Three-dimensional gradient index microlens arrays for light-field and holographic imaging and displays.

The geometric, intensity, and chromatic distortions that are a result of the limitations of the material and processes used to fabricate micro-optical lens arrays (MLAs) degrade the performance of light-field systems. To address these limitations, inkjet print additive manufacturing is used to fabricate planar gradient index (GRIN) lenslet arrays, in which volumetric refractive index profiles are used to embed optical functions that would otherwise require multiple homogeneous index MLA surfaces. By tailoring the optical ink feedstock refractive index spectra, independent control over dispersion is achieved, and achromatic performance is made possible. Digital manufacturing is shown to be beneficial for optimizing individual micro-optical channels in arrays wherein the shape, size, aspect ratio, focal length, and optical axis orientation of the lenslets vary as a function of the position within the optical field. Print fabrication also allows opaque inter-lens baffling and aperture stops that reduce inter-channel cross talk, improve resolution, and enhance contrast. These benefits are demonstrated in a light-field display testbed.

Effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface: A quantitative systematic review.

BACKGROUND: Globally, chronic disease is a leading cause of illness, disability and death and an important driver of health system utilization and spending. Continuity of care is a significant component of quality healthcare. However, an association between nurse-led services, interventions, patient outcomes and continuity of care at the primary and secondary interface as an outcome, has not been established for people with chronic disease. OBJECTIVE: To identify the effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface. DESIGN: Quantitative systematic review. DATA SOURCES: Systematic searches of Medline, Cochrane, Embase, Emcare, JBI and Scopus databases were conducted of studies published between 1946 and May 2019 using the search terms "nurse", "continuity of care" and "chronic disease". REVIEW METHODS: Quality of the included studies was assessed using the Cochrane risk of bias tool for randomized controlled trials and Joanna Briggs Institute quality appraisal checklists. A second reviewer screened 10% of full text articles and all articles in critical appraisal. Studies were excluded from the review if they were of poor methodological quality or the description of the effect of the nurse-led service was inadequately reported. RESULTS: Fourteen studies were included in the review (n=4,090 participants). All studies incorporated recognized continuity of care interventions. The nurse-led services were associated with fewer hospitalizations, reduced by 2-8.9% and re-admissions reduced by 14.8-51% (n=886). Reporting of positive patient experiences and improvement in symptoms and lifestyle was also evident. An association of nurse-led services with improved continuity of care between primary and secondary health services as an outcome per se could not be concluded. CONCLUSION: Nurse-led services for adults provide coordinated interventions that support continuity of care for people with chronic disease in both the primary and secondary healthcare settings that are associated with reduced hospitalizations or readmissions and patient satisfaction. However, the limited use of validated continuity of care outcome measurement tools precluded establishing correlations between interventions, patient outcomes and continuity of care as a specific outcome.

Microfluidic droplet application for bacterial surveillance in fresh-cut produce wash waters.

Foodborne contamination and associated illness in the United States is responsible for an estimated 48 million cases per year. Increased food demand, global commerce of perishable foods, and the growing threat of antibiotic resistance are driving factors elevating concern for food safety. Foodborne illness is often associated with fresh-cut, ready-to-eat produce commodities due to the perishable nature of the product and relatively minimal processing from farm to the consumer. The research presented here optimizes and evaluates the utility of microfluidic droplets, also termed ultra-miniaturized bioreactors, for rapid detection of viable Salmonella enterica ser. Typhimurium in a shredded lettuce wash water acquired from a major Mid-Atlantic produce processing facility (denoted as Producer) in the U.S. Using a fluorescently-labeled anti-S. Typhimurium antibody and relative fluorescence intensities, paired with in-droplet incubation, S. Typhimurium was detected and identified with 100% specificity in less than 5 h. In initial optimization experiments using S. Typhimurium-spiked sterile water, the relative fluorescence intensity of S. Typhimurium was approximately two times that of the observed relative intensities of five non-S. Typhimurium negative controls at 4-h incubation in droplets containing Rappaport-Vasiliadis (RV) broth at 37°C: relative fluorescence intensity for S. Typhimurium = 2.36 (95% CI: 2.15-2.58), Enterobacter aerogens 1.12 (95% CI: 1.09-1.16), Escherichia coli 700609 = 1.13 (95% CI: 1.09-1.17), E. coli 13706 1.13 (95% CI: 1.07-1.19), E. coli 700891 1.05 (95% CI: 1.03-1.07) and Citrobacter freundii 1.04 (95% CI: 1.03-1.05). S. Typhimurium- and E. aerogens-spiked shredded lettuce wash waters acquired from the Producer were then incubated 4 h in-droplet at 37°C with RV broth. The observed relative fluorescence of S. Typhimurium was significantly higher than that of E. aerogens, 1.56 (95% CI: 1.42-1.71) and 1.10 (95% CI: 1.08-1.12), respectively. While further optimization focusing on compatible concentration methodologies for highly-dilute produce water samples is needed, this application of droplet microfluidics shows great promise in dramatically shortening the time necessary-from days to hours-to confirm viable bacterial contamination in ready-to-eat produce wash waters used throughout the domestic and international food industry.

