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The objective of this study is to evaluate the safety and performance of the AmM APTITUDE Bioresorbable Drug-Eluting Coronary Scaffold for use in the treatment of single, de novo, stenotic native coronary artery lesions in patients undergoing elective percutaneous coronary intervention. The scaffold is a single-use device comprised of a balloon-expandable, intracoronary drug coated scaffold pre-mounted on a rapid-exchange delivery catheter. The scaffold is made of Poly-L-Lactide (PLLA) and is coated with a polymer-antiproliferative drug (sirolimus) matrix. The scaffold provides mechanical support similar to a metallic stent to the vessel while it is healing, and then gradually breaks down over time leaving no permanent implant in the treated vessel. Compared to prior versions of the scaffold, the new device has a thinner strut design (a wall thickness of 120 µm rather than 150 µm), but is otherwise identical. The study design is a prospective, non-randomized, multi-center, non-inferiority trial. It will enroll a maximum of 60 patients from up to 12 investigational centers in Colombia and the European Union. Eligible patients who are at least 18 years of age diagnosed with symptomatic ischemic disease due to a discrete, single, de novo, stenotic lesion in native coronary artery will be asked to participate in this study. After treatment with the investigational device, subjects will be followed for five years. Safety of the device will be evaluated using the incidence of target vessel failure during the follow-up period. Performance (efficacy) will be assessed using the in-scaffold late lumen loss measured by quantitative coronary angiography at nine months. The purpose of this study is to evaluate the safety and performance of a new version of a coronary artery stent for treating blockages in the arteries supplying blood to the heart muscle. The Amaranth Medical APTITUDE scaffold releases a drug (sirolimus) to reduce the likelihood of the treated blood vessel developing a new blockage. In addition, the scaffold dissolves away over time, leaving no permanent implant after the blood vessel has healed.

Approximately, 50 patients in each groups undergoing orthopedic surgery of upper extremities will be randomized to be one of the three groups to receive supraclavicular nerve block with group 1: ropivacaine alone; group 2: ropivacaine and dexamethasone; group 3: ropivacaine and clonidine or group 4: ropivacaine and dexamethasone and clonidine combination. Patients will be identified at the day surgery unit at Parkland hospital before the procedure and will be approached by their physician, the primary investigator, or research personnel for the consent for the study. If the patient chooses and consents fully to participate, he or she will be randomly assigned to receive one of the previously described local anesthetics for supraclavicular nerve block. The following clinical outcome will be assessed for up to 24 hr: Duration of the block, onset of the block, nausea, the number of vomiting, and complications of peripheral nerve block and used medications will be recorded. Pain at rest and movement will be evaluated by using a linear 10-cm visual analog scale (VAS; 0=no pain, 10= worst imaginable pain) immediately before the block, 5, 10, 15 minutes and 6 hr. after the block and postoperatively immediately at PACU, discharge from the Day surgery Unit, and 24 hr. later at home via phone call visit. Sensory and motor block in the related nerve dermatomes (via pinprick test) will be assessed. Patient will be instructed to document at what time did hand motion (finger movement) return and what time normal sensation (hot/cold) return. Specific time for both events will be asked to patient at phone call visit 24 hr later. Overall patient satisfaction will be evaluated at the discharge from the day surgery and 24 hr after the block via phone visit. At any point in which the patient is not experiencing pain relief after having received the injection, they will be removed from the study and other anesthetic techniques will be applied to resolve their pain along with pharmacological management of their pain. Rescue antiemetic, which is standard of care, will be given to any patient who complains of nausea or vomiting. The aim of this randomized, observer-blinded clinical trial is to evaluate the anesthetic and analgesic efficacy of adding dexamethasone and clonidine to ropivacaine in supraclavicular nerve block. The investigators hypothesized that addition of dexamethasone and clonidine to ropivacaine would prolong the duration of analgesia in supraclavicular nerve block compared with ropivacaine alone.

The specific aims for this project are to enroll up to 10,000 subjects who will have their genomes surveyed using the Navigenics™ Health Compass technology. The Navigenics Health Compass helps you understand what your genetic variants have to say about the future of your health, and gives you action steps to take control of your health today. In addition, the investigators will assess how the Navigenics Health Compass, results affect lifestyle decisions. The phenotyping information that can be analyzed with the resulting Navigenics genotype information will assist in identifying genetic variations associated with other traits and diseases. The uses of molecular markers such as cholesterol and glucose levels to assess disease risk are well established in clinical medicine today. Although these tools are useful in screening for subclinical disease, their predictive value is limited. Until recently, these molecular markers were the best risk assessment and screening tools in existence. Since the completion of the Human Genome Project, the era of personalized medicine, which exploits knowledge of the genes an individual carries that may predispose him/her to disease, has come to the forefront of research. The Navigenics Health Compass technology assesses risk for about over 20 common diseases and provides subjects with more accurate assessments of their individual predictive risk for developing these conditions than traditional biomarkers such as cholesterol and glucose levels. This may positively influence changes in lifestyle, as well as decisions to seek further medical evaluation associated with preventive strategies.

