Jul 1st, 2022 - The purpose of this protocol is to study the natural history of spondyloarthritis (SpA) in children and adults. Spondyloarthritis encompasses a spectrum of immune-mediated inflammatory diseases that exhibit overlapping features, but differ from other types of inflammatory arthritis in genetic predisposition, pathogenesis, and outcome. Ankylosing spondylitis (AS), the most common form of SpA, fr...

Jun 21st, 2022 - The hypothesis is that the addition of daratumumab administered SC to standard MM regimens will improve responses compared to response data observed in completed phase 3 studies without daratumumab. Disease evaluations will include measurements of myeloma proteins, bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected...

Jul 1st, 2022 - This is a phase I, single-site, dose escalation study to evaluate the safety, immunogenicity, and efficacy of the recombinant circumsporozoite protein (rCSP) antigen malaria vaccine administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)]. The study population will consist of 65 healthy male and female adults aged 18 to 45 years ...

Jul 1st, 2022 - Biosynthesis of proteins is essential for growth and continued maintenance of the entire neuron including axons, dendrites, and synaptic terminals, and it is clearly one of the important biochemical processes underlying adaptive changes in the nervous system. Studies in experimental animals with the quantitative autoradiographic L-[1-(14)C]leucine method have demonstrated a number of the physio...

Jul 1st, 2022 - Background: - Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered along with highdose aldesleukin (IL-2) following a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine. - Pembrolizumab, a monoclonal antibody that binds to PD-1 and blocks the P...

Jul 1st, 2022 - PRIMARY OBJECTIVES: Phase I: To determine the MTD (Maximum Tolerated Dose) and select optimal biological doses (OBD) of NT-I7 in HGG patients with severe lymphopenia Pilot Study: To test the effect of NT-I7 on CD4 counts compared to control SECONDARY OBJECTIVES: To evaluate the optimal biological dose of NT-I7 To evaluate the effect of concurrent dexamethasone To evaluate the duration of effect...

Jul 1st, 2022 - Background: Kaposi Sarcoma (KS) is a multicentric angioproliferative tumor that most frequently involves skin, but can also involve lymph nodes, lungs and gastrointestinal tract. It is most common in people with HIV or other forms of immune compromise. Patients with AIDS-associated KS have worse survival than HIV-infected patients without KS. Patients may present with advanced disease KS and/or...

Jul 1st, 2022 - Objective: The goal of this protocol is to understand how the pathology of multiple sclerosis (MS) relates to its evolution over time as observed through neuroradiological, clinical, and biological data collection in vivo. Study population: This study will enroll up to 150 individuals with MS, targeting 50 study completers, across various ages and stages of the disease, as well as 50 appropriat...

Jul 1st, 2022 - The lipoprotein transport system is vital to the delivery of the hydrophobic fats that are carried in the aqueous environment of the blood. The lipoprotein particles that comprise this system are polydisperse and contain triglycerides, free and esterified cholesterol, phospholipids and proteins. Inborn errors in the lipoprotein transport system lead to alterations in both the steady state conce...

Jul 1st, 2022 - Background: Phototoxicity is a sunburn-like response associated with certain medications and is a phenomenon which is not completely understood. Although clinically similar to a typical sunburn reaction, the gene expression changes in phototoxic skin reactions may differ from those in typical sunburn. Doxycycline is a relatively well-tolerated and known phototoxic antimicrobial which can be use...

Jul 1st, 2022 - The "Agricultural Health Study" (AHS) is a collaborative effort between the National Cancer Institute and the National Institute of Environmental Health Sciences. The U.S. Environmental Protection Agency and the National Institute for Occupational Safety and Health are providing support for a limited exposure assessment effort. Initial data collection on a prospective cohort of 89,655 study sub...

Jul 1st, 2022 - Uveitis refers to a large group of intraocular inflammatory diseases that can cause devastating visual loss in adults and children. This study establishes a clinical database and biospecimen repository for the identification of novel factors relevant to the pathogenesis, progression, and response to treatment of a wide spectrum of uveitic conditions. Objectives: This study provides for standard...

Jul 1st, 2022 - Background Children and young adults diagnosed with a high-grade or high-risk cancer (e.g., diffuse intrinsic pontine glioma, glioblastoma multiforme, relapsed-refractory leukemia, refractory metastatic sarcomas) face a poor prognosis given limited curative options. Recent research has indicated that this population of patients and their parents experience elevated stress and poorer health-rela...

