days 1, 10, 20, 56, and 120 post hatch, and pectoralis major and bicep femoris were harvested to represent the breast and thigh muscles respectively. Read More

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Amino acid metabolism as a therapeutic target in cancer: a review.

Amino Acids 2021 Jul 22. Epub 2021 Jul 22.

Faculty of Health and Life Sciences, University of the West of England, Coldharbour Lane, Bristol, BS16 1QY, UK.

Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for amino acids (AAs), which often results in a dependency on exogenous sources of AAs or requires upregulation of de novo synthesis. Read More

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Preclinical and clinical study on [F]DRKXH1: a novel β-amyloid PET tracer for Alzheimer's disease.

Eur J Nucl Med Mol Imaging 2021 Jul 22. Epub 2021 Jul 22.

Department of Nuclear Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1665, Kongjiang Street, Yangpu District, Shanghai, 200092, China.

Background: The deposition of β-amyloid (Aβ) in the brain is a biomarker of Alzheimer's disease (AD). Highly sensitive Aβ positron emission tomography (PET) imaging plays an essential role in diagnosing and evaluating the therapeutic effects of AD.

Aim: To synthesize a new Aβ tracer [F]DRKXH1 (5-(4-(6-(2-[18]fluoroethoxy)ethoxy)imidazo[1,2-alpha]pyridin-2-yl)phenyl) and evaluate the tracer performance by biodistribution analysis, in vivo small-animal PET-CT dynamic scan, ex vivo and in vitro autoradiography, and PET in human subjects. Read More

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Efficacy and Cost-effectiveness of Promotion Methods to Recruit Participants to an Online Screening Registry for Alzheimer Disease Prevention Trials: Observational Study.

J Med Internet Res 2021 Jul 22;23(7):e26284. Epub 2021 Jul 22.

Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Web-based screening may be suitable for identifying individuals with presymptomatic latent diseases for recruitment to clinical studies, as such people do not often visit hospitals in the presymptomatic stage. The promotion of such online screening studies is critical to their success, although it remains uncertain how the effectiveness of such promotion can differ, depending on the different promotion methods, domains of interest, or countries of implementation.

Objective: The Japanese Trial-Ready Cohort (J-TRC) web study is our ongoing online screening registry to identify individuals with presymptomatic Alzheimer disease (AD), aimed at facilitating the clinical trials for AD prevention. Read More

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Coupling relationship between glucose and oxygen metabolisms to differentiate preclinical Alzheimer's disease and normal individuals.

Hum Brain Mapp 2021 Jul 22. Epub 2021 Jul 22.

Key Laboratory of Specialty Fiber Optics and Optical Access Networks, Joint International Research Laboratory of Specialty Fiber Optics and Advanced Communication, School of Communication and Information Engineering, Shanghai University, Shanghai, China.

The discovery of preclinical Alzheimer's disease (preAD) provides a wide time window for the early intervention of AD. The coupling relationships between glucose and oxygen metabolisms from hybrid PET/MRI can provide complementary information on the brain's physiological state for preAD. In this study, we purpose to explore the change of coupling relationship among 27 normal controls (NCs), 20 preADs, and 15 cognitive impairments (CIs). Read More

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Lack of knowledge regarding HPV and its relation to oropharyngeal cancer among medical students.

Cancer Rep (Hoboken) 2021 Jul 22:e1517. Epub 2021 Jul 22.

Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan.

Background: Oropharyngeal cancer (OPC) is an important cause of cancer-related mortality. Early detection of OPC results in a favorable prognosis and higher survival rates. Infection by high-risk types of human papillomavirus (HPV) is a risk factor for OPC with an upward trend globally. Read More

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Omega-3 phospholipids and obesity-associated NAFLD: Potential mechanisms and therapeutic perspectives.

Eur J Clin Invest 2021 Jul 22:e13650. Epub 2021 Jul 22.

Laboratory of Adipose Tissue Biology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.