The survival of subjects with unresectable hepatocellular carcinoma (HCC) receiving transarterial chemoembolization is improved with addition of axitinib.

Determination of allergenicity of cat dander samples obtained before and after vaccinating the cat

Subjects: Thirty overweight hyperlipidemic subjects who wish to lose weight. Design: - Protocol (Metabolic Study): will be randomized to either the Eco-Atkins diet (15 subjects) or NCEP diet (15 subjects). The diets will be provided for the one month period with the aim of inducing the same weight loss (5 kg) as seen in the first month of the published reports on the Atkins diet. The diets will provide about 60% of estimated energy requirements. Subjects will be provided with their diets at weekly intervals by courier and intakes adapted to ensure that they achieve their target weight loss goal. Fasting weight will be taken at weekly intervals together with blood pressure and blood for lipids, glucose and insulin assessment. - Protocol (Ad Libitum Study): After completing the metabolic phase of the study, the thirty subjects will be asked to continue with the diet to which they were randomized for a further 6-month period. During this ad libitum trial, study foods will not be provided. This longer less tightly controlled study will establish the value of this diet in "real life" situations. This will be required to support our shorter term, well-controlled more detailed metabolic study. Fasting weight will be taken at monthly intervals together with blood pressure and blood for lipids, glucose and insulin assessment. Study Details: Participants will come after a 12h overnight fast to the Risk Factor Modification Centre at St. Michael's Hospital or the Department of Nutritional Sciences, University of Toronto immediately prior to commencement of each treatment phase and at weekly intervals during the metabolic study and monthly during the ad libitum study. Prior to the start of the study, participants will be instructed on details of the study diet protocol. They will also be asked to maintain a constant level of physical activity throughout the course of the study. At all visits, body weight (in kg) will be obtained in indoor clothing, without shoes, and blood pressure will be taken twice in the dominant arm after participants have been seated for at least 20 minutes. Height (in cm) will be recorded at the first visit. Body composition measurements will be measured using bioelectric impedance at baseline and week 4 of the metabolic phase, and months 3 and 6 of the ad libitum phase. Throughout the study period, participants will maintain the diet prescribed on their initial visit. At each visit, participants will provide a fasting blood sample and seven-day food records will be collected. During the last week of the metabolic and ad libitum study, 24h fecal and urine collections will be completed. Exchange of the butter, eggs, cheese and meat in the Atkins diet for soy protein foods, other vegetable proteins including gluten and vegetable fats, nuts, avocado, olive and canola oil will result in dramatic rather than modest reductions in blood lipids with weight loss. In effect this will represent an exchange of saturated fat and animal protein for healthy monounsaturated and polyunsaturated fats and vegetable proteins with significant effects on blood lipids while still encouraging weight loss.

Our previous studies have demonstrated sex differences in both the reinforcing properties of (Temple JL, Briatico LN, Clark EN, Dewey AM, 2009) and physiological responses to (Temple JL, Dewey AM, Briatico LN, 2010) caffeine. This is consistent with the literature on other types of drugs showing that men and women often differ in both drug self administration (Lynch WJ,2008 ) and drug sensitivity (Temple, JL, et al, 2008). These differences have been attributed, at least in part, to differences in gonadal hormones (Lynch WJ, 2008) ,Dreher JC et al, 2007). Our laboratory conducted a study investigating subjective effects of caffeine in post-pubertal adolescents and found that boys reported greater drug effects and liking of drug effects than did females (Temple JL, Dewey AM, Briatico LN, 2010, Temple JL, Ziegler AM,2011). In addition, the differences in feeling of the drug effects were related to salivary estradiol levels in females, but not in males, suggesting that steroid hormones can mediate the subjective effects of caffeine. When taken together, these data suggest that there are gender differences in acute and chronic effects of caffeine and that these differences may be mediated by differences in circulating steroid hormones. Previous studies have shown that subjective responses to caffeine vary across the menstrual cycle (Terner JM, de Wit H, 2006), with the greatest subjective effects occurring during the follicular phase, when estradiol levels begin to rise and peak just prior to the ovulatory LH surge. To date, no well-controlled studies have been conducted in humans examining the relationship between steroid hormones and caffeine effects on cognition, which the investigators will address in this study. Caffeine use is on the rise in America, and one of the most popular sources is soda. Among youth ages 8-16, caffeine consumption has increased by over 70% in the past 30 years. Few studies have examined the role of hormones in caffeine consumption within this age group. The purpose of the current experiment was to determine the effect of caffeine on children 8 and 9 compared to those 15 and 16 years of age. The investigators were looking at the effect of puberty on the consumption of caffeine as well as the effect that the caffeine has on the body (for example: heart rate, blood pressure) and cognitive function.

