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Background: Unprotected and excessive exposure to ultraviolet radiation (UVR) is the primary risk factor for skin cancer.Design: A pair-matched, group-randomized, pre-test/post-test, quasi-experimental design, with ski resorts as the unit of randomization, tested the effectiveness of Go Sun Smart, a multi-channel skin cancer prevention program. Independent samples of guests were taken at baseline (2001) and follow-up (2002); data were analyzed in 2006.Setting and Participants: A total of 6516 adult guests at 26 ski areas in the western U.S. and Canada were recruited, consented, and interviewed on chairlifts. This study was nested within an occupational intervention for ski area workers.Intervention: Ski areas were pair-matched and randomized to receive Go Sun Smart, which consisted of print, electronic, visual, and interpersonal skin cancer prevention messages.Main Outcome Measures: Sun-protection behaviors, sunburning, recall of sun-protection messages, and the association of message exposure to sun protection.Results: The difference in recall of all sun-protection messages, messages on signs and posters, and the Go Sun Smart logo was significant between the intervention and control resorts. Reported use of sun-protection practices was higher by guests at intervention ski areas using more (a higher dose of) Go Sun Smart materials. Intervention-group guests who recalled a sun-safety message were more likely to practice sun safety than intervention-group guests who did not recall a message and control-group guests.Conclusions: While the mere implementation of Go Sun Smart did not produce sun-safety improvements, Go Sun Smart appeared to be effective for guests who encountered and remembered it. Many factors can work against message exposure. Signage seemed to produce the greatest increase in exposure to sun-safety messages. [ABSTRACT FROM AUTHOR]

Abstract: Institutions of higher learning offer flexible online master of science in nursing education (MSN NE) programs to increase the number of available nursing faculty. Such programs are a viable option to degree completion; however, online programs create challenges that impact student success. This qualitative pilot study describes challenges experienced by seven enrolled or recently graduated MSN NE students. Technology, scheduling, group behaviors, faculty, curricula, and personal barriers emerged as themes. The results underscore the need to create an effective community of inquiry that fosters an environment online to promote student success., Competing Interests: The author has declared no conflict of interest., (Copyright © 2021 National League for Nursing.)

Background: The biophysical properties of red blood cells (RBCs) provide potential biomarkers for the quality of donated blood. Blood unit segments provide a simple and nondestructive way to sample RBCs in clinical studies of transfusion efficacy, but it is not known whether RBCs sampled from segments accurately represent the biophysical properties of RBCs in blood bags., Study Design and Methods: RBCs were sampled from blood bags and segments every two weeks during 8 weeks of storage at 4°C. RBC deformability was measured by deformability-based sorting using the microfluidic ratchet device in order to derive a rigidity score. Standard hematological parameters, including mean corpuscular volume (MCV), red cell distribution width (RDW), mean cell hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and hemolysis were measured at the same time points., Results: Deformability of RBCs stored in blood bags was retained over 4 weeks storage, but a progressive loss of deformability was observed at weeks 6 and 8. This trend was mirrored in blood unit segments with a strong correlation to the blood bag data. Strong correlations were also observed between blood bag and segment for MCV, MCHC, and MCH but not for hemolysis., Conclusion: RBCs sampled from blood unit segments accurately represent the biophysical properties of RBCs in blood bags but not hemolysis. Blood unit segments provide a simple and nondestructive sample for measuring RBC biophysical properties in clinical studies., (© 2021 AABB.)

Red blood cells (RBCs) stored in blood bags develop a storage lesion that include structural, metabolic, and morphologic transformations resulting in a progressive loss of RBC deformability. The speed of RBC deformability loss is donor-dependent, which if properly characterized, could be used as a biomarker to select high-quality RBC units for sensitive recipients or to provide customized storage timelines depending on the donor. We used the microfluidic ratchet device to measure the deformability of red blood cells stored in blood bags every 14 days over a span of 56 days. We observed that storage in blood bags generally prevented RBC deformability loss over the current standard 42-day storage window. However, between 42 and 56 days, the deformability loss profile varied dramatically between donors. In particular, we observed accelerated RBC deformability loss for a majority of male donors, but for none of the female donors. Together, our results suggest that RBC deformability loss could be used to screen for donors who can provide stable RBCs for sensitive transfusion recipients or to identify donors capable of providing RBCs that could be stored for longer than the current 42-day expiration window., Competing Interests: Hongshen Ma is listed as inventors on a patent related to this work., (© 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Effective immunomodulation of T-cell responses is critical in treating both autoimmune diseases and cancer. Our previous studies have demonstrated that secretomes derived from control or methoxypolyethylene glycol mixed lymphocyte alloactivation assays exerted potent immunomodulatory activity that was mediated by microRNAs (miRNA). The immunomodulatory effects of biomanufactured miRNA-based allo-secretome therapeutics (SYN, TA1, IA1 and IA2) were compared to Pan T-cell activators (PHA and anti-CD3/CD28) and lymphocyte alloactivation. The differential effects of these activation strategies on resting peripheral blood mononuclear cells (PBMC) were assessed via T-cell proliferation, subset analysis and miRNA expression profiles. Mitogen-induced PBMC proliferation (> 85%) significantly exceeded that arising from either allostimulation (~ 30%) or the pro-inflammatory IA1 secretome product (~ 12%). Consequent to stimulation, the ratio of CD4 to CD8 cells of the resting PBMC (CD4:CD8; 1.7 ± 0.1) decreased in the Pan T cell, allrecognition and IA1 activated cells (averages of 1.1 ± 0.2; 1.2 ± 0.1 and 1.0 ± 0.1). These changes arose consequent to the expansion of both CD4 + CD8 + and CD4 - CD8 - populations as well as the shrinkage of the CD4 subset and the expansion of the CD8 T cells. Importantly, these activation strategies induced vastly different miRNA expression profiles which were associated with significant differences in cellular differentiation and biological function. These findings support the concept that the "differential patterns of miRNA expression" regulate the biologic immune response in a "lock and key" manner. The biomanufacturing of miRNA-enriched secretome biotherapeutics may be a successful therapeutic approach for the systemic treatment of autoimmune diseases (TA1) and cancer (IA1)., (© 2021. The Author(s).)

Abstract: Nurse educators require information literacy (IL) to use evidence-based practices to design, develop, deliver, and evaluate education; to participate in research and scholarship of teaching and learning; and to disseminate new practices and evidence to the nursing education community. A needs assessment of students and faculty revealed knowledge deficits with IL for master of science in nursing-nurse educator students. A multidisciplinary team, guided by relevant theories, created an online applied learning and reflective tutorial to address the identified needs. Evaluation of students' participation indicated the tutorial served as an engaging resource and provided foundational knowledge of IL skills., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2021 National League for Nursing.)