Jul 1st, 2022 - The NIH provides a unique opportunity for research scientists to participate in the bench-to-bedside process, which is essential for the full implementation of translational medicine programs. The study of rare monogenetic and undiagnosed diseases is a complex bedside-to-bench-to-bedside endeavor. Recent studies show that rare genetic variants are more likely than common variants to have delete...

Jul 1st, 2022 - BACKGROUND: Our research group has made extensive use of ecological momentary assessment (EMA) to understand people s daily experiences with opioid craving, use, and lapse. We have also administered clinic-based psychotherapies such as cognitive-behavioral therapy (CBT), in which clients learn to avoid, escape, resolve, or reframe problems (such as stress) that can trigger lapses to drug use. C...

Jul 1st, 2022 - BACKGROUND: Endometrial cancer is the most common and second deadliest gynecological cancer in women in the United States, with over 63,000 new cases and 11,000 deaths expected to occur in 2018. Unlike most cancers, endometrial cancer incidence and mortality are increasing, due to increases in risk factors such as obesity and population aging. Racial disparities in endometrial cancer incidence ...

Jul 1st, 2022 - Despite data indicating nearly 80,000 individuals starting HIV pre-exposure prophylaxis (PrEP) by the end of 2015, the Centers for Disease Control and Prevention (CDC) estimates that there are over 1.2 million adults with a substantial risk for HIV acquisition. Therefore, only 6% of these individuals are receiving PrEP. One of the barriers to PrEP implementation is lack of healthcare provider (...

Jul 1st, 2022 - Study Design: This is the first study in healthy adults of the N6LS monoclonal antibody (MAb). It is a dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics (PK) of N6LS administered intravenously (IV) and subcutaneously (SC) to healthy adults. For SC administration, N6LS will be administered alone or coadministered with the permeation enhancer rHuPH20 enzyme. Primar...

Jul 1st, 2022 - The investigators refined research aim is to determine if a clinic-based collaborative care team, including a community health worker (CHW) to deliver community-based contextualized care, reduces disparities in blood pressure control rates, lowers cardiovascular disease (CVD) risk, and improves outcomes among patients with hypertension and other common comorbid conditions when compared to stand...

Jul 1st, 2022 - At present, there are no clear guidelines as to when antiretroviral therapy for human immunodeficiency virus (HIV) infection should be stopped in the setting of elevated liver enzymes. In large part, this is due to a limited understanding of the natural history of antiretroviral-related hepatotoxicity. Although several antiretrovirals have been reported to cause fatal acute hepatitis, more ofte...

Jul 1st, 2022 - Williams syndrome (WS) is a multisystem developmental disorder caused by deletion of 26-28 genes, including the elastin gene, located on chromosome 7q11.23. Cardiovascular disease in WS, including obstructive vascular disease and hypertension, and relatively mild skin changes are caused by the elastin gene deletion. Even though all WS subjects are missing one copy of this gene, the expression o...

Jul 1st, 2022 - Many of the complications of sickle cell disease, such as stroke, kidney damage, skin ulceration,pulmonary hypertension, and cardiac hypertrophy are prevented, delayed or reduced by inheritance of one of more deletions of the alpha globin genes. Our long-term research goal is to understand how deletions of alpha globin protect against the vascular complications of sickle cell disease. Deletions...

Jul 1st, 2022 - The Division of Intramural Population Health Research (DIPHR) will conduct a research study entitled: "Fetal Body Composition and Volumes Study" to catalog and perform 2 Dimensional (2D) and 3 Dimensional (3D) measurement of the obstetrical ultrasound images in the existing bank of singleton and twin gestations collected from the NICHD Fetal Growth Studies. The research study aims to augment th...

Jul 1st, 2022 - More than ever before, people are eating more calories from food than what they are burning off through exercise and other activities, and this imbalance is causing the rising rates of obesity and diabetes in the US and throughout the world. The different types of body fat are central players in this process. The white fat stores excess calories coming from food, while brown fat - also known as...

Jul 1st, 2022 - Objective This protocol is being performed to 1) study the natural history and disease pathogenesis in patients with tumor related epilepsy, 2) collect prospective data on seizure outcomes following standard surgical treatment of brain tumors with associated seizures2, 3) follow the clinical course of patients after surgical resection of brain tumors with associated seizures, such as outcomes i...

