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[Anti-Aging - healthy aging].

Authors:
Thomas Münzer

Dtsch Med Wochenschr 2021 Apr 14;146(8):543-551. Epub 2021 Apr 14.

Anti-aging products still are a big business worldwide. The most active promoters of anti-aging products currently are internet dealers, the cosmetic and the dairy industry or companies that sell nutritional supplements. Only a few of the advertised substances however have been studied in clinical trials under robust conditions. Read More

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[Surgical treatment of urethral prolapse].

Aktuelle Urol 2021 Apr 14. Epub 2021 Apr 14.

Helios Krankenhaus St. Josefshospital, Klinik für Urologie und Kinderurologie, Krefeld Uerdingen.

Urethral prolapses in humans are rare. Urethral caruncula are more frequent. Caruncula originate from the dorsal external layer of the urethral meatus. Read More

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Teprotumumab: The Dawn of Therapies in Moderate-to-Severe Thyroid-Associated Ophthalmopathy.

Horm Metab Res 2021 Apr 14;53(4):211-218. Epub 2021 Apr 14.

Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.

Thyroid-associated ophthalmopathy (TAO) is a potentially sight-threatening ocular disease. About 3-5% of patients with TAO have severe disease with intense pain, inflammation, and sight-threatening corneal ulceration or compressive optic neuropathy. The current treatments of TAO are often suboptimal, mainly because the existing therapies do not target the pathogenesis of the disease. Read More

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Identification of three novel susceptibility loci for inflammatory bowel disease in Koreans in an extended genome-wide association study.

J Crohns Colitis 2021 Apr 14. Epub 2021 Apr 14.

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.

Background And Aims: Genome-wide association studies (GWAS) of inflammatory bowel disease (IBD) in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify 2 new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional data set of 1,726 cases and 378 controls. Read More

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Transition Services for Paediatric Inflammatory Bowel Disease; A Multicentre Study of Practice in the United Kingdom.

J Pediatr Gastroenterol Nutr 2021 Apr 12. Epub 2021 Apr 12.

Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton, UK Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK Department of Paediatric Gastroenterology, Sheffield Children's NHS Foundation Trust, Sheffield, UK Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UK Department of Paediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK Department of Paediatric Gastroenterology, The Royal Hospital for Sick Children, 9 Sciennes Rd, Edinburgh, UK Department of Paediatric Gastroenterology, Royal Hospital for Children Glasgow, 1345 Govan Road, Glasgow, UK Department of Paediatric Gastroenterology, Oxford University Hospitals, Oxford, UK Department of Paediatric Gastroenterology, Addenbrooke's Hospital, Cambridge, UK Department of Paediatric Gastroenterology, The Royal London Hospital, Barts Health NHS Trust, London, UK Department of Paediatric Gastroenterology, Alderhey Children's Hospital NHS Foundation Trust, West Derby, Eaton road, Liverpool L12 2AP,UK Department of Paediatric Gastroenterology, Birmingham Children's Hospital, Birmingham, UK Department of Paediatric Gastroenterology, St. Georges University Hospital NHS Foundation Trust, London, UK Department of Paediatric Gastroenterology, Chelsea and Westminster Hospital, 369 Fulham Road, London, UK Department of Paediatric Gastroenterology, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK Department of Paediatric Gastroenterology, University Hospitals of North Staffordshire NHS Trust, Stoke-On-Trent, UK Department of Paediatric Gastroenterology, Leeds Children's Hospital, Leeds Teaching Hospitals NHS trust, Leeds, UK Department of Paediatric Gastroenterology, Manchester Children's Hospital, Manchester, UK Department of Paediatric Gastroenterology, Nottingham Children's Hospital, Queens Medical Centre, Nottingham, UK Department of Paediatric Gastroenterology, University Hospitals of Leicester NHS Trust, Leicester, UK Department of Paediatric Gastroenterology, Evelina London Children's Hospital, UK.

Objectives: Patients with paediatric inflammatory bowel disease (IBD) constitute one of the largest cohorts requiring transition from paediatric to adult services. Standardised transition care improves short and long-term patient outcomes. This study aimed to detail the current state of transition services for IBD in the United Kingdom (UK). Read More

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Thyroid Dysfunction in Ménière's Disease: A Comprehensive Review.

ORL J Otorhinolaryngol Relat Spec 2021 Apr 14:1-8. Epub 2021 Apr 14.

Department of Otolaryngology, Head and Neck Surgery, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA.

Introduction: The precise etiology of Ménière's disease (MD) remains unknown; however, given the association of MD with serum antibodies and human leukocyte antigen (HLA) complex, several studies have proposed a relationship between MD and thyroid disorders. Similarly, multiple hypotheses exist regarding the metabolic disturbances of fluctuating thyroid hormone as a potential contributing agent in the development of MD.