Purpose: A systematic review was undertaken to characterize the training approaches that are currently being implemented in postgraduate medical education to teach residents advocacy skills., Method: An initial search was conducted in MEDLINE, PubMed, Embase, ERIC, and PsycINFO in November 2016 (updated in December 2017) for articles discussing postgraduate medical education interventions covering advocacy. Articles published between 1995 and 2017 were included. Two authors independently reviewed titles and abstracts (and, if needed, the full text) for inclusion; disagreements were resolved by consensus. Data were extracted from studies to characterize the content and pedagogy of the interventions by mapping them to the CanMEDS health advocate core competencies and key concepts., Results: A total of 3,027 unique abstracts were retrieved; 2,864 were excluded upon title and abstract review, and another 85 were excluded upon full-text review. Seventy-eight total articles were included. More studies involved residents from pediatrics, psychiatry, primary care or preventative medicine, or internal medicine than from emergency medicine, surgery, obstetrics and gynecology, or neurology. Published interventions varied widely by pedagogical approach and assessment method., Conclusions: Using the CanMEDS framework, this review maps the breadth and nature of postgraduate medical education interventions in health advocacy, with applicability to community organizations, program directors, educators, and administrators working to develop advocacy training interventions. Areas of focus included adapting practice to respond to the needs of or advocacy in partnership with patients, communities, or populations served; determinants of health; health promotion; mobilizing resources as needed; and social accountability.

The Facility for Rare Isotope Beams (FRIB) will generate many unique isotopes of scientific interest which are retained in the primary beam dump. This work uses Hollow Fiber Supported Liquid Membrane (HFSLM) for extraction of ultra-trace concentrations of short-lived radioisotopes from the large solution volumes present in the primary beam dump loop. Part per trillion levels of 48 V were successfully recovered from an aqueous solution spiked with predicted concentrations of chemically similar species, with an extraction efficiency of 71% in 60 min., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A fundamental challenge in the transfusion of red blood cells (RBCs) is that a subset of donated RBC units may not provide optimal benefit to transfusion recipients. This variability stems from the inherent ability of donor RBCs to withstand the physical and chemical insults of cold storage, which ultimately dictate their survival in circulation. The loss of RBC deformability during cold storage is well-established and has been identified as a potential biomarker for the quality of donated RBCs. While RBC deformability has traditionally been indirectly inferred from rheological characteristics of the bulk suspension, there has been considerable interest in directly measuring the deformation of RBCs. Microfluidic technologies have enabled single cell measurement of RBC deformation but have not been able to consistently distinguish differences between RBCs between healthy donors. Using the microfluidic ratchet mechanism, we developed a method to sensitively and consistently analyze RBC deformability. We found that the aging curve of RBC deformability varies significantly across donors, but is consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of cold storage in standard test tubes. The ability to distinguish between RBC units with different storage potential could provide a valuable opportunity to identify donors capable of providing RBCs that maintain their integrity, in order to reserve these units for sensitive transfusion recipients.

Background: Whole blood (WB) is held at room temperature for not more than 24 hours before blood component manufacturing. The ability of several culture collection, skin-derived, and transfusion-related bacteria to survive in WB stored at 22 ± 2°C for 24 hours was investigated in this study., Study Design and Methods: Twenty-one bacteria of the species Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus capitis, Streptococcus agalactiae, Serratia liquefaciens, Serratia marcescens, Klebsiella pneumoniae, Escherichia coli, and Yersinia enterocolitica were inoculated into 7-mL aliquots of WB at a concentration of 500 colony-forming units (CFU)/mL. Spiked WB was stored aerobically at 22 ± 2°C, and bacterial viability and growth were monitored at 3, 8, and 24 hours during WB storage. Bacteria that showed decreased viability during WB incubation were further characterized for their sensitivity to plasma factors and neutrophil killing., Results: There were three different scenarios for bacterial behavior during the hold of WB at 22 ± 2°C. Five bacteria proliferated (p < 0.03), 11 remained viable or showed low proliferation, and a third group of five bacteria had decreased or lost viability (p < 0.01). Three of the latter five bacteria were plasma-sensitive while the other two were plasma-resistant but susceptible to neutrophil killing (p = 0.01)., Conclusions: The bactericidal activity of WB can be the result of plasma sensitivity or neutrophil killing. Bacteria with a starting inoculum of 500 CFU/mL, and able to resist WB immune factors, can proliferate to clinically significant levels posing a potential safety risk to transfusion patients. Results of this pilot study should be validated under standard WB collection and storage conditions., (© 2019 AABB.)

Purpose: Implementation of employer sun safety actions was assessed in a 2-year follow-up to an occupational sun protection policy intervention., Design: Two-year follow-up assessment in a randomized pretest-posttest controlled design., Setting: Local government organizations with workers in public safety, public works, and parks and recreation., Participants: Sixty-three local government organizations (participation = 64%) and 330 frontline supervisors and 1454 workers., Intervention: Sun Safe Workplaces (SSW) intervention promoting occupational sun safety policy and education., Measures: Observations of SSW messages and sun safety items and surveys on organizations' communication and actions on sun safety., Analysis: Comparison between SSW and control groups was conducted using regression models and adjusted for clustering where appropriate, with α criterion set at P = .05 (2-tailed)., Results: At intervention worksites, more SSW messages ( P < .001) and sun safety items ( P = .025) were observed; more frontline supervisors reported organizations provided free/reduced price sunscreen ( P = .005) and communicated about sun safety ( P < .001); and more workers recalled receiving sun safety messages ( P < .001) and sun safety training ( P <.001) compared to control organizations. Implementation was greater at larger than smaller intervention organizations for wide-brimmed hats ( P = .009), long work pants ( P = .017), and shade structures ( P = .036). Older workers received the most written messages ( P = .015)., Conclusions: Sun Safe Workplaces appeared to produce actions by organizations to support employee sun safety. Large organizations may have processes, communication channels, and slack resources to achieve more implementation.