2-N-Arylthiazole inhibitors of Mycobacterium tuberculosis.

To develop agents for the treatment of infections caused by Mycobacterium tuberculosis, a novel phenotypic screen was undertaken that identified a series of 2-N-aryl thiazole-based inhibitors of intracellular Mycobacterium tuberculosis. Analogs were optimized to improve potency against an attenuated BSL2 H37Ra laboratory strain cultivated in human macrophage cells in vitro. The insertion of a carboxylic acid functionality resulted in compounds that retained potency and greatly improved microsomal stability. However, the strong potency trends we observed in the attenuated H37Ra strain were inconsistent with the potency observed for virulent strains in vitro and in vivo.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation.

BACKGROUND: The exact sequence of events leading to ultimate hepatocellular damage following ischemia/reperfusion (I/R) is incompletely understood. In this article, we review a mechanism of organ dysfunction after hepatic I/R or immunosuppressive treatment, in addition to the potential of liver sinusoidal endothelial cell (LSEC) protection and antiplatelet treatment for the suppression of hepatocellular damage. METHODS: A review of the literature, utilizing PubMed-NCBI, was used to provide information on the components necessary for the development of hepatocellular damage following I/R. RESULTS: It is well-established that LSECs damage following hepatic I/R or immunosuppressive treatment followed by extravasated platelet aggregation (EPA) is the root cause of organ dysfunction in liver transplantation. We have classified three phases, from LSECs damage to organ dysfunction, utilizing the predicted pathogenic mechanism of sinusoidal obstruction syndrome. The first phase is detachment of LSECs and sinusoidal wall destruction after LSECs injury by hepatic I/R or immunosuppressive treatment. The second phase is EPA, accomplished by sinusoidal wall destruction. The various growth factors, including thromboxane A2, serotonin, transforming growth factor-beta and plasminogen activator inhibitor-1, released by EPA in the Disse's space of zone three, induce portal hypertension and the progression of hepatic fibrosis. The third phase is organ dysfunction following portal hypertension, hepatic fibrosis, and suppressed liver regeneration through various growth factors secreted by EPA. CONCLUSION: We suggest that EPA in the space of Disse, initiated by LSECs damage due to hepatic I/R or immunosuppressive treatment, and activated platelets may primarily contribute to liver damage in liver transplantation. Endothelial protective therapy or antiplatelet treatment may be useful in the treatment of hepatic I/R following EPA.

Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases.

While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.

Mycobacterial nicotinate mononucleotide adenylyltransferase: structure, mechanism, and implications for drug discovery.