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a very rare and uniformly fatal genetic condition that affects the microvasculature. Symptoms begin in adulthood (usually in the 40s) and include loss of vision, mini-strokes, and dementia. RVCL includes three conditions which were previously thought to be distinct: hereditary endotheliopathy, retinopathy, nephropathy, and stroke (HERNS); cerebroretinal vasculopathy (CRV); and hereditary vascular retinopathy (HVR). RVCL is inherited in an autosomal dominant manner and is caused by carboxyl (C)-terminal heterozygous frameshift (fs) mutations in TREX1 (Three Prime Repair Exonuclease 1). There is no treatment for RVCL, only symptomatic management. TREX1 is an endoplasmic reticulum (ER)-associated (i.e., intracellular) enzyme that, in addition to its DNA repair activities, may regulate sugar metabolism in the ER. TREX1 mutations have also been associated with several autoimmune and autoinflammatory diseases. In RVCL, fs mutations of TREX1 result in C-terminal truncation and this dysregulates the oligosaccharyltransferase (OST) complex leading to free glycan release from dolichol carriers. In mouse models and in patient-derived cells, inhibiting OST with aclarubicin may correct glycan and immune defects associated with fs mutations of TREX1 (Hasan, M. et al., Immunity 43: 1-12, 2015). Aclarubicin (aka aclacinomycin, aclacinomycin-A) is an anthracycline antibiotic isolated from Streptomyces galilaeus cultures. Aclarubicin has been shown to have a broad spectrum of anti-tumor activity. Aclarubicin was utilized for treatment of various cancers in Phase 1 and 2 studies in the United States of American (USA) in the 1980's and 1990's. While no longer clinically employed in the USA, it is commonly used in China and Japan, often as part of a combination drug therapy program for certain malignancies. Aclarubicin is typically administered over 3-5 consecutive days, however, alternative schedules such as weekly or monthly have been evaluated. In solid tumors, the maximum tolerated dose (MTD) of 4-day dosing was 30 mg/m2/day; marrow suppression was dose limiting, otherwise the regimen was well tolerated. Additionally, a Phase II study in acute myeloblastic leukemia was conducted using 100mg/m2 per day for three days and repeated at days 14-16 if marrow hypoplasia was not produced. Toxic effects of this regimen included severe neutropenia, nasea/vomiting, and diarrhea. No changes were noted in left ventricular ejection fraction or no cardiac symptoms developed. RVCL is caused by fs mutations in the C-terminus of TREX1 resulting in low-grade free glycan release, immune activation, and possibly autoantibody production due in part to dysregulation of the OST complex. Inhibiting OST with aclarubicin corrects these glycan and immune defects in mouse models and in patient-derived cells. Thus, inhibiting OST with aclarubicin might be a therapeutic option for patients with RVCL. Given the poor prognosis of RVCL, the lack of treatment options, and the pre-clinical data on OST inhibition by aclarubicin in mice, there is strong rationale for conducting a clinical trial of aclarubicin in patients with RVCL. In this pilot study, aclarubicin will be administered initially at <10% of the single-agent maximum tolerated dose (MTD) in oncology studies. Assessments will be made every six months as to objectives of the study. Patients that do not have clear objective response may be dose escalated by 1 dose level with permission of the principal investigator permitting the patient has not previously experienced any toxicities requiring dose modifications. A patient who has clear objective progression at any time may also have their dose escalated as long as they have completed 1 full cycle at their current dose level. Maximum dose level will be 24 mg/m2/day. The aim of aclarubicin administration in RVCL is not to induce apoptosis, as in oncology studies, but rather to modulate intracellular functions and, thus, a reduced dose will be utilized. The goal of the investigator is to utilize Aclarubicin to treat patients with Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL), a rare and devastating genetic disease with no available specific treatment. RVCL results from a mutation in the tail end of the TREX1 (Three Prime Repair Exonuclease 1) gene, a major deoxyribonucleic acid (DNA) repair enzyme. The RVCL-specific mutations cause expression of a truncated and mislocalized protein. RVCL is an inherited disorder whose symptoms begin at middle age and initially predominantly affects the eye and brain. Because it is an 'autosomal dominant' disease, it strikes both males and females equally. A person with RVCL has a 50-50 chance of transmitting the gene to each child. The investigator's published studies demonstrated in a mouse model for RVCL and in vitro studies with patients' cells that defects were corrected by use of Aclarubicin, an anthracycline antibiotic often used to treat cancer. Thus, there is a strong rationale for conducting a clinical trial of aclarubicin in patients with RVCL. The dosage to be initially administered to RVCL patients initially will be < 10% of that typically used in cancer therapeutics and will be given monthly on four consecutive days for six months. Patients will undergo assessments every six months to determine disease response. Patients that do not have clear objective response may be dose escalated by 1 dose level with permission of the principal investigator permitting the patient has not previously experienced any toxicities requiring dose modifications. We will evaluate the safety and clinical efficacy of Aclarubicin for the treatment of RVCL and evaluate its effects on cellular function. This work will generate the first clinical research data on the investigational product's utility in treating RVCL.