Methods: A total of 171 abstracts were identified and screened by 2 independent reviewers. Read More

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Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy.

Nephron 2021 Apr 14:1-11. Epub 2021 Apr 14.

Section of Nephrology, Division of Internal Medicine, The University of Texas at MD Anderson Cancer Center, Houston, Texas, USA.

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Read More

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Frontiers of graphene-based Hall-effect sensors.

J Phys Condens Matter 2021 Apr 14. Epub 2021 Apr 14.

Department of Physics, University of Bath, Claverton Down, Bath, BA2 7AY, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.

Hall sensors have become one of the most used magnetic sensors in recent decades, performing the vital function of providing a magnetic sense that is naturally absent in humans. Various electronic applications have evolved from circuit-integrated Hall sensors due to their low cost, simple linear magnetic field response, ability to operate in a large magnetic field range, high magnetic sensitivity and low electronic noise, in addition to many other advantages. Recent developments in the fabrication and performance of graphene Hall devices promise to open up the realm of Hall sensor applications by not only widening the horizon of current uses through performance improvements, but also driving Hall sensor electronics into entirely new areas. Read More

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Risk factors for loss to follow-up of persons who inject drugs enrolled at syringe services programs in Kentucky.

Int J Drug Policy 2021 Apr 10;95:103255. Epub 2021 Apr 10.

KADAP Income Reinvestment Program (KIRP), Division of Infectious Diseases, University of Kentucky, United States.

Background: Syringe services programs (SSP) are an effective strategy to reduce blood-borne infections of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in persons who inject drugs (PWID). The objectives of this study were to determine the frequency and risk factors for loss to follow-up (LTFU) in PWID enrolled at SSPs in Kentucky.

Methods: A retrospective cohort study was conducted which included data of PWID enrolled at 32 SSP. Read More

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Effect of rare coding variants of charged amino acid residues on the function of human organic anion transporting polypeptide 1B3 (SLCO1B3).

Biochem Biophys Res Commun 2021 Apr 11;557:1-7. Epub 2021 Apr 11.

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu, 215123, China. Electronic address:

Human organic anion transporting polypeptide 1B3 (OATP1B3, gene symbol SLCO1B3) is a liver-specific uptake transporter. Its function was reported to be largely affected by some positively charged amino acid residues. However, so far the effect of naturally occurring genetic variants of charged residues on OATP1B3's function has not been explored yet. Read More

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Energy metabolism disorder mediated ammonia gas-induced autophagy via AMPK/mTOR/ULK1-Beclin1 pathway in chicken livers.

Ecotoxicol Environ Saf 2021 Apr 11;217:112219. Epub 2021 Apr 11.

College of Animal Science and Technology, Northeast Agricultural University, NO. 600 Chang Jiang Road, Xiang Fang District, Harbin 150030, China. Electronic address:

Ammonia gas is a well-known environmental pollution gas, threatening human health. Ammonia gas is also one of the most harmful gases to livestock and poultry for many years. Many studies have demonstrated toxic effect of ammonia gas on animal health, such as eyes, respiratory system, and digestive system. Read More

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A perspective essay on the use of Ga as a proxy for Fe in bioinorganic model studies and its successful use for therapeutic purposes.

J Inorg Biochem 2021 Mar 20;219:111411. Epub 2021 Mar 20.

Department of Chemistry, East Carolina University, Greenville, NC 27858, USA.

The use of Ga as a structural mimic for Fe in model bioinorganic investigations is usually based on a common assumption that Ga and Fe should form bioligand complexes of similar stabilities due to their similar charge/radius ratio (z/r). However, the literature survey presented here is contrary to this notion, showing that under laboratory conditions often Ga forms weaker bioligand complexes than Fein aqueous medium. We hypothesize that this is because Ga is more aquaphilic than Fe as suggested by their relative heats of hydration (ΔH). Read More

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Age dependency and lateralization in the three branches of the human superior longitudinal fasciculus.

Cortex 2021 Mar 15;139:116-133. Epub 2021 Mar 15.

Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, Osaka University, Suita, Japan; Graduate School of Frontier Biosciences, Osaka University, Suita, Japan. Electronic address:

The superior longitudinal fascicle/fasciculus (SLF) is a major white matter tract connecting the frontal and parietal cortices in humans. Although the SLF has often been analyzed as a single entity, several studies have reported that the SLF is segregated into three distinct branches (SLF I, II, and III). They have also reported the right lateralization of the SLF III volume and discussed its relationship with lateralized cortical functions in the fronto-parietal network. Read More

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Synthesis and structure-activity relationship study of novel 3-diethoxyphosphorylfuroquinoline-4,9-diones with potent antitumor efficacy.

Eur J Med Chem 2021 Apr 3;219:113429. Epub 2021 Apr 3.

Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Łódź, Poland. Electronic address:

Herein we report an efficient synthesis of a series of regioisomeric N,O-syn and N,O-anti 3-diethoxyphosphorylfuroquinoline-4,9-diones combining furoquinoline-5,8-dione skeleton, present in several highly cytotoxic compounds, with diethoxyphosphoryl moiety. The cytotoxic activity of the obtained analogs was tested against two human cancer cell lines: promyelocytic leukemia HL-60 and breast cancer adenocarcinoma MCF-7 and for comparison on human umbilical vein endothelial cells HUVEC and mammary gland/breast MCF-10 A cells. Several diethoxyphosphorylfuroquinoline-4,9-diones proved to be highly cytotoxic for cancer cells with IC values even below 0. Read More

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Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection.

Immunol Lett 2021 Apr 11. Epub 2021 Apr 11.

Instituto Nacional de Enfermedades Respiratorias, Centro de Investigación en Enfermedades Infecciosas, México City, Mexico.

Background: The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.

Objectives: We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. Read More

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Translation of single-cell transcriptomic analysis of uveal melanomas to clinical oncology.

Prog Retin Eye Res 2021 Apr 11:100968. Epub 2021 Apr 11.

University Côte d'Azur, France; Inserm, Biology and Pathologies of Melanocytes, Team1, Equipe Labellisée Ligue 2020 and Equipe Labellisée ARC 2019, Centre Méditerranéen de Médecine Moléculaire, Nice, France. Electronic address:

Uveal melanoma (UM) is an aggressive and deadly neoplasm. In recent decades, great efforts have been made to obtain a more comprehensive understanding of genetics, genomics and molecular changes in UM, enabling the identification of key cellular processes and signalling pathways. Still, there is no effective treatment for the metastatic disease. Read More

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DNA METHYLATION AS A KEY EPIGENETICS PLAYER FOR HEPATOBLASTOMA CHARACTERIZATION.

Clin Res Hepatol Gastroenterol 2021 Apr 11:101684. Epub 2021 Apr 11.

Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address:

Background: Hepatoblastoma (HB) is a rare embryonal liver tumor of children. Although intrinsic biological differences between tumors can affect prognosis, few groups have studied these differences. Given the recent increased attention to epigenetic mechanisms in the genesis and progression of these tumors, we aimed to classify HB samples according to the stages of liver development and DNA methylation machinery. Read More

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An efficient system to generate truncated human angiotensin converting enzyme 2 (hACE2) capable of binding RBD and Spike protein of SARS-CoV2.

Protein Expr Purif 2021 Apr 11:105889. Epub 2021 Apr 11.

Department of Biochemistry, Cancer Institute of the Second Affiliated Hospital (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), School of Medicine, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Human angiotensin converting enzyme 2 (hACE2) mediates the cell entry of both SARS-CoV and SARS-CoV2 and can be used as a drug target. The DNA encoding the truncated hACE2 (30-356aa) was cloned into pET-28a (+) and expressed in Escherichia coli Rosetta (DE3). The recombinant hACE2 (rhACE2) was purified by affinity chromatography on a Ni-NTA column and characterized with SDS-PAGE and Western blot. Read More

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Proof of Concept Efficacy Study of Intranasal Stabilized Isoamyl Nitrite (SIAN) in Rhesus Monkeys against Acute Cyanide Poisoning.

Regul Toxicol Pharmacol 2021 Apr 11:104927. Epub 2021 Apr 11.

Emergent BioSolutions, Inc., 300 Professional Drive, Gaithersburg, MD, 20879, US.

Cyanide is a fast-acting toxicant that inhibits aerobic cellular respiration in mitochondria. Historically, amyl nitrite has been used to treat cyanide poisoning. The objective of this study was to demonstrate the effectiveness of intranasal (IN) administration of stabilized isoamyl nitrite (SIAN) against lethal potassium cyanide (KCN) intravenous (IV) challenge in a conscious nonhuman primate (NHP) model. Read More

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Association between hippocampal structure and serum brain-derived neurotrophic factor (BDNF) in healthy adults: A registered report.

Neuroimage 2021 Apr 11:118011. Epub 2021 Apr 11.

Research Group "Social Stress and Family Health", Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Institute of Psychosocial Medicine, Psychotherapy and Psychooncology, Jena University Hospital, Friedrich Schiller University, Jena, Germany.

The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). Read More

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Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval.

Neuroimage 2021 Apr 11:118039. Epub 2021 Apr 11.

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria. Electronic address:

Animal studies using selective serotonin reuptake inhibitors (SSRIs) and learning paradigms demonstrated that serotonin is important for flexibility in executive functions and learning. SSRIs might facilitate relearning through neuroplastic processes and thus exert their clinical effects in psychiatric diseases where cognitive functioning is affected. However, translation of these mechanisms to humans is missing. Read More

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Cost-efficiency trade-offs of the human brain network revealed by a multiobjective evolutionary algorithm.

