Modern apheresis devices, with increased procedural precision, automation, and monitoring, have been shown to allow for safe delivery of apheresis therapies in young children. Medical advances are increasing demand for apheresis procedures like mononuclear cell collection in infants <10 kg, including stem-cell supported chemotherapy, cell collection for chimeric antigen receptor T cell development, and now ex vivo gene therapies for rare genetic diseases. Nevertheless, safe delivery in small infants involves a range of unique considerations and challenges, beyond just size, and experience will vary between centers.
View Article and Find Full Text PDFWhen screening tests of haemostasis are abnormal, it is important to identify at which point in the coagulation cascade dysfunction may be occurring. This may assist to identify a specific deficiency/dysfunction, the type of bleeding to be anticipated, and replacement therapy if required. Unmasking of an inherited coagulopathy or the development of an acquired coagulopathy may occur in the setting of a second (febrile) illness.
View Article and Find Full Text PDFReceptor-interference (Receptor-i) is a novel technology used to identify bioactive peptides as agonists or antagonists against a specific receptor, primarily targeting G-protein-coupled receptors (GPCRs). Using Receptor-i methodology, we targeted the pheromone biosynthesis activating neuropeptide receptor (PBAN-R) of the red imported fire ant (). Based on previous studies, we selected four bioactive peptides cyclized with two cysteines: CVKLGSHFC, CIQQGSHFC, CERVGSHFC, and CMARYMSAC, and we conducted small-scale feeding bioassays, measuring fire ant worker mortality.
View Article and Find Full Text PDFAs the human population and demand for food grow, the ocean will be called on to provide increasing amounts of seafood. Although fisheries reforms and advances in offshore aquaculture (hereafter 'mariculture') could increase production, the true future of seafood depends on human responses to climate change. Here we investigated whether coordinated reforms in fisheries and mariculture could increase seafood production per capita under climate change.
View Article and Find Full Text PDFSocial insect queens have evolved mechanisms to prevent competition from their sexual daughters. For Solenopsis invicta, the fire ant, queens have evolved a primer pheromone that retards reproductive development in their winged reproductive daughters. If these daughters are removed from the influence of the queen, it takes about a week to start reproductive development; however, it starts almost immediately after mating.
View Article and Find Full Text PDFGlobal food demand is rising, and serious questions remain about whether supply can increase sustainably. Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services. As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050.
View Article and Find Full Text PDFBackground: Peripheral artery disease (PAD) is caused by atherosclerotic occlusions in the legs. It affects approximately 8-12 million people in the United States alone, one-third of whom suffer from intermittent claudication (IC), defined as ischemic leg pain that occurs with walking and improves with rest. Patients with IC suffer a markedly impaired quality of life and a high perception of disability.
View Article and Find Full Text PDFLocal recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial.
View Article and Find Full Text PDFThe Food and Drug Administration Amendments Act of 2007 (FDAAA 2007, US Public Law 110-98) mandated registration and reporting of results for applicable clinical trials. Meeting these registration and results reporting requirements has proven to be a challenge for the academic research community. Duke Medicine has made compliance with registration and results reporting a high priority.
View Article and Find Full Text PDFBackground: Infertility patients are increasingly using complementary and alternative medicine (CAM) to supplement or replace conventional fertility treatments. The objective of this study was to determine the roles of CAM practitioners in the support and treatment of infertility.
Methods: Ten semi-structured interviews were conducted in Ottawa, Canada in 2011 with CAM practitioners who specialized in naturopathy, acupuncture, traditional Chinese medicine, hypnotherapy and integrated medicine.
Objective: The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers.
Background: A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role.
Methods: The participants who developed the recommendations were representatives of institutions with IND/IDE support programs.
Background: Medical school is a challenging environment that requires students to deal effectively with stress borne out of the medical education environment, as well as their personal lives. Previous research has not systemically distinguished between academic and personal sources of stress, and in particular has not explored the independent contribution that academic stressors make to medical student depression.
Purposes: This study aimed to investigate whether academic stressors make a unique contribution to the level of depressive symptoms in medical students, over and above the contribution made by personal stressors alone.
Purpose: This study highlights Warning Letter (WL) findings issued to sponsor-investigators (S-Is) by the Food and Drug Administration (FDA).
Methods: The online index of WLs issued from October 1, 2007 through September 30, 2012 was reviewed [1]. Through a manual screening process, letters were evaluated if specifically issued to 'clinical investigators', 'sponsors' or 'sponsor-investigators'.
J Immigr Minor Health
February 2014
Although recent immigrants to Canada are healthier than Canadian born (i.e., the Healthy Immigrant Effect), they experience a deterioration in their health status which is partly due to transitions in dietary habits.
View Article and Find Full Text PDFQuinolone antibacterial drugs such as nalidixic acid target DNA gyrase in Escherichia coli. These inhibitors bind to and stabilize a normally transient covalent protein-DNA intermediate in the gyrase reaction cycle, referred to as the cleavage complex. Stabilization of the cleavage complex is necessary but not sufficient for cell killing--cytotoxicity apparently results from the conversion of cleavage complexes into overt DNA breaks by an as-yet-unknown mechanism(s).
View Article and Find Full Text PDFExperimental batch and miscible-flow cultures were studied in order to determine the mechanistic pathways of microbial Fe(III) respiration in ferruginous smectite clay, NAu-1. The primary purpose was to resolve if alteration of smectite and release of Fe precedes microbial respiration. Alteration of NAu-1, represented by the morphological and mineralogical changes, occurred regardless of the extent of microbial Fe(III) reduction in all of our experimental systems, including those that contained heat-killed bacteria and those in which O, rather than Fe(III), was the primary terminal electron acceptor.
View Article and Find Full Text PDFNalidixic acid, the prototype antibacterial quinolone, induces the SOS response by a mechanism that requires the RecBCD nuclease/helicase. A key step inferred for this induction pathway is the conversion of a drug-induced gyrase cleavage complex into a DNA break that can be processed by RecBC. We tried to clarify the nature of this step by searching for additional gene products that are specifically necessary for SOS induction following nalidixic acid treatment.
View Article and Find Full Text PDFThe bacterial SOS regulon is strongly induced in response to DNA damage from exogenous agents such as UV radiation and nalidixic acid. However, certain mutants with defects in DNA replication, recombination, or repair exhibit a partially constitutive SOS response. These mutants presumably suffer frequent replication fork failure, or perhaps they have difficulty rescuing forks that failed due to endogenous sources of DNA damage.
View Article and Find Full Text PDFBacteriophage T4 provides a useful model system for dissecting the mechanism of action of antitumor agents that target type II DNA topoisomerases. Many of these inhibitors act by trapping the cleavage complex, a covalent complex of enzyme and broken DNA. Previous analysis showed that a drug-resistant T4 mutant harbored two amino acid substitutions (S79F, G269V) in topoisomerase subunit gp52.
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