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Latest Paper:
Quality and Safety Education for Nurses (QSEN) faculty outlined 6 competency domains: patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics. In this study, 18 subject matter experts participated in a web-based modified Delphi survey between October 2008 and February 2009 to determine whether there was consensus on the developmental progression of knowledge, skill, and attitude elements within the QSEN competencies. Support for creation of curricular threads to facilitate student progressive achievement of the QSEN competencies was validated. Competency development related to the individual patient was emphasized early in the curriculum, whereas teams and systems were emphasized later. Complex concepts such as teamwork and collaboration, evidence-based practice, quality improvement, and informatics were emphasized in advanced courses. Experts outlined a developmental approach in curriculum design, which would potentially encourage practice, reinforcement of learning, and recognition of context of care.
Svetlana Marukian,
Christopher T Jones,
Linda Andrus,
Matthew J Evans,
Kimberly D Ritola,
Edgar D Charles,
Charles M Rice,
Lynn B Dustin
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY.
Hepatitis C virus (HCV) replicates primarily in the liver, but HCV RNA has been observed in association with other tissues and cells including B and T lymphocytes, monocytes, and dendritic cells. We have taken advantage of a recently described, robust system that fully recapitulates HCV entry, replication and virus production in vitro to re-examine the issue of HCV infection of blood cell subsets. The HCV replicase inhibitor 2'C-methyl adenosine was used to distinguish HCV RNA replication from RNA persistence. Whereas cell culture-grown HCV replicated in Huh-7.5 hepatoma cells, no HCV replication was detected in B or T lymphocytes, monocytes, macrophages, or dendritic cells from healthy donors. No blood cell subset tested expressed significant levels of Claudin-1, a tight junction protein needed for HCV infection of Huh-7.5 cells. A B cell line expressing high levels of Claudin-1, CD81, and scavenger receptor BI remained resistant to HCV pseudoparticle infection. We bypassed the block in HCV entry by transfecting HCV RNA into blood cell subsets. Transfected RNA was not detectably translated and induced high levels of interferon-alpha. Supernatants from HCV RNA-transfected macrophages inhibited HCV replication in Huh-7.5 cells. Conclusion: We conclude that multiple blocks prevent blood cells from supporting HCV infection.(HEPATOLOGY 2008.).
Kongkrit Chaiyasate,
Michael Jacobs,
Steven E Brooks,
Gelen Del Rosario,
Lee Andrus,
William Kestenberg,
Vijay Mittal
BACKGROUND: Roux Stasis Syndrome is a well-known complication after Roux-en-Y reconstruction. It has been hypothesized that reconstruction with an uncut Roux limb and jejunal pouch after total gastrectomy would preserve unidirectional intestinal myoelectrical activity, improve postoperative weight gain and nutritional parameters, and diminish Roux Stasis Syndrome in canines. METHODS: A total gastrectomy was performed, and 2 methods were used for reconstruction: Roux-en-Y esophagojejunostomy (RY) was performed on 5 canines (control), and the uncut Roux-en-Y with a jejunal pouch (URYJP) was performed on 5 other canines (experimental). The canines were monitored for 10 weeks postoperatively. Serial weight and nutritional parameters were measured. Emptying profiles and motility studies were performed in the fasting and postprandial states. RESULTS: Ten weeks after operation, the URYJP group had significantly improved nutritional parameters, including weight, total protein, albumin, hemoglobin, serum total iron binding capacity, and serum IgA, IgG, and IgM. The emptying times for both groups were similar, with an increase of disordered propagation of the jejunal pacesetter potential in the RY group. The aboral propagation occurred more frequently in the URYJP group during fasting and after feeding (98%+/- 1% vs 39%+/- 16%; P =.02, and 99%+/- 1% vs 43%+/- 18%; P =.03). The sites of luminal occlusions were intact in the URYJP group at 10 weeks. CONCLUSIONS: The combination of jejunal pouch and uncut Roux limb improved overall nutritional parameters when compared with the traditional Roux-en-Y, while preserving aboral propagation of jejunal pacesetter potentials.