Nicotinate mononucleotide adenylyltransferase NadD is an essential enzyme in the biosynthesis of the NAD cofactor, which has been implicated as a target for developing new antimycobacterial therapies. Here we report the crystal structure of Mycobacterium tuberculosis NadD (MtNadD) at a resolution of 2.4 Å. A remarkable new feature of the MtNadD structure, compared with other members of this enzyme family, is a 310 helix that locks the active site in an over-closed conformation. As a result, MtNadD is rendered inactive as it is topologically incompatible with substrate binding and catalysis. Directed mutagenesis was also used to further dissect the structural elements that contribute to the interactions of the two MtNadD substrates, i.e. ATP and nicotinic acid mononucleotide (NaMN). For inhibitory profiling of partially active mutants and wild type MtNadD, we used a small molecule inhibitor of MtNadD with moderate affinity (Ki ∼ 25 µM) and antimycobacterial activity (MIC80) ∼ 40-80 µM). This analysis revealed interferences with some of the residues in the NaMN binding subsite consistent with the competitive inhibition observed for the NaMN substrate (but not ATP). A detailed steady-state kinetic analysis of MtNadD suggests that ATP must first bind to allow efficient NaMN binding and catalysis. This sequential mechanism is consistent with the requirement of transition to catalytically competent (open) conformation hypothesized from structural modeling. A possible physiological significance of this mechanism is to enable the down-regulation of NAD synthesis under ATP-limiting dormancy conditions. These findings point to a possible new strategy for designing inhibitors that lock the enzyme in the inactive over-closed conformation.

Increased allocation of adult-acquired carbohydrate to egg production results in its decreased allocation to sex pheromone production in mated females of the moth Heliothis virescens.

Females of most species of moths produce a volatile sex pheromone that attracts conspecific males over distance. In females of the polyandrous moth Heliothis virescens, feeding on carbohydrate (e.g. nectar) supplies precursor, via hemolymph trehalose, for both sex pheromone and egg production. With limited carbohydrate acquisition these two reproductive physiologies might compete for hemolymph trehalose, resulting in an allocation deficit to either sex pheromone or egg production. Using virgin and mated females, which have low and high egg maturation rates, respectively, we fed females a limited diet of (13)C-labeled glucose daily and, using mass isotopomer distribution analysis, determined allocations of adult-acquired carbohydrate (AAC) to newly synthesized pheromone and ovarian and egg fats, our proxies for allocation to egg production. With increased number of feeds, AAC enrichment of hemolymph trehalose increased, as expected. This led to mated females increasing their proportional allocation of AAC to ovarian and egg fats, but decreasing their proportional allocation of AAC to pheromone production. By contrast, virgins increased their proportional allocation of AAC to pheromone production with increased feeds, consistent with increasing AAC enrichment of hemolymph trehalose. These results show that with limited AAC intake, enhanced egg maturation in mated females results in reduced AAC allocation to pheromone production; this does not occur in virgins because of their lower egg maturation rate. This physiological competition for AAC corresponded with decreased pheromone production in mated moths to levels unlikely to attract mates. Therefore, the availability and/or allocation of AAC may be a proximate mechanism underlying the incidence of polyandry in this and other species of moths.

Combination of HIF-1α gene transfection and HIF-1-activated bone marrow-derived angiogenic cell infusion improves burn wound healing in aged mice.

Impaired burn wound healing in the elderly represents a major clinical problem. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that orchestrates the cellular response to hypoxia. Its actions in dermal wounds promote angiogenesis and improve healing. In a murine burn wound model, aged mice had impaired wound healing associated with reduced levels of HIF-1. When gene therapy with HIF-1 alone did not correct these deficits, we explored the potential benefit of HIF-1 gene therapy combined with the intravenous infusion of bone marrow-derived angiogenic cells (BMDACs) cultured with dimethyloxalylglycine (DMOG). DMOG is known to reduce oxidative degradation of HIF-1. The mice treated with a plasmid DNA construct expressing a stabilized mutant form of HIF-1α (CA5-HIF-1α)+BMDACs had more rapid wound closure. By day 17, there were more mice with completely closed wounds in the treated group (χ(2), P=0.05). The dermal blood flow measured by laser Doppler showed significantly increased wound perfusion on day 11. Homing of BMDACs to the burn wound was dramatically enhanced by CA5-HIF-1α gene therapy. HIF-1α mRNA expression in the burn wound was increased after transfection with CA5-HIF-1α plasmid. Our findings offer insight into the pathophysiology of burns in the elderly and point to potential targets for developing new therapeutic strategies.