Jul 1st, 2022 - This is a natural history study that will examine craniofacial anomalies that affect the normal development of the facial skeleton, including birth defects and dentofacial developmental abnormalities that express themselves with the growth of the individual. Craniofacial anomalies may be rare and present at birth, such as hemifacial microsomia (1 in every 7500 live births), or common, such as d...

Jul 1st, 2022 - Previous studies have shown that the opioid receptor modulator nalmefene can reduce heavy drinking among alcoholics. Genetic variation at the micro-opioid receptor gene locus, OPRM1, specifically the A118G polymorphism, is associated with differential subjective responses to alcohol. Further, the A118G polymorphism has been shown to moderate the effect of opioid receptor modulators on alcohol c...

Jul 1st, 2022 - Background. ManNAc (N-acetyl D-mannosamine) is an uncharged monosaccharide that is the biologic precursor of N-acetyl neuraminic acid (Neu5Ac, sialic acid). Sialic acids are the negatively charged, terminal monosaccharides of carbohydrate chains that are attached to glycoproteins and glycolipids (glycans). Most glycans serve cellular signaling functions, and frequently appear on the cell surfac...

Jul 1st, 2022 - This is a screening protocol for healthy volunteers to participate in research studies conducted by Laboratory of Malaria Immunology and Vaccinology (LMIV). Malaria-related morbidity and mortality have a major economic impact in endemic regions and present a substantial health risk to non-immune travelers and people living in endemic areas. To stem the worldwide impact of this devastating disea...

Jul 1st, 2022 - Molecular genetics has the potential to revolutionize the diagnosis and treatment of inherited eye diseases. Progress in research on inherited eye disease would be augmented by the availability of patient DNA coupled to robust, anonymous phenotypic information. The National Ophthalmic Genotyping and Phenotyping Network (eyeGENE(R)) has been created to answer this need. By creating a national DN...

Jul 1st, 2022 - BACKGROUND: We previously conducted a retrospective cohort study of 12,193 patients evaluated for infertility between 1960-1988 at five clinical sites. Detailed information abstracted from the medical records, along with questionnaires administered to located patients and cancer incidence and mortality data derived from cancer registries and the National Death Index, allowed us to examine cance...

Jul 1st, 2022 - The prevalence of obesity in the United States has reached alarming proportions with 33% of adults over the age of 20 being overweight. In some populations, obesity is even more prevalent. Although there have been a number of advances in our understanding of the genetics of obesity, the environmental influences on the genetic expression of obesity requires further investigation. In an effort to...

Jul 1st, 2022 - The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic kidney disease. FIND is conducted in eleven centers and in many ethnic groups throughout the United States. Two different strategies are used to localize genes predisposing to kidney disease: a family-based genetic linkage/association study and a case-control ...

Jul 1st, 2022 - Childhood leukemia is the most common type of childhood cancer and its etiology is largely unknown. Most case-control studies of childhood leukemia have reported elevated risks among children whose parents were occupationally exposed to pesticides or who used pesticides in the home or garden. Investigators at the University of California at Berkeley (UCB) conducted a case-control study of child...

Jul 1st, 2022 - Two large, nutritional intervention trials were conducted in Linxian, China between 1985-1991. These trials tested the effect of multiple vitamins and minerals in the prevention of esophageal cancer in a population with the highest known rate for this disease in the world. Results from the trials showed that Beta-carotene + Vitamin E + selenium reduced total mortality, total cancer mortality, a...

Jul 1st, 2022 - Retinoblastoma is a rare pediatric ocular tumor caused by germline and/or somatic mutations in the tumor suppressor gene RB1. Survivors of retinoblastoma, particularly those with the hereditary form of the disease (germline RB1 mutations) are highly susceptible to developing additional malignancies, which are a major cause of morbidity and mortality. Since 1984, REB has followed a cohort of 213...

Jul 1st, 2022 - The understanding of the biological mechanisms underlying preterm birth is very limited, making prevention of preterm birth difficult. The incidence of preterm birth worldwide varies between 6%-11% in singleton pregnancies, and 64-93% of preterm deliveries occur after the spontaneous onset of labor (preterm labor). The risk factors associated with preterm birth include demographic variables suc...