Background: Obesity is an often-cited cause of surgical morbidity. As a result, many institutions have required screening prior to "clearing" obese individuals for surgery. However, it remains unclear whether such testing is warranted for obese patients prior to upper extremity procedures. This study reviews surgical outcomes to determine if obesity does predict operative morbidity following upper extremity surgery., Methods: The National Surgical Quality Improvement Program was queried for 18 Current Procedural Terminology codes, representing upper extremity fracture and arthroplasty procedures. Patients' body mass index (BMI) and medical histories were examined as predictors for postoperative complications. Both individual and combined incidences of complications were compared between patients stratified as normal-weight (BMI < 30); obese (BMI 30-40); and morbidly obese (BMI> 40)., Results: A total of 8,477 patients were identified over the 5-year study period; 5,303 had a BMI <30, 2,565 a BMI of 30 to 40 and 585 a BMI >40. With the exception of postoperative blood transfusions, there were no significant increases in the incidence rates of any complication event as a function of BMI class. The overall incidence of complications was 2.70 % for BMI <30; 2.74 % for BMI 30 to 40; and 1.54 % for BMI >40., Conclusions: Obesity is not a reliable predictor of complications following upper extremity surgery. Thus, requiring preoperative screening for obese patients may constitute an unnecessary burden on medical resources. Further study is needed to identify specific demographics that might serve as more accurate predictors of poor outcomes in obese patients undergoing surgery of the upper extremity.

T lymphocytes play a critical role in the pro-inflammatory anti-cancer response; hence, significant pharmacologic efforts have been made to enhance the endogenous T cell response. Unfortunately, significant toxicity arises consequent to pan T cell activation. In contrast, the less robust T cell alloresponse has also demonstrated an anti-cancer effect, but poses an inherent risk of GvHD. To overcome the GvHD risk, an acellular pro-inflammatory agent (IA1) has been biomanufactured from the secretome of the allorecognition response. To assess IA1's immunomodulatory activity, T cell proliferation and differentiation were determined in vitro. The pro-inflammatory properties of the IA1 therapeutic were mediated by the miRNA-enriched fractions. Moreover, cross-species efficacy was observed consequent to the evolutionary conservation of miRNA. IA1 exerted no toxicity to resting PBMC but induced significant proliferation of resting CD3 + (CD4 + and CD8 + ) T cells and skewed the response towards a pro-inflammatory state (i.e., increased Teff:Treg ratio). Crucially, IA1-activated PBMC demonstrated a potent inhibition of cancer cell (HeLa and SH-4 melanoma) proliferation relative to the resting PBMC. The anti-proliferation effect of IA1-activated PBMC was noted within ˜12 h versus 4-5 days for resting cells. A second biomanufactured therapeutic (IA2; produced using HeLa cells) surprisingly demonstrated direct toxicity to cancer cells but was less effective than IA1 in inducing a cell-mediated response. This study demonstrates that miRNA-enriched therapeutics can be biomanufactured from the secretome and can induce a potent pro-inflammatory, anti-cancer, effect on resting lymphocytes., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: To evaluate an intervention promoting adoption of occupational sun protection policies by employers in a randomized trial., Design: A randomized pretest-posttest controlled design with 2-year follow-up was conducted in 2010 to 2013., Setting: Local government organizations in Colorado who had outdoor workers in public works, public safety, and/or parks and recreation., Participants: Ninety-eight local government organizations (n = 51 municipalities, 10 counties, and 37 special districts)., Intervention: Organizations were randomly assigned to receive a policy and education intervention comprised of personal contacts and theory-based training and materials or to an attention control group., Measures: Occupational policy documents were coded for sun safety content by a trained research assistant blind to condition., Analysis: Policy scores were analyzed with logistic and Poisson regression models using imputation., Results: At posttest, more organizations in the intervention group had a sun protection policy than in the control group (odds ratio [OR] = 4.91, P < .05; intent to treat: OR = 5.95, P < .05) and policies were more extensive (χ 2 = 31.29, P < .01; intent to treat: χ 2 =73.79, P < .01) and stronger (χ 2 = 24.50, P < .01; intent to treat: χ 2 = 51.95, P < .01). Policy adoption was higher when the number of contacts and trainings increased ( P < .05)., Conclusion: The intervention had a large effect on adoption of formal sun protection policies, perhaps because of its fit with legal requirements to maintain safe workplaces. Personal contacts with managers were influential on adoption of occupational policy even in this age of communication technology and social media.

Despite the critical importance of mechanical (rheological + extrudability) deformability in the vascular flow of lymphocytes, it has been poorly investigated due to the limitations of existing technological tools. Microfluidics analysis of leukocyte deformability offers significant advantages in that it offers high throughput, large sample population and the ability to analyze a heterogeneous population. These advantages are in stark contrast to previous approaches that focused on single cell measurements. Importantly, the flow characteristics of microfluidic devices more closely model vascular deformability in that shear stress is applied forcing leukocyte passage through micropores of designed size. The modeling of vascular flow has been further enhanced by the development of a microfluidic ratchet device that introduced an oscillatory flow. As demonstrated in this study, the microfluidic ratchet device was able to separate human peripheral blood leukocyte subsets (i.e., monocytes and lymphocytes) based on differential deformability profiles. Furthermore, morphologically similar lymphocyte subsets (CD4, CD8 and NK) could also be separated. The subset separation was observed to be largely due to differences in their intracellular complexity (i.e., granule content) with granule-positive T lymphocytes and NK cells being less deformable than granule-negative lymphocytes. Moreover, upon immune activation, deformability of the de-granulated lymphocytes increased consequent to the decrease in cytoplasmic granularity/viscosity. This study for the first time demonstrates that leukocytes subsets have differential deformability profiles and that intracellular granularity/degranulation significantly impacts the lymphocytes' mechanical properties. These findings could be of clinical value as biomarkers of lymphocyte activation state and potential disease processes.

Taking vacations in sunny locations is associated with the development of skin cancer. This study tested a multi-component sun protection intervention based on diffusion of innovations theory and transportation theory designed to increase vacationers' comprehensive sun protection, i.e., use of clothing, hats, and shade, and use, pre-application, and reapplication of sunscreen. The trial enrolled 41 warm weather resorts in North America in a pair-matched group randomized pretest-posttest design and assessed samples of adult vacationers at resort outdoor recreation venues regarding sun protection at pretest (n = 3,531) and posttest (n = 3,226). While results showed no overall effect of the intervention on comprehensive sun protection across venues, the intervention produced statistically significant improvements in sun protection at waterside venues (pools and beaches). The intervention's overall effects may have been impeded by a lack of uniformly robust implementation, low interest in skin cancer prevention by guests, or shortcomings of the theories used to create prevention messages. The intervention may have worked best with guests in the highest-risk recreation venue, i.e., waterside recreation where they exposed the most skin. Alternative approaches that alter resort organizations, such as through changes in policy, environmental features, or occupational efforts might be more effective than targeting vacationers with behavior-change messages.