This is an open-labeled dose escalating trial in which a total of 32 subjects (minimum of 24 allowable) will receive one of four intranasal Invaplex 50 vaccine doses according to the following chart: Test articles/dose Group / N* / Invaplex 50 A / 8 / 10 micrograms B / 8 / 50 micrograms C / 8 / 240 micrograms D / 8 / 480 micrograms *minimum of 6 volunteers/group An interval no less than 7 days following the third (and final) dose (total of 35 days between initial dose at the lower dose level and the next initial dose at the next higher dose level) will separate volunteer groups receiving different doses. All volunteers will receive three immunizations. The first dosing time point is Day 0, the second is Day 14 (+- one day), and the third is Day 28 (+- 2 days). Blood and stool specimens will be collected at intervals to examine systemic and mucosal vaccine antigen-specific immune responses. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccination dose. The vaccine is given as a nose spray. Volunteers will receive a 3-dose vaccination with doses spaced two weeks apart. Volunteers will be assigned to a vaccination group based on their order of enrollment with consideration of their availability to complete the necessary vaccinations and follow-up visits.

Sarcoidosis is a systemic granulomatous disease of unknown cause, most commonly affecting the lungs, which tends to afflict young adults in the prime of their lives. Recent data indicating that sarcoidosis mortality rates are rising in the U.S. (1) and Europe (2) highlight the inadequacy of current therapies. As noted in a recent NIH-sponsored sarcoidosis workshop, the lack of relevant animal, computer or in vitro models represents a bottleneck for progress towards understanding disease mechanisms and developing highly effective sarcoidosis treatments (3). The lack of useful disease models likely contributes to the current lack (zero) of investigator-initiated (RO1) projects supporting sarcoidosis research. The long-term goal of this proposal is to develop a novel human sarcoidosis research model to fill the current void in the field, thereby expediting exploration of basic disease mechanisms and pre-clinical testing of novel therapies. The objective of this application, which is the first step towards achieving the long-term goal, is to develop a novel in vitro human granuloma model to represent abnormal granuloma formation in the context of sarcoidosis. In this regard, a growing body of evidence indicates that mycobacterial antigens are commonly harbored in sarcoidosis tissues, to which these patients are sensitized (4, 5). Our central hypothesis is that the pathological mechanisms of sarcoidosis can be modeled in vitro, as represented by abnormal granuloma formation in response to mycobacterial and other ubiquitous environmental antigens. The feasibility of our proposed model is supported by preliminary studies showing that subjects sensitized to Mycobacterium tuberculosis antigens (latent TB tuberculosis with a positive TB skin test) form well-organized granulomas readily in response to challenge with TB antigens, compared to healthy controls. This project is highly innovative and we feel has an excellent likelihood of leading to a critical breakthrough in the field of sarcoidosis research. There is currently no experimental model that accurately represents sarcoidosis. The lack of a useful research model significantly slows progress towards developing new treatments for sarcoidosis. The investigators plan to develop a new model for sarcoidosis research and will test the model to see if it helps us understand how sarcoidosis develops and if it is useful for testing new treatments.