The heat stable antigen (CD24) is not required for the generation of CD4+ effector and memory T cells by dendritic cells in vivo

Previous work has established that CD24 is a costimulatory molecule for T-cell clonal expansion. Studies using CD24 -/- mice demonstrated that CD24 plays a critical role in the CD28-independent immune response against virus and soluble antigens. The role of CD24 on dendritic cells (DCs) has not been reported. Here, we compare the CD24(+/+) and CD24(-/-) DCs in the induction of initial clonal expansion and elicitation of memory CD4(+) T cells in vivo. Our results demonstrate that the CD24 expressed on DCs is essential neither for the induction of initial T-cell clonal expansion nor for elicitation of memory activity of primed T cells in vivo.     

Osteoblast response to hydroxyapatite doped with divalent and trivalent cations

The present in vitro study doped hydroxyapatite (HA) with various metal cations (Mg(2+), Zn(2+), La(3+), Y(3+), In(3+), and Bi(3+)) in an attempt to enhance properties of HA pertinent to orthopedic and dental applications. X-ray diffraction material characterization indicated that the metal cations may have substituted for calcium in the HA crystal structure and that all of the doped HA formulations were single-phase and crystalline. Scanning electron microscopy analysis revealed a variety of grain sizes, depending on the dopant utilized. Energy-dispersive spectroscopy confirmed that the dopants added during synthesis were present and that all of the HA formulations synthesized were within the defined range of HA phase in the CaO-P(2)O(5)-H(2)O system. Lastly, Bi-doped HA had a slower dissolution rate than either undoped HA or HA doped with other cations when exposed to simulated physiological conditions for 21 days. In terms of cell function, results provided the first evidence that osteoblasts, bone-forming cells, adhered and differentiated (as measured by alkaline phosphatase synthesis) in response to HA doped with trivalent cations (specifically, La(3+), Y(3+), In(3+), Bi(3+)) at earlier time points than either HA doped with divalent cations (Mg(2+), Zn(2+)) or undoped HA. Of the dopants examined, Bi(3+) most enhanced osteoblast long-term calcium-containing mineral deposition. For these reasons, this study revealed for the first time the potential benefits of doping HA with Bi(3+) according to criteria critical for bone prosthetic clinical success.     

Self-esteem and causal attributions for success and failure in children

In a comparison of causal attributions following success and failure in hypothetical social, athletic, and academic situations, high self-esteem grade school children were more likely than low self-esteem children to attribute their success to ability and their failure to either lack of effort or bad luck. Low self-esteem children, on the other hand, attributed their success more often than high self-esteem children to good luck (and in social situations to effort and task ease as well) and their failure to lack of ability. Whereas prior studies that focused only on the internal-external dimension found that low and high self-esteem children differed in their attributional style to success but not to failure, the present study found that when distinctions between behavioral and characterological attributions (stability and globality dimensions) were included, the two groups differed significantly in response to both success and failure. Although perhaps not generalizable beyond the present attribution measure, the most pronounced attribution differences between low and high self-esteem children were observed in the social domain, the least in the academic domain, with athletics falling in between. Finally, it was found that sex and age (within the limited fourth- to sixth-grade range examined in the present study) did not alter the overriding difference in attributional style between low and high self-esteem children.This study is based on a doctoral dissertation submitted by the first author under the supervision of the last author in partial fulfillment of the requirements for the Ph.D. degree at the University of Vermont.     

Gestational Women’s Perceptions About the Harms of Cigarette and E-Cigarette Use During Pregnancy

Objectives

The purpose of this study was to examine differences between perceived harm of cigarette and electronic cigarette (e-cigarette) use while pregnant and differences between healthcare providers’ communication about these products during pregnancy.

Methods

A convenience sample of gestational women (n?=?218; ages 18–45) living in the US completed an online survey between May and December 2017. Participants reported perceived likelihood of adverse health outcomes (e.g., low birth weight, sudden infant death syndrome) among infants/children born to mothers who used cigarettes/e-cigarettes. T-tests and two-way ANOVAs examined differences between risk perceptions of using cigarettes/e-cigarettes while pregnant based on pregnancy status (previously pregnant, currently pregnant, future pregnant). Chi-square analyses examined differences between healthcare provider communication about cigarette/e-cigarette use during pregnancy.

Results

Overall, participants believed adverse health outcomes were significantly more likely to be caused by maternal use of cigarettes than e-cigarettes. Participants who planned to be pregnant reported higher endorsement that smoking combustible cigarettes would cause a miscarriage (p?<?.05) or increased blood pressure (p?<?.05) for a child than currently pregnant participants. Participants reported healthcare providers asked about (p?<?.05), advised them not to use (p?<?.001), and talked to them about health effects of smoking combustible cigarettes while pregnant (p?<?.001) significantly more than e-cigarettes.

Conclusions for Practice

Healthcare providers working with pregnant women should perform the 5As behavioral intervention method to provide pregnant women with tobacco cessation care. They should also discuss the absolute harm nicotine exposure (via cigarettes or e-cigarettes) can have on fetal health and development.