Jul 1st, 2022 - Preterm labor is a leading cause of perinatal morbidity and mortality. Several investigators have reported that ultrasound evaluation of the cervix can predict the risk of preterm delivery. Three-dimensional ultrasound may provide additional information about how to best counsel parents about the chances of premature birth. This technology has the capability for accurate volume measurements of ...

Jul 1st, 2022 - Diesel exhaust has been classified as a probable carcinogen by the International Agency for Research on Cancer and as a potential carcinogen by the National Institute for Occupational Safety and Health (NIOSH). The carcinogenicity of this pollutant is of concern not only for the one million workers who are exposed occupationally, but also for the general population. Over 30 epidemiologic studie...

Jul 1st, 2022 - A major goal of modern perinatal and neonatal medicine is to reduce the rate of developmental disabilities, especially mental retardation. Cerebral palsy is frequently associated with neurologic abnormalities and mental retardation. Improvements in neonatal intensive care have resulted in improved survival of very low birthweight infants but also in an increased frequency of cerebral palsy. Pre...

Jul 1st, 2022 - Background: Chronic graft-versus-host disease (cGVHD) is the leading cause of non-relapse morbidity and mortality in persons after allogeneic hematopoietic stem cell transplantation (SCT). Bronchiolitis obliterans syndrome (BOS) is a complication of cGVHD associated with a high morbidity and mortality, and treatment options are limited. Neutrophil elastase (NE) is a protease released by neutrop...

Jul 1st, 2022 - Objective: The primary objective is to explore the clinical and biological phenotypes of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). The secondary objective is to explore the pathophysiology of fatigue and post-exertional malaise (PEM). Study population: Up to 206 persons will be enrolled as part of this protocol. Up to 150 persons aged 18-60 will be part of ...

Jul 1st, 2022 - Objective: To assess if there are differences in [18F]florbetaben uptake following the first 120 minutes of its injection (reflecting amyloid-beta or Ab load and/or docked Ab) in subjects during rested wakefulness (RW) after normal sleep compared to wakefulness after 24 hrs of sleep deprivation (SD). Specifically, we hypothesize that during RW after a normal night s sleep there will be less [18...

Jul 1st, 2022 - Human phagocytic cells such as polymorphonuclear leukocytes (neutrophils or PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and antimicrobial peptides released into forming bacterial phagosomes kill most ingested bacteria. However, many bacterial pathogens have devised means to ...

Jul 1st, 2022 - Current diagnosis of the lymphoid malignancies relies upon the morphological appearance of the cancer cells supplemented by a few molecular markers. Within a diagnostic category, the clinical courses and responses of patients to therapy are variable, suggesting that the existing diagnostic categories may harbor more than one disease entity. Recent genomic technologies allow a comprehensive mole...

Jul 1st, 2022 - The aim of this project is to establish a clinical database and a bank of biological materials which will be used to improve the pathophysiologic understanding of the mechanisms underlying various pregnancy diseases. The US-Mexico Reproductive Health Research Development Workshop, sponsored by the NIH, recommended that the setting up of "tissue, blood, and placental banks from human and relevan...

Jul 1st, 2022 - Background -NCI-Frederick scientists performing in vitro studies involving human specimens have a need for a reliable and consistent source of samples which protects the donor from research risks. Objective -The purpose of this protocol is to establish a centralized repository for the collection and distribution of samples (either blood, buccal mucosal cells, semen, urine, or nail clippings) fr...

Jul 1st, 2022 - This project is a continuation of an extensive longitudinal population-based epidemiological investigation of the etiology and determinants of type 2 diabetes (and its complications) and formerly arthritis. The original baseline observations were made on the residents of the Gila Indian Reservation, predominantly Pima Indians, in 1965. We attempt to reexamine the population at two-yearly interv...

Jul 1st, 2022 - In recognition of the emerging social and scientific research related to assessing the complex relationships between self-identified race, ancestral origin and the genetic components of diseases, it is important to study physicians and other health professionals knowledge of human genetic variation and how they interpret and apply race, ethnicity and human genetic variation in their clinical de...

Jul 1st, 2022 - The Division of Cancer Preventionl (DCP, formerly DCPC), under extramural contracts to 10 U.S. clinical centers, is evaluating the effectiveness of screening for prostate, lung, colorectal and ovarian cancer (The PLCO Trial). In 1996 the NCI Executive Committee approved the expansion of the PLCO Trial to collect additional materials and to conduct additional studies. About, 74,000 men and 74,00...