Neuroimage 2021 Apr 11:118040. Epub 2021 Apr 11.

Department of Psychology, Sun Yat-sen University, Guangzhou, China, 510006. Electronic address:

It is widely believed that the formation of brain network architecture is under the pressure of optimal trade-off between reducing wiring cost and promoting communication efficiency. However, the questions of whether this trade-off exists in empirical human brain structural networks and, if so, how it takes effect are still not well understood. Here, we employed a multiobjective evolutionary algorithm to directly and quantitatively explore the cost-efficiency trade-off in human brain structural networks. Read More

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C5aR inhibition of non-immune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia.

J Allergy Clin Immunol 2021 Apr 11. Epub 2021 Apr 11.

Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Austria. Electronic address:

Background: Excessive inflammation triggered by a hitherto undescribed mechanism is a hallmark of severe SARS-CoV-2 infections and is associated with enhanced pathogenicity and mortality.

Objective: Complement hyper activation promotes lung injury and was observed in patients suffering from MERS-CoV, SARS-CoV-1 and SARS-CoV-2 infections. Therefore, we investigated the very first interactions of primary human airway epithelial cells upon exposure to SARS-CoV-2 in terms of complement C3-mediated effects. Read More

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Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer.

Cell Stem Cell 2021 Apr 8. Epub 2021 Apr 8.

Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, the Netherlands; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands. Electronic address:

Cervical cancer is a common gynecological malignancy often caused by high-risk human papillomavirus. There is a paucity of human-derived culture systems to study the cervical epithelium and the cancers derived thereof. Here we describe a long-term culturing protocol for ecto- and endocervical epithelia that generates 3D organoids that stably recapitulate the two tissues of origin. Read More

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COVID-19 and children's health in the United States: consideration of physical and social environments during the pandemic.

Environ Res 2021 Apr 11:111160. Epub 2021 Apr 11.

Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo NY, 14214.

Public health measures necessary to counteract the coronavirus disease 2019 (COVID-19) pandemic have resulted in dramatic changes in the physical and social environments within which children grow and develop. As our understanding of the pathways for viral exposure and associated health outcomes in children evolves, it is critical to consider how changes in the social, cultural, economic, and physical environments resulting from the pandemic could affect the development of children. This review article considers the environments and settings that create the backdrop for children's health in the United States during the COVID-19 pandemic, including current threats to child development that stem from: A) change in exposures to environmental contaminants such as heavy metals, pesticides, disinfectants, air pollution and the built environment; B) changes in food environments resulting from adverse economic repercussion of the pandemic and limited reach of existing safety nets; C) limited access to children's educational and developmental resources; D) changes in the social environments at the individual and household levels, and their interplay with family stressors and mental health; E) social injustice and racism. Read More

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Reducing acetylated tau is neuroprotective in brain injury.

Cell 2021 Apr 10. Epub 2021 Apr 10.

Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Weill Cornell Autism Research Program, Weill Cornell Medicine of Cornell University, New York, NY, USA; Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, OH, USA. Electronic address:

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Read More

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The anterior cingulate cortex directs exploration of alternative strategies.

Neuron 2021 Apr 7. Epub 2021 Apr 7.

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Electronic address:

The ability to adjust one's behavioral strategy in complex environments is at the core of cognition. Doing so efficiently requires monitoring the reliability of the ongoing strategy and, when appropriate, switching away from it to evaluate alternatives. Studies in humans and non-human primates have uncovered signals in the anterior cingulate cortex (ACC) that reflect the pressure to switch away from the ongoing strategy, whereas other ACC signals relate to the pursuit of alternatives. Read More

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The IMPACT trial: human papillomavirus, cervical cytology and histopathological results from the baseline and 1-year follow-up phase.

Am J Obstet Gynecol 2021 Apr 11. Epub 2021 Apr 11.

Ventana Medical Systems Inc./Roche Tissue Diagnostics, Tucson, AZ.

Background: An increase in human papillomavirus (HPV) test volumes is expected in the near future as HPV-based screening protocols are expected to become more broadly adopted.

Objective: The IMproving Primary screening And Colposcopy Triage (IMPACT) trial, a prospective, multicenter US cervical cancer screening trial, was conducted to obtain FDA approvals for the new high-throughput cobas HPV for use on the cobas 6800/8800 Systems (cobas HPV) for detecting cervical precancer and cancer (cervical intraepithelial neoplasia of grade 2 or worse [≥CIN2] and grade 3 or worse, [≥CIN3]). Here the baseline demographics, HPV, cervical cytology and histolpathologic results are presented. Read More

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