     

Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign”

Most patients diagnosed with pancreatic cancer are classified as nonoperative candidates based on the contemporary guidelines of resectability. The advent of more potent control of systemic disease using neoadjuvant chemotherapy has enabled more aggressive operative interventions. In our multidisciplinary practice, patients with Stage III, locally advanced pancreatic cancer and superior mesenteric artery (SMA) encasement are now carefully triaged with high quality, preoperative imaging to determine if they can be considered candidates for operative resection with periadventitial dissection of the SMA. Patients displaying a “halo sign,” where the encased SMA remains fully patent and free from arterial invasion, are now candidates for SMA periadventitial dissection. This procedure involves the surgical stripping of the infiltrated neurolymphatic tissue off the SMA leaving behind a bare “skeletonized artery.” Alternatively, the “string sign” involving the SMA confers a more likely case of arterial invasion, where a complete oncologic resection cannot be achieved successfully. This method of patient selection in case of SMA involvement abandons the traditional metrics of circumferential degrees of the arterial encasement to guide surgical decisions. Our institutional approach has allowed us to meaningfully expand our operative methods of resection with the potential for improved longitudinal outcomes to pancreatic cancer patients who were deprived historically from the more effective and possibly curative treatment.     

Assembly of targeting complexes driven by a single-chain antibody

Rapid development in design and production of recombinant antibodies and antibody fragments specific for cell surface markers opens new opportunities for targeted delivery of therapeutic or imaging agents. However, the progress in this field is slowed by inactivation of many antibodies by chemical conjugation of payloads and by lack of internalization of complexes formed on the cell surface. Here, we describe conversion of a non-internalizing single chain Fv (scFv) antibody P4G7 specific for vascular endothelial growth factor receptor 2 (VEGFR-2) into a targeting protein (Hu-P4G7) for assembly of a novel type of targeting complexes. Hu-P4G7 contains an N-terminal "docking" Hu-tag, a 15-aa fragment of human RNase I, capable of high affinity binding of S-protein fragment of human RNase I or bovine RNase A. Purified Hu-P4G7 and complexes of Hu-P4G7 with S-protein bind both soluble and full-length cellular VEGFR-2. To assemble targeted DNA delivery complexes, S-protein modified with a DNA condensing agent was "docked" to Hu-P4G7, and then loaded with luciferase plasmid DNA. As expected for a non-internalizing targeting protein, Hu-P4G7-based complexes did not deliver DNA in VEGFR-2 expressing cells. However, in the presence of vascular endothelial growth factor (VEGF), these complexes selectively delivered DNA into the cells overexpressing VEGFR-2 suggesting that even a non-internalizing scFv antibody can be used for targeted intracellular drug delivery.     

Severity adjustment for length of stay: is it always necessary?

OBJECTIVE: Severity adjustment is an oft-cited requirement when comparing physicians or medical delivery systems. Each application of severity adjustment, however, has to be tested to validate the need, the method, and its value. We examined the value of severity adjustment for identifying physician outliers when studying length of stay in the hospital. DESIGN: We compared the placement of physicians in an outlier category using a severity-adjusted average length of stay (SLOS) index with their placement using the unadjusted average length of stay (ALOS). Changes in placement of the list were validated by the utilization review coordinators. SETTING: A 614-bed tertiary-care university teaching hospital. SUBJECTS: We analyzed 11,146 discharges from 138 physicians in 1992. RESULTS: The mean ALOS +/- standard deviation was 9.05 + 4.50 days, and the SLOS Index was 7.56 +/- 3.06. There were 120 inliers, 6 high outliers, and 12 low outliers by the ALOS method. Using the SLOS index, 27 of 138 physicians had their categories changed from inlier to outlier or from outlier to inlier. The difference in group changes was more significant for those going from outlier to inlier status (8/120 vs 6/18; P < .001). The patients of the six physicians whose status changed from outlier to inlier status were sicker, as indicated by the comorbidity, complications, and manifestations of disease processes score. The utilization reviewers validated the status changes in 8 of 14 instances. CONCLUSIONS: Severity-adjusted length of stay by the SLOS index appears to provide a more accurate measure than the unadjusted ALOS. The changes, however, were small. It is not clear that the added effort is worthwhile.     

Intravenous Infusion of RMP-7 Increases Ocular Uptake of Ganciclovir

Purpose. The ability of intravenous (i.v.) infusions of the bradykinin agonist, RMP-7, to permeabilize the blood-ocular barriers (BOB) to the antiviral agent ganciclovir was investigated in guinea-pigs. Methods. Different i.v. dosing regimens included pre-treatment with RMP-7 (0.2 g/kg/min for 5 min) followed by either [³H]-ganciclovir (1 Ci/0.2 ml/min) alone, and/or co-infusion with RMP-7 and [³H]-ganciclovir. At specific times the animals were sacrificed, their eyes removed, and the retina and lens epithelium dissected and analyzed for the amount of radioactivity. Results. Using the ratio of tissue vs. integrated plasma radioactivity concentration, a two-fold increase in ganciclovir steady-state levels were observed in the retina as well as lens epithelium following RMP-7 pretreatment. Peak uptake effects were achieved with a 4.5 min ganciclovir infusion. Neither longer infusions of ganciclovir alone, nor co-infusions of RMP-7 and ganciclovir further enhanced the uptake effects. Kinetic analysis indicated that RMP-7 increased the rate of ganciclovir entry (K _IN) in studied ocular tissues, while the efflux of drug (K _OUT) was not affected by this treatment. Finally, ganciclovir retina:plasma ratios elevated by RMP-7 pre-treatment, remained higher than control ratios within 60 min following cessation of 4.5 min ganciclovir infusion. Conclusions. These data offer further evidence that BOB and in particular the blood-retinal barrier can be permeabilized via bradykinin receptor stimulation. As the i.v. infusions of RMP-7 enhanced the retinal uptake of ganciclovir, it is suggested that a combination of RMP-7 and ganciclovir may provide a novel approach for treating cytomegalo-virus retinis.