Effect of envelope material on biosecurity during emergency bovine mortality composting.

The biosecurity of composting as an emergency disposal method for cattle mortalities caused by disease was evaluated by conducting full-scale field trials begun during three different seasons and using three different envelope materials. Process biosecurity was significantly affected by the envelope material used to construct the composting matrix. Internal temperatures met USEPA Class A time/temperature criteria for pathogen reduction in 89%, 67%, and 22%, respectively of seasonal test units constructed with corn silage, straw/manure, or ground cornstalks. In trials begun in the winter, survival times of vaccine strains of avian encephalomyelitis and Newcastle disease virus were noticeably shorter in silage test units than in the other two materials, but during summer/spring trials survival times in ground cornstalk and straw/manure test units were similar to those in test units constructed with silage.

Reverse line blot probe design and polymerase chain reaction optimization for bloodmeal analysis of ticks from the eastern United States.

Determining the host preference of vector ticks is vital to elucidating the eco-epidemiology of the diseases they spread. Detachment of ticks from captured hosts can provide evidence of feeding on those host species, but only for those species that are feasible to capture. Recently developed, highly sensitive molecular assays show great promise in allowing host selection to be determined from minute traces of host DNA that persist in recently molted ticks. Using methods developed in Europe as a starting-point, we designed 12S rDNA mitochondrial gene probes suitable for use in a reverse line blot (RLB) assay of ticks feeding on common host species in the eastern United States. This is the first study to use the 12S mitochondrial gene in a RLB bloodmeal assay in North America. The assay combines conventional PCR with a biotin-labeled primer and reverse line blots that can be stripped and rehybridized up to 20 times, making the method less expensive and more straightforward to interpret than previous methods of tick bloodmeal identification. Probes were designed that target the species, genus, genus group, family, order, or class of eight reptile, 13 birds, and 32 mammal hosts. After optimization, the RLB assay correctly identified the current hostspecies for 99% of ticks [Amblyomma americanum (L.) and eight other ixodid tick species] collected directly from known hosts. The method identified previous-host DNA for approximately half of all questing ticks assayed. Multiple bloodmeal determinations were obtained in some instances from feeding and questing ticks; this pattern is consistent with previous RLB studies but requires further investigation. Development of this probe library, suitable for eastern U.S. ecosystems, opens new avenues for eco-epidemiological investigations of this region's tick-host systems.

Intensity-modulated and image-guided radiation therapy for treatment of genitourinary carcinomas in dogs.

BACKGROUND: External beam radiation therapy can be used to treat pelvic tumors in dogs, but its utility is limited by lack of efficacy data and associated late complications. HYPOTHESIS/OBJECTIVES: The objective of this study was to assess local tumor control, overall survival, and toxicosis after intensity-modulated and image-guided radiation therapy (IM/IGRT) for treatment of genitourinary carcinomas (CGUC) in dogs. ANIMALS: 21 client-owned dogs. METHODS: A retrospective study was performed. Medical records of dogs for which there was intent to treat with a course of definitive-intent IM/IGRT for CGUC between 2008 and 2011 were reviewed. Descriptive and actuarial statistics comprised the data analysis. RESULTS: Primary tumors were located in the prostate (10), urinary bladder (9), or urethra (2). The total radiation dose ranged from 54-58 Gy, delivered in 20 daily fractions. Grade 1 and 2 acute gastrointestinal toxicoses developed in 33 and 5% of dogs, respectively. Grade 1 and 2 acute genitourinary and grade 1 acute integumentary toxicoses were documented in 5, 5, and 20% of dogs, respectively. Four dogs experienced late grade 3 gastrointestinal or genitourinary toxicosis. The subjective response rate was 60%. The median event-free survival was 317 days; the overall median survival time was 654 days. Neither local tumor control nor overall survival was statistically dependent upon location of the primary tumor. CONCLUSIONS AND CLINICAL IMPORTANCE: IM/IGRT is generally well-tolerated and provides an effective option for locoregional control of CGUC. As compared with previous reports in the veterinary literature, inclusion of IM/IGRT in multimodal treatment protocols for CGUC can result in superior survival times; controlled prospective evaluation is warranted.

Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes.

The seemingly inexorable decline in insulin independence after islet transplant alone (ITA) has raised concern about its clinical utility. We hypothesized that induction immunosuppression therapy determines durability of insulin independence. We analyzed the proportion of insulin-independent patients following final islet infusion in four groups of ITA recipients according to induction immunotherapy: University of Minnesota recipients given FcR nonbinding anti-CD3 antibody alone or T cell depleting antibodies (TCDAb) and TNF-α inhibition (TNF-α-i) (group 1; n = 29); recipients reported to the Collaborative Islet Transplant Registry (CITR) given TCDAb+TNF-α-i (group 2; n = 20); CITR recipients given TCDAb without TNF-α-i (group 3; n = 43); and CITR recipients given IL-2 receptor antibodies (IL-2RAb) alone (group 4; n = 177). Results were compared with outcomes in pancreas transplant alone (PTA) recipients reported to the Scientific Registry of Transplant Recipients (group 5; n = 677). The 5-year insulin independence rates in group 1 (50%) and group 2 (50%) were comparable to outcomes in PTA (group 5: 52%; p>>0.05) but significantly higher than in group 3 (0%; p = 0.001) and group 4 (20%; p = 0.02). Induction immunosuppression was significantly associated with 5-year insulin independence (p = 0.03), regardless of maintenance immunosuppression or other factors. These findings support potential for long-term insulin independence after ITA using potent induction therapy, with anti-CD3 Ab or TCDAb+TNF-α-i.

Energy use in pig production: an examination of current Iowa systems.

This paper compares energy use for different pig production systems in Iowa, a leader in US swine production. Pig production systems include not only the growth and performance of the pigs, but also the supporting infrastructure of pig production. This supporting infrastructure includes swine housing, facility management, feedstuff provision, swine diets, and manure management. Six different facility type × diet formulation × cropping sequence scenarios were modeled and compared. The baseline system examined produces 15,600 pigs annually using confinement facilities and a corn-soybean cropping sequence. Diet formulations for the baseline system were corn-soybean meal diets that included the synthetic AA l-lysine and exogenous phytase. The baseline system represents the majority of current US pork production in the Upper Midwest, where most US swine are produced. This system was found to require 744.6 MJ per 136-kg market pig. An alternative system that uses bedded hoop barns for grow-finish pigs and gestating sows would require 3% less (720.8 MJ) energy per 136-kg market pig. When swine production systems were assessed, diet type and feed ingredient processing were the major influences on energy use, accounting for 61 and 79% of total energy in conventional and hoop barn-based systems, respectively. Improving feed efficiency and better matching the diet formulation with the thermal environment and genetic potential are thus key aspects of reducing energy use by pig production, particularly in a hoop barn-based system. The most energy-intensive aspect of provisioning pig feed is the production of synthetic N for crop production; thus, effectively recycling manure nutrients to cropland is another important avenue for future research. Almost 25% of energy use by a conventional farrow-to-finish pig production system is attributable to operation of the swine buildings. Developing strategies to minimize energy use for heating and ventilation of swine buildings while maintaining pig comfort and performance is a third critical area for future research. The hoop barn-based alternative uses 64% less energy to operate buildings but requires bedding and 2.4% more feed. Current Iowa pig production systems use energy differently but result in similar total energy use. Compared with 1975, current farrow-to-finish systems in Iowa require 80% less energy to produce live market pigs.

Factors contributing to the poor performance of a soybean aphid parasitoid Binodoxys communis (Hymenoptera: Braconidae) on an herbivore resistant soybean cultivar.