T cell-mediated immune rejection remains a barrier to successful transplantation. Polymer-based bioengineering of cells may provide an effective means of preventing allorecognition and the proliferation of cytotoxic (CD8 + ) T lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers, the effects of leukocyte immunocamouflage on CD8 + and CD4 + alloproliferation and T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction (MLR) model. Polymer-grafting effectively camouflaged multiple leukocyte markers (MHC class I and II, TCR and CD3) essential for effective allorecognition. Consequent to the polymer-induced immunocamouflage of the cell membrane, both CD8 + and CD4 + T cell alloproliferation were significantly inhibited in a polymer dose-dependent manner. The loss of alloproliferation correlated with the induction of Treg cells (CD4 + CD25 + Foxp3 + ). The Tregs, surprisingly, arose primarily via differentiation of naive, non-proliferating, CD4 + cells. Of biologic importance, the polymer-induced Treg were functional and exhibited potent immunosuppressive activity on allogeneic CTL proliferation. These results suggest that immunocamouflage-mediated attenuation of alloantigen-TCR recognition can prevent the tissue destructive allogeneic CD8 + T cell response, both directly and indirectly, through the generation/differentiation of functional Tregs. Immunocamouflage induced tolerance could be clinically valuable in attenuating T cell-mediated transplant rejection and in the treatment of autoimmune diseases., Statement of Significance: While our previous studies have demonstrated that polymer-grafting to MHC disparate leukocytes inhibits CD4 + cell proliferation, the effects of PEGylation on the alloproliferation of CD8 + cytotoxic T cells (CTL) was not examined. As shown here, PEGylation of allogeneic leukocytes prevents the generation of the CTL response responsible for acute rejection. The loss of CTL proliferation is consequent to the polymer-based attenuation of allorecognition and the induction of T regulatory cells (Tregs). Interestingly, the Tregs are primarily generated via the differentiation of non-proliferating naive T cells. Importantly, the Tregs are functional and effectively induce a tolerogenic environment when transferred to an alloresponsive environment. The use of polymer-modified leukocytes provides a unique approach to effectively maximize the biologic production of functional Tregs both in vitro and in vivo. By using this approach it may be possible to attenuate unwanted alloresponses (e.g., graft rejection) or to treat autoimmune diseases., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To ascertain whether strategies of treatment with a biological disease-modifying antirheumatic drug (bDMARD) are cost-effective in an English setting. Results are presented for those patients with moderate to severe rheumatoid arthritis (RA) and those with severe RA., Methods: An economic model to assess the cost-effectiveness of 7 bDMARD was developed. A systematic literature review and network metaanalysis was undertaken to establish relative clinical effectiveness. The results were used to populate the model, together with estimates of Health Assessment Questionnaire (HAQ) score following European League Against Rheumatism response; annual costs, and utility, per HAQ band; trajectory of HAQ for patients taking bDMARD; and trajectory of HAQ for patients using nonbiologic therapy (NBT). Results were presented as those associated with the strategy with the median cost-effectiveness. Supplementary analyses were undertaken assessing the change in cost-effectiveness when only patients with the most severe prognoses taking NBT were provided with bDMARD treatment. The costs per quality-adjusted life-year (QALY) values were compared with reported thresholds from the UK National Institute for Health and Care Excellence of £20,000 to £30,000 (US$24,700 to US$37,000)., Results: In the primary analyses, the cost per QALY of a bDMARD strategy was £41,600 for patients with severe RA and £51,100 for those with moderate to severe RA. Under the supplementary analyses, the cost per QALY fell to £25,300 for those with severe RA and to £28,500 for those with moderate to severe RA., Conclusion: The cost-effectiveness of bDMARD in RA in England is questionable and only meets current accepted levels in subsets of patients with the worst prognoses.

Hemolytic anemia is one of the hallmarks of malaria and leads to an increase in oxidized heme (hemin) within the plasma of infected individuals. While scavenger proteins sequester much of the circulating heme, it has been hypothesized that extracellular heme may play a central role in malaria pathogenesis. We have previously developed the multiplex fluidic plunger (MFP) device for the measurement of red blood cell (RBC) deformability. Here, we demonstrate that the measurement of changes in RBC deformability is a sensitive method for inferring heme-induced oxidative stress. We further show that extracellular hemin concentration correlates closely with changes in RBC deformability and we confirm that this biophysical change correlates with other indicators of cell stress. Finally, we show that reduced erythrocyte deformability corresponds with both erythrophagocytosis and RBC osmotic fragility. The MFP microfluidic device presents a simple and potentially inexpensive alternative to existing methods for measuring hemolytic cell stress that could ultimately be used to perform clinical assessment of disease progression in severe malaria.