Prevalence of non-alcoholic fatty liver disease (NAFLD) increases in line with obesity and type 2 diabetes, and there is no approved drug therapy. Polyunsaturated fatty acids of n-3 series (omega-3) are known for their hypolipidemic and anti-inflammatory effects. Existing clinical trials suggest varying effectiveness of triacylglycerol- or ethyl ester-bound omega-3 in the treatment of NAFLD, without affecting advanced stages such as non-alcoholic steatohepatitis. Read More

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Cannabinoid receptor type 1 antagonists alter aspects of risk/reward decision making independent of toluene-mediated effects.

Psychopharmacology (Berl) 2021 Jul 22. Epub 2021 Jul 22.

Department of Neuroscience, Medical University of South Carolina, MSC 861, 30 Courtenay Drive, Charleston, SC, 29425-5712, USA.

Drugs of abuse including cannabis and inhalants impair risk/reward decision making. Cannabis use is often concurrent with inhalant intoxication; yet, preclinical studies investigating the role of endocannabinoids in inhalant misuse are limited. To address this gap in the literature, we used the well-validated probabilistic discounting task to assess risk/reward decision making in rodents following combinations of toluene vapor (a common inhalant) and manipulations of cannabinoid receptor type 1 (CB1R) signaling. Read More

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Dynamic Routing Capsule Networks for Mild Cognitive Impairment Diagnosis.

Med Image Comput Comput Assist Interv 2019 10;2019:620-628. Epub 2019 Oct 10.

Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that could cause severe cognitive damage to the patients. Diagnosis of AD at its preclinical stage, i.e. Read More

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October 2019

KSI-301: antibody biopolymer conjugate in retinal disorders.

Ther Adv Ophthalmol 2021 Jan-Dec;13:25158414211027708. Epub 2021 Jul 12.

Retina Services, JB Eye Care & Retina Centre, Salem, India.

KSI-301 is a new intravitreal anti-vascular endothelial growth factor (VEGF) antibody biopolymer conjugate under investigation for the treatment of age-related macular degeneration (AMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). Preclinical and early clinical trials so far have shown promising results in retinal vascular diseases. When using anti-VEGF agents for treatment of retinal disorders, the frequency of injections and follow-up visits has increased the treatment burden, greatly affecting the treatment outcome. Read More

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Development and validation of a mouse model of contemporary cannabis smoke exposure.

ERJ Open Res 2021 Jul 19;7(3). Epub 2021 Jul 19.

Dept of Medicine, McMaster University, Hamilton, ON, Canada.

Cannabis is widely used for both recreational and medicinal purposes. Inhalation of combusted cannabis smoke is the most common mode of drug consumption, exposing the lungs to the pharmacologically active ingredients, including tetrahydrocannabinol (THC) and cannabidiol (CBD). While the relationship between cannabis smoke exposure and compromised respiratory health has yet to be sufficiently defined, previous investigations suggest that cannabis smoke may dysregulate pulmonary immunity. Read More

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Registered Influenza Viral Vector Based Vaccine for Cattle in Kazakhstan: Age-Wise Safety and Efficacy Studies.

Front Cell Infect Microbiol 2021 1;11:669196. Epub 2021 Jul 1.

International Center for Vaccinology, Kazakh National Agrarian University (KazNAU), Almaty, Kazakhstan.

A novel influenza viral vector based vaccine (Flu-BA) was introduced for use in cattle in Kazakhstan in 2019. In this study, the safety and efficacy of the vaccine was evaluated in male and female cattle at different ages, and during pregnancy as a part of its registration process. Our data demonstrated that the Flu-BA vaccine was safe after prime or booster vaccination in calves (5-7 months old male and female), heifers (15-17 months old) and cows (6-7 years old) and was not abortogenic in pregnant animals. Read More

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COVID-19: Lockdown and its impact on medical students: A cross sectional study from a medical school in Mauritius.

Nepal J Epidemiol 2021 Jun 30;11(2):1006-1022. Epub 2021 Jun 30.

Department of geriatrics and longterm care, Rumailah Hospital, Doha, Qatar.