Alfred M Prince,
Betsy Brotman,
Dong-Hun Lee,
Wolfram Pfahler,
Nancy Tricoche,
Linda Andrus,
Mohamed T Shata
Laboratory of Virology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA; Vilab II, Liberian Institute for Biomedical Research, Robertsfield, Liberia. aprince@nybloodcenter.org.
An open question for hepatitis C virus (HCV) vaccine development is whether the various genotypes of this virus protect against the development of chronic infection after heterologous infection with different genotypes. We approached this question by challenging chimpanzees that had recovered from HCV genotype 1a or 1b infection with 6 heterologous genotypes as well as with a homologous genotype (for chimpanzees originally infected with genotype 1a). All 9 chimpanzees rechallenged with a homologous genotype developed self-limited infections. Of 11 chimpanzees challenged with 100 chimpanzee infectious doses of heterologous genotypes, 6 developed self-limited infections, with peak viral loads in acute-phase serum that were ~5-fold lower than those seen during primary infections. One chimpanzee (which had recovered from genotype 1b infection and was rechallenged with genotype 6a) did not develop viremia but did show an anamnestic cell-mediated immune response after rechallenge. Four of the 11 chimpanzees rechallenged with heterologous genotypes developed chronic infections with the genotypes used for rechallenge. These findings suggest that a universally protective HCV vaccine may need to incorporate epitopes from multiple genotypes.
Dong-Hun Lee,
John Mathew,
Wolfram Pfahler,
Dongling Ma,
Jay Valinsky,
Alfred M Prince,
Linda Andrus
We have developed an economical, high-throughput nucleic acid amplification test (NAT) for blood-borne viruses, suitable for use in the screening of plasma samples from individual blood donors. This assay system includes a semiautomated procedure, using 96-well glass fiber plates for the extraction of viral nucleic acids from plasma and "universal beacon" technology which permits the detection of all genotypes of highly variable viruses (e.g., human immunodeficiency virus and hepatitis C virus). In this detection system, two fluorescent- detection technologies were employed successfully in a single tube: molecular beacon for West Nile virus (WNV) detection using a 6-carboxyfluorescein fluorophore and TaqMan for internal control detection using a VIC fluorophore. To establish proof of concept, we focused on the development of a robust individual donor NAT for WNV. The assay showed no reactivity to 15 other viruses tested or to 420 blood donor samples from the WNV pre-epidemic season. No cross-contamination was observed on an alternating positive-/negative-well test. The sensitivity (limit of detection, 95%) of the assay for WNV is between 3.79 and 16.3 RNA copies/ml, depending on which material was used as a standard. The assay detected all positive blood donation samples identified by the Roche WNV NAT. The assay can be performed qualitatively for screening and quantitatively for confirmation.
Mesh-terms: Blood Donors; Fluoresceins; Fluorescent Dyes; Humans; Nucleic Acid Amplification Techniques :: methods; RNA, Viral :: blood; RNA, Viral :: isolation & purification; Reproducibility of Results; Sensitivity and Specificity; Taq Polymerase; West Nile Fever :: diagnosis; West Nile Fever :: virology; West Nile virus :: genetics; West Nile virus :: isolation & purification;
Institute for Craniofacial and Reconstructive Surgery, Province Hospital, Southfield, MI, USA. eero.waris@helsinki.fi
A self-reinforced bioabsorbable poly-L-lactide/polyglycolide (SR-PLGA) 80/20 screw 2.0 mm in diameter was implanted transphyseally across the distal growth plate of the right femur in 24 immature rabbits. Radiologic evaluation revealed a mean shortening of 3.1 mm at 3 weeks, 11.1 mm at 6 weeks, 9.3 mm at 24 weeks, 9.0 mm at 48 weeks, and 12.6 mm at 72 weeks compared with the intact contralateral femur. In 13 control rabbits, drilling without screw placement did not cause any statistically significant femoral shortening. Therefore, the transphyseal SR-PLGA 80/20 screw caused growth retardation for 6 weeks postoperatively, after which the normal growth tendency was recovered until the growth plate was closed. The duration of temporary growth retardation correlated with that of strength retention of the SR-PLGA 80/20 copolymer. These findings suggest that SR-PLGA 80/20 screws can be applied in transphyseal bone fixation. The use of bioabsorbable screws for temporary epiphysiodesis seems attractive but requires further study.