During vacations, many individuals receive high-risk sun exposure that is associated with skin cancer. Vacationers in outdoor recreation venues (pretest n=4347; posttest n=3986) at warm-weather destination resorts in North America (n=41) were enrolled in a pair-matched, group-randomized pretest-posttest controlled quasi-experimental design in 2012-14. Print, audiovisual, and online messages based on Transportation Theory and Diffusion of Innovation Theory and promoting advanced sun protection (e.g., use of clothing, hats, shade and pre-application/reapplication of sunscreen and reliable cues to high UV) were delivered through resort channels. Vacationers' sun protection practices observed by trained research staff (i.e., body coverage and shade use analyzed individually and in combined scores) did not differ by experimental condition (p>0.05) or intervention implementation (p>0.05). However, recreation venue moderated intervention impact. The intervention improved sun protection at waterside recreation venues (z-score composite: intervention pre=-22.74, post=-15.77; control pre=-27.24, post=-23.24) but not non-waterside venues (z-score composite: intervention pre=20.43, post=20.53; control pre=22.94, post=18.03, p<0.01). An additional analysis showed that resorts with greater program implementation showed more improvements in sun protection by vacationers at waterside (z=score composite: high implementation pre=-25.45, post=-14.05; low implementation pre=-24.70, post=-21.40) compared to non-waterside (z-score composite: high implementation pre=14.51, post=19.98; low implementation pre=24.03, post=18.98, p<0.01) recreation venues. The intervention appeared effective with the vacationers in recreation venues with the highest-risk for sun exposure, waterside venues. However, it was not effective throughout all the resort venues, possibly because of the sun-seeking desires of vacationers, information overload at the resorts, and constraints on clothing styles and sun protection by recreation activity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The immunocamouflage of non-ABO blood group antigens by membrane-grafted methoxypoly(ethylene glycol) (mPEG) may attenuate the risk of red blood cell (RBC) alloimmunization. However, concerns have been raised over the immunogenic risk of PEG and PEG-RBCs. To assess this risk, murine and human studies were performed. Mice were exposed to soluble PEG prior to, or between, multiple transfusions (∼60-day intervals) of control or mPEG-RBCs, and cell survival was determined by flow cytometry. In some studies, the control and mPEG-RBC groups were reversed after one or more transfusions. Furthermore, human blood donors and commercial intravenous immunoglobulin products were examined to detect anti-PEG antibodies and to assess the risk for false positives. Naïve mice receiving chronic mPEG-RBC transfusions had normal RBC survival curves with no evidence of anti-PEG antibodies. Similarly, challenge with soluble PEG did not elicit anti-PEG antibodies in mice. Studies in humans revealed no evidence of a high prevalence of anti-PEG antibodies in either blood donors or commercial intravenous immunoglobulin. However, by use of the methods employed by studies identifying high levels of anti-PEG antibodies, a significant level (∼15%) of "false positives" were detected in commercial antibodies of known (non-PEG) specificities. These findings suggest that methodologic problems yielded a high rate of false positives in these earlier studies. These data continue to support the clinical utility of cellular PEGylation and the low immunogenic risk of grafted mPEG., (Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to solar ultra violet radiation (UVR) is a primary risk factor for skin cancer. Vacationers often fail to protect themselves from harmful UVR., Purpose: The study assessed the sun protection practices of resort guests in various outdoor leisure and recreation venues during warm-weather seasons., Method: 41 North American resorts were enrolled in a quasi-experimental randomized controlled trial. Adult guests were observed (n=4091) and surveyed (n=3694) in a cross sectional sample. Data collection was conducted in recreation and leisure venues with outdoors commons/reception areas acting as the comparison condition., Results: The mean percent of vacationers at pools and beaches were more likely (p < 0.001) to wear sunscreen than in commons areas but less likely (p < 0.001) to wear cover-up clothing or use shade. In both samples, the combined sun protection scores were higher in commons areas compared to all venues except for outdoor dining (p < 0.001)., Discussion: Sun safety was suboptimal in all venues and was potentially mitigated by venue type., Translation to Health Education Practice: Approaches are needed to encourage vacationers to practice comprehensive sun protection and to work with resorts to construct built environments that facilitate rather than act as barriers to sun safety.

Background: Individual variables and area-level variables have been identified as explaining much of the variance in rates of compulsory in-patient treatment., Aims: To describe rates of voluntary and compulsory psychiatric in-patient treatment in rural and urban settings in England, and to explore the associations with age, ethnicity and deprivation., Method: Secondary analysis of 2010/11 data from the Mental Health Minimum Dataset., Results: Areas with higher levels of deprivation had increased rates of in-patient treatment. Areas with high proportions of adults aged 20-39 years had the highest rates of compulsory in-patient treatment as well as the lowest rates of voluntary in-patient treatment. Urban settings had higher rates of compulsory in-patient treatment and ethnic density was associated with compulsory treatment in these areas. After adjusting for age, deprivation and urban/rural setting, the association between ethnicity and compulsory treatment was not statistically significant., Conclusions: Age structure of the adult population and ethnic density along with higher levels of deprivation can account for the markedly higher rates of compulsory in-patient treatment in urban areas., (© The Royal College of Psychiatrists 2016.)

Background: Vacationing at sunny, warm weather locations is a risk factor for excessive solar ultraviolet (UV) radiation exposure and skin cancer., Objectives: This study examined the association of environmental variables related to UV levels with vacationers' sun protection., Methods: Vacationers at 41 summer resorts in 17 states and 1 Canadian Province were interviewed (n=3531) and observed (N=4347) during 2012 and 2013. Clothing coverage, sunglasses, and shade use were observed. Use of sunscreen and sunburns were self-reported. Environmental information was recorded by research staff or acquired from ground stations and the weather service., Results: Temperature was positively associated with sun protection behaviors; however clothing coverage was negatively associated with temperature. Cloud cover was negatively associated with sun protection, with the exception of clothing coverage which was positively associated with it. Elevation showed a mixed pattern of associations with vacationer's sun protection. Latitude of a resort was negatively associated with most sun protection behaviors, such that sun protection increased at more southerly resorts. Similarly, the farther south a vacationer traveled to the resort, the less sun protection they employed. The UV index showed a weak, positive relationship with some sun protection behaviors even when controlling for temperature., Conclusions: Vacationers appeared aware that UV is higher at southern latitudes and may learn UV is intense when living in southern regions. However, many used temperature, an unreliable cue, to judge UV intensity and seemed to adjust clothing for warmth not UV protection. Efforts are needed to help individuals make more accurate sun safety decisions., (Copyright © 2016. Published by Elsevier Inc.)

Considering the systemic toxicity of chemotherapeutic agents, there is an urgent need to develop new targeted drug delivery systems. Herein, we have developed a new nuclear targeted, redox sensitive, drug delivery vehicle to simultaneously deliver the anticancer drugs gemcitabine and doxorubicin to the nuclei of pancreatic cancer cells. We prepared polymeric bilayer vesicles (polymersomes), and actively encapsulated the drug combination by the pH gradient method. A redox-sensitive polymer (PEG-S-S-PLA) was incorporated to sensitize the formulation to reducing agent concentration. Acridine orange (AO) was conjugated to the surface of the polymersomes imparting nuclear localizing property. The polymersomes' toxicity and efficacy were compared with those of a free drug combination using monolayer and three-dimensional spheroid cultures of pancreatic cancer cells. We observed that the redox sensitive, nuclear-targeted polymersomes released more than 60% of their encapsulated contents in response to 50 mM glutathione. The nanoparticles are nontoxic; however, the drug encapsulated vesicles have significant toxicity. The prepared formulation can increase the drug's therapeutic index by delivering the drugs directly to the cells' nuclei, one of the key organelles in the cells. This study is likely to initiate research in targeted nuclear delivery using other drug formulations in other types of cancers.

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.