Background: The objectives of the study were to identify the psychological impacts of lockdown on medical students due to COVID-19 and to discover the educational perplexities being faced by these students during the lockdown.

Methods: A cross-sectional study was conducted at Sir Seewoosagur Ramgoolam Medical College (SSRMC), Mauritius. Questions were designed after an extensive review of the literature, so as to ensure relevance to meet the objectives of the study. Read More

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Antibody Subclass and Glycosylation Shift Following Effective TB Treatment.

Front Immunol 2021 5;12:679973. Epub 2021 Jul 5.

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, United States.

With an estimated 25% of the global population infected with (), tuberculosis (TB) remains a leading cause of death by infectious diseases. Humoral immunity following TB treatment is largely uncharacterized, and antibody profiling could provide insights into disease resolution. Here we focused on the distinctive TB-specific serum antibody features in active TB disease (ATB) and compared them with latent TB infection (LTBI) or treated ATB (txATB). Read More

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An Autonomous Cannabinoid System in Islets of Langerhans.

Front Endocrinol (Lausanne) 2021 5;12:699661. Epub 2021 Jul 5.

Laboratory of Clinical Investigation/Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.

While endocannabinoids (ECs) and cannabis were primarily studied for their nervous system effects, it is now clear that ECs are also produced in the periphery where they regulate several physiological processes, including energy storage, glucose and lipid metabolism, insulin secretion and synthesis, and hepatocyte function. Within islet of Langerhans there is an autonomous EC system (ECS). Beta (β)-cells contain all the enzymes necessary for EC synthesis and degradation; ECs are generated in response to cellular depolarization; their paracrine influence on β-cells is mostly through the cannabinoid 1 receptor (CBR) that is present on all β-cells; they modulate basal and glucose- and incretin-induced insulin secretion, and β-cell responses to various stressors. Read More

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Synergistic Activity of the HSP90 Inhibitor Ganetespib With Lapatinib Reverses Acquired Lapatinib Resistance in HER2-Positive Breast Cancer Cells.

Front Pharmacol 2021 5;12:651516. Epub 2021 Jul 5.

School of Pharmacy, Fujian Medical University, Fuzhou, China.

Lapatinib is an FDA-approved EGFR and HER2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer patients. However, its therapeutic efficacy is limited by primary or acquired resistance. In the present study, we established breast cancers cells with acquired lapatinib resistance and investigated the antitumor activity of the second-generation HSP90 inhibitor ganetespib in association with lapatinib in lapatinib-sensitive and -resistant cells. Read More

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Trichoderma reesei fungal degradation boosted the potentiality of date pit extract in fighting scopolamine-induced neurotoxicity in male rats.

Sci Rep 2021 Jul 21;11(1):14872. Epub 2021 Jul 21.

Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.

Date pits are nutritious by-products, containing high levels of indigestible carbohydrates and polyphenols. To maximize the biological effects of the active ingredients, the hard shell of the polysaccharide must be degraded. Therefore, the current study aimed to assess the protective potentials of date pits extract (DP) and fungal degraded date pits extract (FDDP) against scopolamine (SCO)-induced neurodegeneration in male rats. Read More

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IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer.

NPJ Breast Cancer 2021 Jul 21;7(1):95. Epub 2021 Jul 21.

Department of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, Sheffield, UK.

Breast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Read More

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Moral motivation regarding dementia risk testing among affected persons in Germany and Israel.

J Med Ethics 2021 Jul 21. Epub 2021 Jul 21.

Department of Community Mental Health, University of Haifa, Haifa, Israel.

Recent advances in biomarkers may soon make it possible to identify persons at high risk for late-onset Alzheimer's disease at a presymptomatic (preclinical) stage. Popular demand for testing is increasing despite the lack of cure and effective prevention options and despite uncertainties regarding the predictive value of biomarker tests. This underscores the relevance of the ethical, cultural and social implications of predictive testing and the need to advance the bioethical debate beyond considerations of clinical consequences. Read More

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