Andrea Moreira-Gonzalez,
Catherine Lobocki,
Khaled Barakat,
Lee Andrus,
Melinda Bradford,
Milessa Gilsdorf,
Ian T Jackson
Institute for Craniofacial and Reconstructive Surgery, 16001 West Nine Mile Road, Southfield, MI 48075, USA.
Biomaterial research and tissue engineering have guided new developments in bone replacement. In this study, the osteoconductive and osteoinductive properties of 45S5 Bioglass (Novabone-C/M, Porex Surg., Newnan, GA), granules as a bone replacement material for large calvarial defects were evaluated. Rabbit periosteal cells were expanded in culture and used in vivo. Alkaline-phosphatase assay, collagen type I, and calcium expression were applied to confirm osteoblast phenotype. In the in vivo phase, a 15-mm diameter critical size calvarial defect was created in rabbits (n = 14). The defect was reconstructed according to four treatment groups: autogenous bone (n = 2), Bioglass alone (n = 2), Bioglass + bone (n = 5), Bioglass + periosteal cells (n = 5). The animals were killed 12 weeks after surgery, and the samples were analyzed. Periosteal cells grew successfully in vitro. Because of their fast proliferation and potential to differentiate into osteoblasts, they were an excellent source of cells for bone tissue engineering. The best ossification was seen when autogenous bone was used (79.4% ossified), whereas only 8.2% of the defect in the Bioglass group showed ossification. Addition of bone or cells to the Bioglass increased the area of ossification to 42.7% and 30.2%, respectively. Defects replaced with Bioglass showed varying degrees of inflammatory reaction because of the intense cell-mediated biodegradation process. Based on these findings, the use of Bioglass granules to repair large craniofacial defects cannot be advised.
Mesh-terms: Alkaline Phosphatase :: analysis; Animals; Biodegradation; Bone Diseases :: surgery; Bone Substitutes :: therapeutic use; Bone Transplantation; Calcium :: analysis; Collagen Type I :: analysis; Female; Glass; Osteoblasts :: pathology; Osteoblasts :: transplantation; Osteogenesis :: physiology; Parietal Bone :: surgery; Periosteum :: pathology; Phenotype; Rabbits; Reconstructive Surgical Procedures; Time Factors; Tissue Engineering;
Andrew H Jackson,
Daniel A Degner,
Ian T Jackson,
Takeshi Miyawaki,
Boris Silverberg,
Melinda Bradford,
Lee Andrus
Michigan Veterinary Specialists, Southfield, MI 48076, USA.