Tissue rejection occurs subsequent to the recognition of foreign antigens via receptor-ligand contacts between APC (antigen presenting cells) and T cells, resulting in initialization of signaling cascades and T cell proliferation. Bioengineering of donor cells by the covalent attachment of methoxypolyethylene glycol (mPEG) to membrane proteins (PEGylation) provides a novel means to attenuate these interactions consequent to mPEG-induced charge and steric camouflage. While previous studies demonstrated that polymer-mediated immunocamouflage decreased immune recognition both in vitro and in vivo, these studies monitored late events in immune recognition and activation such as T cell proliferation. Consequently little information has been provided concerning the early cellular events governing this response. Therefore, the effect of PEGylation was assessed by examining initial cell-cell interactions, changes to activation pathways, and apoptosis to understand the role that each may play in the decreased proliferative response observed in modified cells during the course of a mixed lymphocyte reaction (MLR). The mPEG-modified T cells resulted in significant immunocamouflage of lymphocyte surface proteins and decreased interactions with APC. Furthermore, mPEG-MLR exhibited decreased NFκB pathway activation, while exhibiting no significant differences in degree of cell death compared to the control MLR. These results suggest that PEGylation may prevent the direct recognition of foreign alloantigens by decreasing the stability and duration of initial cell-cell interactions., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Exposure to solar ultraviolet radiation during recreation is a risk factor for skin cancer. A trial evaluated an intervention to promote advanced sun protection (sunscreen pre-application/reapplication; protective hats and clothing; use of shade) during vacations., Materials and Methods: Adult visitors to hotels/resorts with outdoor recreation (i.e., vacationers) participated in a group-randomized pretest-posttest controlled quasi-experimental design in 2012-14. Hotels/resorts were pair-matched and randomly assigned to the intervention or untreated control group. Sun. protection (e.g., clothing, hats, shade and sunscreen) was measured in cross-sectional samples by observation and a face-to-face intercept survey during two-day visits., Results: Initially, 41 hotel/resorts (11%) participated but 4 dropped out before posttest. Hotel/resorts were diverse (employees=30 to 900; latitude=24° 78' N to 50° 52' N; elevation=2ft. to 9726ft. above sea level), and had a variety of outdoor venues (beaches/pools, court/lawn games, golf courses, common areas, and chairlifts). At pretest, 4347 vacationers were observed and 3531 surveyed. More females were surveyed (61%) than observed (50%). Vacationers were mostly 35-60years old, highly educated (college education=68%) and non-Hispanic white (93%), with high-risk skin types (22%). Vacationers reported covering 60% of their skin with clothing. Also, 40% of vacationers used shade; 60% applied sunscreen; and 42% had been sunburned., Conclusions: The trial faced challenges recruiting resorts but result showed that the large, multi-state sample of vacationers were at high risk for solar UV exposure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes.

The Rh D antigen posed both a significant clinical risk and inventory supply issue in transfusion medicine. The successful development of the immunocamouflaged RBC has the potential to address both the risk of acute anti-D transfusion reactions and to improve D- blood inventory in geographic locations where D- blood is rare (e.g., China). The immunocamouflage of RBC was mediated by the covalent grafting of methoxy(polyethylene glycol) to the cell membrane thereby obscuring the D protein from the immune system. To determine the potential efficacy of mPEG-D+ RBC in D- recipients, anti-D alloantibodies from previously alloimmunized individuals were utilized. The effects of polymer chain size (2-30 kDa) and grafting concentration (0-4 mM) on antibody binding and erythrophagocytosis were determined using the clinically validated monocyte monolayer assay (MMA) and flow cytometry. The immunocamouflage of D was polymer size and grafting concentration dependent as determined using human anti-D alloantibodies (both pooled [RhoGAM] and single donors). Importantly, the 20 kDa polymer provided excellent immunocamouflage of D and reached a clinically significant level of protection, as measured by the MMA, at grafting concentrations of ≥1.5 mM. These findings further support the potential use of immunocamouflaged RBC to reduce the risk of acute transfusion reactions following administration of D+ blood to D- recipients in situations where D- units are unavailable or supply is geographically constrained., (© 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.)

The sustainability of evidence-based programs is needed to obtain long-term benefits. To assess sustainability of Go Sun Smart (GSS), an occupational skin cancer prevention program disseminated to the North American ski industry. Fifty-three of the 68 ski areas from the original dissemination trial participated in 2012 and 2013, 5 to 7 years after program distribution by enhanced or basic dissemination strategies. Sustained use was measured by: (1) on-site observation of sun protection communication and (2) an online survey with senior managers. In the sustainability assessment, sun safety communication had declined, and dissemination strategy did not affect continued use. Managers held weaker attitudes about skin cancer importance and program fit, but more managers provided free/reduced-cost sunscreen than in the dissemination trial. Manager turnover was a key factor in program discontinuance. Sustainability remains a challenge. Additional research is needed to determine the best strategies for sustainability.

A key challenge in transfusion medicine research and clinical hematology is to develop a simple and non-destructive method to measure the quality of each blood unit prior to use. RBC deformability has long been proposed as an indicator of blood quality. We measured RBC deformability using the pressure required for single cells to transit through a micrometer scale constriction to examine longitudinal changes in RBC deformability, as well as the variability in blood quality and storage capacity across donors. We used a microfluidic device to monitor deformability changes in RBCs stored in plastic tubes and in blood bags over 14 and 56 days respectively. We found consistent storage based degradation of RBC deformability with statistically significant variability in both the initial RBC deformability and storage capacity among donors. Furthermore, all samples exhibited a transient recovery phenomenon. Deformability profiling of stored RBCs using transiting pressure showed significant donor variability in initial quality and storage capacity. This measurement approach shows promise as a rapid method to individually assess the quality of stored RBC units., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Sustainability of prevention programs is a public health goal., Methods: The effectiveness of Go Sun Smart, an occupational skin cancer prevention program, was evaluated 5 to 7 years out from the conclusion of a controlled randomized dissemination trial that compared an enhanced versus basic dissemination strategy at 53 ski areas enrolled in the trial., Results: Employees (n = 2940) at ski areas in the enhanced condition reported fewer sunburns but did not differ from employees in the basic condition on other sun-protection measures. Significant differences for all sun-protection practices were identified at ski areas that displayed nine or more Go Sun Smart materials or a combined total of nine or more Go Sun Smart and other sun safety messages., Conclusions: Exposure to prevention messages is an important determinant of program effectiveness and potentially of program sustainability.

Importance: Skin cancer prevention remains a national priority. Reducing chronic UV radiation exposure for outdoor workers through sun-safety practices is an important step to help reduce the incidence of skin cancer., Objective: To determine the presence of occupational sun-safety policies at local government organizations in a single state., Design, Setting, and Participants: Of 571 potentially eligible local government organizations of Colorado cities, counties, and special tax districts, we enrolled 98 in a randomized pretest-posttest controlled experiment starting August 15, 2010, that evaluated an intervention to promote the adoption of sun-safety policies. We used a policy-coding protocol to evaluate personal sun-protection practices, environmental and administrative controls, and policy directives for sun safety starting February 10, 2011. We report the baseline assessment of the occupational sun-protection policies of these organizations., Main Outcomes and Measures: The presence of an occupational sun-safety policy., Results: Overall, 85 local government organizations (87%) had policies that required personal sun-protection practices, including the use of eyewear, hats, and protective clothing. However, of the 98 responding organizations, only 8 hat policies (8%), 10 eyewear policies (10%), and 7 clothing policies (7%) mentioned sun protection as the intent of the policy. Only cosmopoliteness, operationalized as proximity to an urban area, was associated with the presence of a sun-safety policy (odds ratio, 0.99 [95% CI, 0.98-1.00]; P = .02)., Conclusions and Relevance: Outdoor workers are at increased risk for skin cancer because of long-term exposure to solar UV radiation. Although organizational policies have the potential to increase sun protection in occupational settings, occupational sun-safety policies were uncommon among local governments. Opportunities exist for dermatologists and other physicians to influence occupational sun-safety practices and policies, which are consistent with other safety procedures and could easily be integrated into existing workplace practices.

