5,510 results match your criteria Pick Disease


Recognition of pre-hypertrophic cardiac involvement in Fabry Disease based on automated electrocardiographic measures.

Int J Cardiol 2021 Jun 19. Epub 2021 Jun 19.

Institute of Health and Wellbeing, University of Glasgow, Scotland, United Kingdom.

Background: Various electrocardiographic (ECG) indices have been shown to be useful for early recognition and staging of cardiac involvement in Fabry Disease (FD). However, many of them lack acceptable sensitivity and specificity. We assessed the value of automated ECG measures to discriminate between pre-hypertrophic FD and healthy individuals. Read More

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Inhibition of Histone Deacetylases 1, 2, and 3 Enhances Clearance of Cholesterol Accumulation in Niemann-Pick C1 Fibroblasts.

ACS Pharmacol Transl Sci 2021 Jun 27;4(3):1136-1148. Epub 2021 May 27.

Department of Biochemistry, Weill Cornell Medical College, New York, New York 10065, United States.

Niemann-Pick disease type C1 (NPC1) is a rare genetic cholesterol storage disorder caused by mutations in the gene. Mutations in this transmembrane late endosome protein lead to loss of normal cholesterol efflux from late endosomes and lysosomes. It has been shown that broad spectrum histone deacetylase inhibitors (HDACi's) such as Vorinostat correct the cholesterol accumulation phenotype in the majority of NPC1 mutants tested in cultured cells. Read More

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Longitudinal Data in Patients with Niemann-Pick Type C Disease Under Combined High Intrathecal and Low Intravenous Dose of 2-hydroxylpropyl-β-cyclodextrin.

Innov Clin Neurosci 2021 Jan-Mar;18(1-3):11-16. Epub 2021 Jan 1.

Drs. Bountouvi, Giorgi, Papadopoulou, Tsirouda, Fryganas, Spanou, Georgaki, Asprogeraka, and Dinopoulos are with the Third Department of Pediatrics, Athens University Medical School, at the University General Hospital "Attikon" in Athens, Greece.

Niemann-Pick Type C disease (NPC) is a rare, incurable, autosomal-recessive, lysosomal storage disorder with protean and progressive neurovisceral manifestations characterized by accumulation of intracellular unesterified cholesterol. The investigational use of 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) in the treatment of NPC has shown promising results in improving life expectancy and reducing neurological damage in this patient population. This case report describes two children with the neurological form of NPC: a 5-year-old male patient in advanced stage of the disease and an 11-year-old female patient in moderately advanced stage. Read More

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January 2021

Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case-control study.

Metab Brain Dis 2021 Jun 19. Epub 2021 Jun 19.

Melbourne Neuropsychiatry Centre, University of Melbourne, Parkville, Victoria, Australia.

Hippocampal brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippocampal complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippocampal subfields between NPC and healthy individuals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3 T T1-weighted MRI scan. Read More

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Gene Therapy Moves Forward for Niemann-Pick Disease Type C1.

Authors:
R Scott McIvor

Hum Gene Ther 2021 Jun;32(11-12):540

Department of Genetics, Cell Biology and Development, Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA.

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Hepatocellular carcinoma as a complication of Niemann-Pick disease type C1.

Am J Med Genet A 2021 Jun 17. Epub 2021 Jun 17.

Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Niemann-Pick disease type C (NPC) is a rare and fatal lysosomal storage disorder characterized by neurodegeneration and hepatic involvement. Mutations in either NPC1 or NPC2, two genes encoding lysosomal proteins, lead to an intracellular accumulation of unesterified cholesterol and sphingolipids in late endosomes/lysosomes. Early cholestatic disease is considered a hallmark of patients with early disease onset. Read More

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Structure of Tau filaments in Prion protein amyloidoses.

Acta Neuropathol 2021 Jun 14. Epub 2021 Jun 14.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) with a nonsense mutation in the PRNP gene that leads to early termination of translation of PrP (Q160Ter or Q160X), and Gerstmann-Sträussler-Scheinker (GSS) disease, with a missense mutation in the PRNP gene that leads to an amino acid substitution at residue 198 (F198S) of PrP. The clinical and neuropathologic phenotypes associated with these two mutations in PRNP are different; however, the neuropathologic analyses of these two genetic variants have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. Read More

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Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Front Neurosci 2021 28;15:673600. Epub 2021 May 28.

Department of Paediatrics, University Hospital Center Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia.

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes-MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis. Read More

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Development and validation of signature sequence-based PCR for improved molecular diagnosis of tuberculosis.

J Mol Diagn 2021 Jun 8. Epub 2021 Jun 8.

ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi. Electronic address:

Reliable, fast, and affordable diagnosis for TB remains a challenge to reduce disease incidence in resource-poor countries. Tests based on nucleotide sequences that are 'signature' to M. tuberculosis (M. Read More

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A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-β-cyclodextrin for acute liver disease in infants with Niemann-Pick C1.

Mol Genet Metab Rep 2021 Sep 26;28:100772. Epub 2021 May 26.

Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America.

Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in -lysosomal storage of unesterified cholesterol in the central nervous system and liver. Acute liver disease in the newborn period may be self-limited or fatal. 2-hydroxypropyl-β-cyclodextrin (2HPBCD) is a cholesterol-binding agent that reduces lysosomal cholesterol storage. Read More

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September 2021

Spatiotemporal Developmental Upregulation of Prestin Correlates With the Severity and Location of Cyclodextrin-Induced Outer Hair Cell Loss and Hearing Loss.

Front Cell Dev Biol 2021 24;9:643709. Epub 2021 May 24.

Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, United States.

2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Read More

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Naturally occurring anti-Kp in an infant with recurrent bacterial infection: A case report and review of the literature.

Vox Sang 2021 Jun 8. Epub 2021 Jun 8.

Department of Immunohematology & Blood Transfusion, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.

Naturally occurring anti-Kp antibody is extremely rare and was first reported in 1957, named after the first producer 'Penney'. However, the subsequent anti-Kp reports presented were all anti-Kp due to isoimmunization. Individuals with severe bacterial infections particularly Gram-negative bacteria are known to be capable of producing cross-reactive antibodies against Kell blood group system. Read More

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[Diffuse parenchymal lung diseases in Niemann-Pick disease type C2].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):519-521

Department of Pulmonology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.

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A cross-sectional, prospective ocular motor study in 72 patients with Niemann-Pick disease type C.

Eur J Neurol 2021 Jun 7. Epub 2021 Jun 7.

German Center for Vertigo and Balance Disorders and Department of Neurology, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University Munich, Germany.

Objective: To characterize ocular motor function in patients with Niemann-Pick type C (NPC).

Methods: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from twelve countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Read More

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Clinical and neuropathological diversity of tauopathy in MAPT duplication carriers.

Acta Neuropathol 2021 Jun 6. Epub 2021 Jun 6.

Normandie Univ, UNIROUEN, Inserm U1245, CHU Rouen, Department of Genetics and CNR-MAJ, F-76000, Rouen, France.

Microduplications of the 17q21.31 chromosomal region encompassing the MAPT gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Read More

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Prevalence of patients with lysosomal storage disorders and peroxisomal disorders: A nationwide survey in Japan.

Mol Genet Metab 2021 Jul 12;133(3):277-288. Epub 2021 May 12.

Advanced Clinical Research Center, Southern Tohoku Research Center for Neuroscience, Kanagawa, Japan.

Introduction: Lysosomal storage disorders and peroxisomal disorders are rare diseases caused by the accumulation of substrates of the metabolic pathway within lysosomes and peroxisomes, respectively. Owing to the rarity of these diseases, the prevalence of lysosomal storage disorders and peroxisomal disorders in Japan is unknown. Therefore, we conducted a nationwide survey to estimate the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. Read More

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Vertical saccadic palsy and foveal retinal thinning in Niemann-Pick disease type C.

PLoS One 2021 4;16(6):e0252825. Epub 2021 Jun 4.

Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.

Introduction: Niemann-Pick type C (NPC) is a lysosomal storage disease that is progressive and life-limiting, with an estimated incidence of 1:120,000 live births. In addition to systemic manifestation with (hepato-)splenomegaly, there are a number of neurological manifestations (ataxia, dysarthria, dementia, cataplexy, epileptic seizures, and psychiatric disorders). Characteristic is vertical supranuclear gaze palsy, which is often overlooked. Read More

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Lipid-mediated impairment of axonal lysosome transport contributing to autophagic stress.

Autophagy 2021 Jun 4. Epub 2021 Jun 4.

Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.

Efficient degradation of autophagic vacuoles (AVs) generated at axon terminals by mature lysosomes enriched in the cell body represents an exceptional challenge that neurons face in maintaining cellular homeostasis. Here, we discuss our recent findings revealing a lipid-mediated impairment of lysosome transport to distal axons contributing to axonal AV accumulation in the neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NPC). Using transmission electron microscopy, we observed a striking buildup of endocytic and autophagic organelles in NPC dystrophic axons, indicating defects in the clearance of organelles destined for lysosomal degradation. Read More

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Engineered Human Monoclonal scFv to Receptor Binding Domain of .

Vaccines (Basel) 2021 May 4;9(5). Epub 2021 May 4.

Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

(1) Background: (EBOV) poses as a significant threat for human health by frequently causing epidemics of the highly contagious Ebola virus disease (EVD). EBOV glycoprotein (GP), as a sole surface glycoprotein, needs to be cleaved in endosomes to fully expose a receptor-binding domain (RBD) containing a receptor-binding site (RBS) for receptor binding and genome entry into cytoplasm for replication. RBDs are highly conserved among EBOV species, so they are an attractive target for broadly effective anti-EBOV drug development. Read More

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Three-Dimensional Imaging of Whole-Body Zebrafish Revealed Lipid Disorders Associated with Niemann-Pick Disease Type C1.

Anal Chem 2021 Jun 1;93(23):8178-8187. Epub 2021 Jun 1.

Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China.

Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. Read More

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TDP-43 proteinopathy occurs independently of autophagic substrate accumulation and underlies nuclear defects in Niemann-Pick C disease.

Neuropathol Appl Neurobiol 2021 May 28. Epub 2021 May 28.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.

Aims: Neuronal cytoplasmic inclusions of TAR-DNA binding protein of 43 kDa (TDP-43) are a pathological hallmark of diverse neurodegenerative disorders, yet the processes that mediate their formation and their functional significance remain incompletely understood. Both dysfunction in autophagy and neuroinflammation have been linked to TDP-43 mislocalisation. Here, we investigate TDP-43 proteinopathy in Niemann-Pick type C disease (NPC), an autosomal recessive lysosomal storage disease (LSD) distinguished by the accumulation of unesterified cholesterol within late endosomes and lysosomes. Read More

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Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion.

Exp Mol Med 2021 05 25;53(5):956-972. Epub 2021 May 25.

Center for Cognition and Sociality, Cognitive Glioscience Group, Institute for Basic Science, Daejeon, 34126, Republic of Korea.

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry. Read More

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Polyneuropathy following COVID-19 infection: the rehabilitation approach.

BMJ Case Rep 2021 May 24;14(5). Epub 2021 May 24.

Rehabilitation Medicine, Oxford Centre for Enablement, Oxford, UK.

A range of neurological manifestations associated with COVID-19 have been reported in the literature, but the pathogenesis of these have yet to be fully explained. The majority of cases of peripheral nervous system disease published thus far have shown a symmetrical pattern. In contrast, we describe the case of a patient with asymmetrical predominantly upper-limb sensorimotor polyneuropathy following COVID-19 infection, likely due to a multifactorial pathological process involving critical illness neuropathy, mechanical injury and inflammatory disease. Read More

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Enrichment of NPC1-deficient cells with the lipid LBPA stimulates autophagy, improves lysosomal function, and reduces cholesterol storage.

J Biol Chem 2021 May 20:100813. Epub 2021 May 20.

Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901 USA. Electronic address:

Niemann-Pick C (NPC) is an autosomal recessive disorder characterized by mutations in the NPC1 or NPC2 genes encoding endo-lysosomal lipid transport proteins, leading to cholesterol accumulation and autophagy dysfunction. We have previously shown that enrichment of NPC1-deficient cells with the anionic lipid lysobisphosphatidic acid (LBPA; also called bis(monoacylglycerol)phosphate, BMP) via treatment with its precursor phosphatidylglycerol (PG) results in a dramatic decrease in cholesterol storage. However, the mechanisms underlying this reduction are unknown. Read More

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Neuropsychological assessment in Niemann-Pick disease type C: a systematic review.

Neurol Sci 2021 May 22. Epub 2021 May 22.

IRCCS Centro Neurolesi "Bonino-Pulejo", S.S. 113, Contrada Casazza, 98124, Messina, Italy.

Background: The neuropsychological profile of Niemann-Pick type C (NP-C) patients is characterized by an early deterioration in executive functions and attention. There are few studies on cognitive impairment and on neuropsychological assessment of NP-C disease. The purpose of this review is to analyze the studies on a psychological assessment for NP-C patients. Read More

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Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

J Clin Oncol 2021 May 21:JCO2100605. Epub 2021 May 21.

Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.

Purpose: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.

Materials And Methods: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Read More

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NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes.

EMBO J 2021 May 21:e105990. Epub 2021 May 21.

Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.

Cholesterol and phosphoinositides (PI) are two critically important lipids that are found in cellular membranes and dysregulated in many disorders. Therefore, uncovering molecular pathways connecting these essential lipids may offer new therapeutic insights. We report that loss of function of lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade that alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle between Golgi-endoplasmic reticulum (ER), as well as lysosome-ER membrane contact sites (MCS). Read More

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Understanding what matters most to patients in acute care in seven countries, using the flash mob study design.

BMC Health Serv Res 2021 May 19;21(1):474. Epub 2021 May 19.

Department of Emergency Medicine, University Hospital Basel, Basel, Switzerland.

Background: Truly patient-centred care needs to be aligned with what patients consider important, and is highly desirable in the first 24 h of an acute admission, as many decisions are made during this period. However, there is limited knowledge on what matters most to patients in this phase of their hospital stay. The objective of this study was to identify what mattered most to patients in acute care and to assess the patient perspective as to whether their treating doctors were aware of this. Read More

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Preferences for pre-exposure prophylaxis among U.S. military men who have sex with men: results of an adaptive choice based conjoint analysis study.

Mil Med Res 2021 May 19;8(1):32. Epub 2021 May 19.

Yale School of Nursing, 400 West Campus Drive, Orange, CT, 06477, USA.

Background: Pre-exposure prophylaxis (PrEP) prevents human immunodeficiency virus (HIV) infection, but its use remains low among U.S. military men who have sex with men (MSM), likely due to mis-matching with personal preferences. Read More

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