OBJECTIVE: To develop and assess the survival of a microvascular cutaneous free flap based on the ventral branch of the deep circumflex iliac (DCI) artery and vein in cats. STUDY DESIGN: Experimental study. ANIMALS: Phase 1: 6 feline cadavers; Phase 2: 2 adult cats; Phase 3: 10 adult cats. METHODS: Phase 1: Selective angiographic study of the deep circumflex iliac artery was completed in 6 feline cadavers. After injection of the DCI artery with barium, high-detail radiographs were made of skin flaps harvested from the lateral flank and thigh region. The extent of the cutaneous angiosome was mapped with regard to the underlying anatomical landmarks. Phase 2: An island flap based on anatomic boundaries of the DCI angiosome derived from phase 1 of the study was elevated in 2 cats. Flaps were observed for 3 weeks for survival. Phase 3: Free skin flaps based on the DCI vessels were harvested in 10 cats and transferred to the dorsal interscapular region. Flaps were evaluated for 2 weeks for survival. Tissue samples were collected for histopathology, and angiograms of the flaps were completed. RESULTS: Phase 1: Angiograms revealed a large primary cutaneous angiosome of the DCI artery located over the lateral femoral region, which extended from the iliac crest to the level of the patella. Phase 2: All island flaps survived for 3 weeks. Phase 3: Six free flaps survived for 2 weeks, and 4 flaps failed completely. Failure of 1 flap occurred because of avulsion of the venous and arterial anastomosis postoperatively. Another cat had intraoperative hemorrhage, which resulted in anemia and hypovolemia and likely caused the flap to fail. The other 2 flaps that failed had poor perfusion intraoperatively and had the longest ischemia times. CONCLUSIONS: The cutaneous DCI free flap in cats may be clinically useful in reconstruction of large cutaneous wounds. The length of ischemia time for successful cutaneous free flap transfer in the cat may be shorter than in other species. CLINICAL RELEVANCE: Large wounds created by trauma or oncologic ablative surgery in cats could be reconstructed with cutaneous microvascular free flap. Additional studies assessing the critical ischemia time of cutaneous flaps in cats and evaluating the use of this flap clinically are needed.
New York Blood Center, Lindsley F. Kimball Research Institute, Virology Laboratory, New York 10021, USA. mohamed.shata@NYBC.org
The immune response to hepatitis C virus (HCV) is believed to be critical in determining the outcome of the disease. In this study we have analysed epitope recognition, cytokine profile, and anti-HCV antibody responses in chronically HCV-infected and recovered chimpanzees. Quantitative measurement of anti-HCV antibody in HCV-infected chimpanzees revealed that the response in HCV- recovered chimpanzees peaked within 4-20 weeks. In contrast, the anti-HCV antibody responses in chronically HCV infected chimpanzees did not peak until 100-200 weeks after infection, and decreased gradually thereafter. T cell proliferation assays measuring responses to pooled HCV proteins revealed significant increases in the 3H-uptake during the early stages of infection in recovered chimpanzees in comparison to the chronically infected ones. Class I-restricted epitopes of the core, and NS3 proteins of HCV were analysed using 9-10 mer overlapping peptides covering the core and NS3 proteins, and IFN-gamma ELISPOT technique. Our data indicated early and broad class-I restricted core, and NS3 protein epitope recognitions in HCV-recovered chimpanzees but not in chimpanzees that had been chronically infected. Additionally, dominant epitopes recognized early in infection (8 weeks) were no longer recognized later in infection (followed up to 64 weeks). Cytokines profiling revealed a 50-fold increase in TNF-alpha secretion in the supernatant of core-specific CD8 memory cells of the chronically infected chimpanzees in comparison to the recovered ones. In summary, multiple parameters correlate with HCV recovery in chimpanzees.
Mesh-terms: Animals; CD4-Positive T-Lymphocytes :: immunology; CD8-Positive T-Lymphocytes :: immunology; Disease Models, Animal; Epitope Mapping; Epitopes, T-Lymphocyte; Female; Hepacivirus :: immunology; Hepatitis C :: immunology; Hepatitis C :: virology; Hepatitis C Antibodies :: blood; Hepatitis C, Chronic :: immunology; Hepatitis C, Chronic :: virology; Histocompatibility Antigens Class I :: metabolism; Human; Male; Pan troglodytes; Peptides :: immunology; Support, U.S. Gov't, P.H.S. ; Tumor Necrosis Factor :: metabolism; Viral Core Proteins :: chemistry; Viral Core Proteins :: immunology; Viral Nonstructural Proteins :: immunology;