Health promotion programs that develop and implement strategies to promote sun safety practices to children have the potential to reduce skin cancer occurrence later in life. Go Sun Smart (GSS), a sun safety program for employees and guests of ski areas, was distributed to determine if an enhanced dissemination strategy was more effective than a basic dissemination strategy at reaching parents at ski and snowboard schools. On-site observations of GSS use and surveys of 909 parents/caregivers with children enrolled in ski and snowboard schools at 63 ski areas were conducted and analyzed using techniques for clustered designs. No differences were identified by dissemination strategy. Greater implementation of GSS (>5 messages posted) was associated with greater parental recall, 36.6% versus 16.7%, of materials, but not greater sun protection practices. Greater recall of messages, regardless of level of implementation, resulted in greater sun protection practices including applying sunscreen (p < .05), providing sunglasses and goggles (p < .01), and more use of all sun protection practices (p < .01). Ski areas with more program materials appeared to reach parents with sun safety advice and thus convinced them to take more precautions for their children. Sun safety need not be at odds with children's outdoor recreation activities., (© 2015 Society for Public Health Education.)

Context: Outdoor workers are especially susceptible to skin cancer--the most common, but also one of the most preventable, forms of cancer. Colorado, the location of the study, has the second highest rate of skin cancer deaths in the nation., Objective: Local government managers in Colorado-in municipalities, counties, and special districts-were surveyed to ascertain the extent to which they engage in formal (written) and informal practices to protect their outdoor workers against excessive exposure to sun., Design: The survey consisted of 51 questions assessing awareness of formal or informal practices for sun protection of outdoor workers. An index of practices--the study's dependent variable--was created that was composed or practices such as providing employees free or reduced-cost sunscreen, wide-brimmed hats, sunglasses, long-sleeved work shirts, long work pants, and temporary or permanent outdoor shade shelters. Proscriptive policies, such as restricting the use of broad brimmed hats, were subtracted from the index. Surveys were completed by 825 administrators representing 98 jurisdictions. Responses from administrators in the same jurisdiction were averaged., Results: More than 40% of responding jurisdictions indicated that they engaged in informal sun safety practices. Tests conducted to determine what variables might account for the adoption of these sun protection practices found that the degree to which a community could be regarded as cosmopolite and as having an individualistic political culture were significant predictors. Type of government was also significant. Although, higher community income was a significant predictor, neither local government budget nor size was significant., Conclusions: The adoption of sun safe practices bears low costs with potentially high returns. Findings from this study suggest that awareness campaigns might most effectively target cosmopolite communities, but that the greatest impact might be achieved by targeting localite communities. Government size and budget do not appear to be constraints in the adoption of sun safe practices.

Go Sun Smart is a theory-based health communication program designed to influence sun-protection behaviors of employees and guests at high-altitude ski areas to reduce skin cancer risk. The effects of Go Sun Smart, in a Phase IV dissemination randomized posttest-only trial, on sun-protection behaviors of ski area guests are reported. Program use was assessed by on-site observation and guest message exposure, and sun protection was measured in intercept surveys at ski areas. Dissemination strategy-enhanced versus basic-was not significantly related to sun safety practices. Additional analyses examined the relation between message exposure and guests' sun safety practices. Ski areas displaying at least 6 Go Sun Smart materials in guest-only areas and 9 Go Sun Smart materials throughout the area increased guests' message exposure. Higher message exposure within the high-use ski areas was associated with improved sun protection by guests but not within the low-use ski areas. The authors underscore the importance of program implementation and message exposure on the success of evidence-based health communication efforts applied industrywide.

A common indicator of rheological dysfunction is a measurable decrease in the deformability of red blood cells (RBCs). Decreased RBC deformability is associated with cellular stress or pathology and can impede the transit of these cells through the microvasculature, where RBCs play a central role in the oxygenation of tissues. Therefore, RBC deformability has been recognized as a sensitive biomarker for rheological disease. In the current study, we present a strategy to measure RBC cortical tension as an indicator of RBC deformability based on the critical pressure required for RBC transit through microscale funnel constrictions. By modeling RBCs as a Newtonian liquid drop, we were able to discriminate cells fixed with glutaraldehyde concentrations that vary as little as 0.001%. When RBCs were sampled from healthy donors on different days, the RBC cortical tension was found to be highly reproducible. Inter-individual variability was similarly reproducible, showing only slightly greater variability, which might reflect biological differences between normal individuals. Both the sensitivity and reproducibility of cortical tension, as an indicator of RBC deformability, make it well-suited for biological and clinical analysis of RBC microrheology., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The grafting of low-immunogenic polymers to cells dramatically reduces antigenic recognition and immunogenicity of allogeneic donor cells consequent to steric and charge camouflage (i.e., immunocamouflage). While methoxypoly(ethylene glycol) [mPEG] has historically been utilized for the immunocamouflage of cells, other low-immunogenic polymers such as polyethyloxazoline propionic acid (PEOZ) may also be capable of conferring immunoprotection. Moreover, PEOZ may have attributes that could have enhanced pharmacological and biological utility relative to mPEG. To evaluate the immunocamouflage efficacy of PEOZ relative to mPEG, human red blood cells (RBC) and leukocytes were modified with mPEG or PEOZ. The differential effects of mPEG and PEOZ was assessed via grafting efficacy, cell morphology and viability, immunocamouflage of surface antigens, and the prevention of in vitro immune recognition (RhD and HLA). Although membrane grafting of mPEG and PEOZ were similar, mPEG demonstrated superior immunocamouflage efficacy as measured by antibody binding and phagocytosis of opsonized RBC while PEOZ showed improved RBC morphology. While mPEG appears to be superior to PEOZ in the immunocamouflage of cells, PEOZ may still be a valuable addition to our repertoire of immunomodulatory polymers. Moreover, our results demonstrate the importance of indirect immunocamouflage of antigens found in membrane protein complexes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Malignant melanoma is an aggressive cutaneous neoplasm whose incidence has continued to increase worldwide. Currently, histopathologic examination of specimens is the gold standard for the diagnosis and categorization of melanoma. Cytogenetic analysis represents a powerful, and currently underused, adjunct to traditional histologic examination in distinguishing nevi and melanomas. Chromosomal studies have shown that malignant melanomas often contain multiple chromosomal alterations, most commonly of chromosomes 1, 6, 7, 9, 10 and 11. These chromosomes often include genes within the MAPK molecular pathway, which is involved in the development and progression of melanoma. Fluorescence in situ hybridization (FISH) can detect a number of recurrent anomalies, and commercially available kits for melanoma detection have been devised. The utility of cytogenetics in melanocytic lesions at certain anatomic sites has been evaluated, including acral lesions, uveal lesions, and lymph node metastases. Recurring cytogenetic anomalies have been defined in various challenging histologic subtypes, such as desmoplastic melanomas and Spitzoid lesions. Cytogenetic analysis may also be used to provide supplementary information in prognostication, particularly in uveal melanomas. We provide a brief review of the molecular pathways found in melanoma and a summary of what is known and remains unknown regarding cytogenetic aberrations associated with malignant melanoma.

Microfluidic analysis of blood has potential clinical value for determining normal and abnormal erythrocyte deformability. To determine if a microfluidic device could reliably measure intra- and inter-personal variations of normal and oxidized human red blood cell (RBC), venous blood samples were collected from repeat donors over time. RBC deformability was defined by the cortical tension (pN/µm), as determined from the threshold pressure required to deform RBC through 2-2.5 μm funnel-shaped constrictions. Oxidized RBC were prepared by treatment with phenazine methosulphate (PMS; 50 µM). Analysis of the control and oxidized RBC demonstrated that the microfluidic device could clearly differentiate between normal and mildly oxidized (20.13 ± 1.47 versus 27.51 ± 3.64 pN/µm) RBC. In vivo murine studies further established that the PMS-mediated loss of deformability correlated with premature clearance. Deformability variation within an individual over three independent samplings (over 21 days) demonstrated minimal changes in the mean pN/µm. Moreover, inter-individual variation in mean control RBC deformability was similarly small (range: 19.37-21.40 pN/µm). In contrast, PMS-oxidized cells demonstrated a greater inter-individual range (range: 25.97-29.90 pN/µm) reflecting the differential oxidant sensitivity of an individual's RBC. Importantly, similar deformability profiles (mean and distribution width; 20.49 ± 1.67 pN/µm) were obtained from whole blood via finger prick sampling. These studies demonstrated that a low cost microfluidic device could be used to reproducibly discriminate between normal and oxidized RBC. Advanced microfluidic devices could be of clinical value in analyzing populations for hemoglobinopathies or in evaluating donor RBC products post-storage to assess transfusion suitability., (Copyright © 2013 Wiley Periodicals, Inc.)

Modulation of cell surface properties via functional modification is of great interest in cell-based therapies, drug delivery, and in transfusion. We study the in vivo circulation, immuogenicity, and mechanism of clearance of hyperbranched polyglycerol (HPG)-modified red blood cells (RBCs) as a function of molecular properties of HPGs. The circulation half-life of modified cells can be modulated by controlling the polymer graft concentration on RBCs; low graft concentrations (0.25 and 0.5 mM) showed normal circulation as that of control RBCs. Molecular weight of HPG did not affect the circulation of modified RBCs. HPG grafting on RBCs reduced CD47 self-protein accessibility in a graft concentration-dependent fashion. HPG-grafted RBCs are not immunogenic, as is evident from their similar circulation profile upon repeated administration in mice and monitoring over 100 days. Histological examination of the spleen, liver, and kidneys of the mice injected with modified RBCs revealed distinct differences, such as elevated iron deposits and an increase in the number of CD45 expressing cells at high graft concentration of HPGs (1.5 mM); no changes were seen at low graft concentration. The absence of iron deposits in the white pulp region of the spleen and its presence in the red pulp region indicates that the clearance of functional RBCs occurs in the venous sinuses mechanical filtering system, similar to the clearance of unmodified senescent RBCs. HPG modification at grafting concentrations that yield long circulation in mice produced camouflage of a large number of minor blood group antigens on human RBCs, demonstrating its utility in chronic transfusion. The normal circulation, nonimmunogenic nature, and the potential to modulate the circulation time of modified cells without toxicity make this HPG-based cell surface modification approach attractive for drug delivery and other cell-based therapies.

SPARC is a web-based research management system that integrates both research and routine clinical care work flows and has now been in operation at the Medical University of South Carolina (MUSC) since March 1, 2012. The system provides a one-stop-shop to researchers for all service requests related to their research with a focus on billing compliance, proposal and budget development, and work fulfillment data collection. Upgrades and enhancements based on user feedback from institutions around the country include increased invoicing and billing functionality, clinical research visit and assessment tracking, and outcome assessment using grant and publication data links. System development leverages home grown and community open source components.

Red blood cell (RBC) transfusion is vital for the treatment of a number of acute and chronic medical problems such as thalassemia major and sickle cell anemia. Due to the presence of multitude of antigens on the RBC surface (~308 known antigens), patients in the chronic blood transfusion therapy develop alloantibodies due to the miss match of minor antigens on transfused RBCs. Grafting of hydrophilic polymers such as polyethylene glycol (PEG) and hyperbranched polyglycerol (HPG) forms an exclusion layer on RBC membrane that prevents the interaction of antibodies with surface antigens without affecting the passage of small molecules such as oxygen, glucose, and ions. At present no method is available for the generation of universal red blood donor cells in part because of the daunting challenge presented by the presence of large number of antigens (protein and carbohydrate based) on the RBC surface and the development of such methods will significantly improve transfusion safety, and dramatically improve the availability and use of RBCs. In this report, the experiments that are used to develop antigen protected functional RBCs by the membrane grafting of HPG and their characterization are presented. HPGs are highly biocompatible compact polymers, and are expected to be located within the cell glycocalyx that surrounds the lipid membrane and mask RBC surface antigens.

Herein, we report the application of synthesized fluorescent, water soluble polymers for post-translational subtyping and differentiation of breast cancer cells in vitro. The fluorescence emission spectra from these polymers were modulated differently in the presence of conditioned cell culture media from various breast cancer cells. These polymers differentiate at a post-translation level possibly due to their ability to interact with extracellular enzymes that are over-expressed in cancerous conditions.