Host plant resistance and biological control are important components of integrated pest management programs. However, plants expressing resistance to herbivores may also have direct or indirect negative effects on natural enemies simultaneously providing pest suppression. Soybean aphids (Aphis glycines Matsumura) are invasive and serious pests of soybean (Glycine max L.) in the United States. Several soybean lines with aphid resistance have been identified, but the long-term impact of these resistant plants on soybean aphid biological control agents is uncertain. In a previous study, we reported that a soybean aphid parasitoid, Binodoxys communis (Gahan) had lower mummy production on resistant plants compared with a near isogenic susceptible soybean line, but the reason for this was unclear. Therefore, we examined three possible mechanisms to explain these findings: 1) resistant plants directly impact wasp emergence and longevity, 2) varying aphid density influences parasitism rates, and 3) resistant plants indirectly affect wasp development through reduced aphid longevity. We found that parasitoids in this study were not directly influenced by resistant cultivars, as there was no difference in wasp adult emergence or longevity between resistant and susceptible plants. There was also no significant effect of aphid density on mummy production over the range of aphid densities we tested. However, aphids on resistant plants had significantly shorter lifespans and were unable to survive long enough to develop into mummies compared with aphids on susceptible plants. We discuss these results and possible implications for integrating biological control and host plant resistance within soybean aphid integrated pest management programs.

Current Insights into the role of HIF-1 in cutaneous wound healing.

Hypoxia Inducible Factor-1 (HIF-1) is considered the major coordinator of the cellular adaptive response to hypoxia. Over recent years, its activity in the context of wound healing has been the object of increasing investigation. On the molecular level, HIF-1 transcriptional target products have been shown to regulate the process of endothelial cell survival, migration and proliferation (VEGF, ANGPT-1, ANGPT-2, ANGPT-4, FGF-2, PlGF, PDGF-B, RGC-32), vascular smooth muscle cell migration and proliferation (FGF-2, EGF, PDGF, thrombospondin) and mobilization of Circulating Angiogenic Cells to the periphery (SFD-1/CXCR4). Studies on the effect of HIF-1 on the expression and activity of extracellular cell matrix modifying enzymes, such as MMPs and prolidase, have been conducted in the context of tumor angiogenesis and metastasis, and have resulted in controversial findings. A growing body of evidence suggests that HIF-1 also affects reepithelialization of the wound bed, through increasing keratinocyte migration, but decreasing their proliferation. Diminished HIF-1 levels and activity have been documented in conditions of impaired wound healing, such as wound healing in aged and in diabetic mice. The increasing number of studies on the role of HIF-1 in wound healing, apart from answering certain questions, has also raised an equal number, if not more. Clarifying the topics that still remain unclear could introduce a new era of HIF-1 targeted management of a wide range of problematic wounds.

Comparison of steer behavior when housed in a deep-bedded hoop barn versus an open feedlot with shelter.

The use of hoop barns as an alternative housing system for beef cattle has not been widely researched. The objectives of this study were to determine the main effects of behavior of steers 1) over winter and summer, 2) when housed in either a hoop barn or a conventional feedlot, and 3) interactions between season and housing system. A total of 960 crossbred Bos taurus steers were used [August 2006 to April 2008 (2 winter and 2 summer trials)]. Steers were housed in either 1 deep-bedded hoop barn (n = 12 pens; 4.65 m(2)/steer) or 1 open feedlot with shelter (n = 12 pens; 14.7 m(2)/steer). Steers were ear tagged, implanted, and weighed (414 ± 36 kg) on arrival and allotted to treatments that were balanced for source, BW, and hide color. Behavioral data (3 postures and 2 behaviors) were collected using a 10-min live scan. The experimental unit for behavior was a pen of steers. Behavioral data were arcsine transformed to achieve a normal distribution. There were no (P > 0.05) differences for time spent at bunk or waterer for steers between housing treatments. Steers housed in an open feedlot with shelter spent less time lying and more time standing and walking (P < 0.05) compared with steers housed in a hoop barn. There were no (P = 0.32) differences between seasons for standing. Steers spent more time at the bunk (P < 0.0001) and waterer (P < 0.0001) in the summer compared with the winter. In the winter, steers engaged in more lying (P = 0.0002) and walking (P < 0.0001). Overall, steers stood less (P = 0.006) and spent more time lying (P = 0.024) when housed in a hoop barn than in the open feedlot with shelter regardless of season. Steers housed in the open feedlot with shelter walked more (P < 0.0001) than steers housed in the hoop barn and walked more (P < 0.0001) in winter than in summer months (6 vs. 3%). There were no (P > 0.05) differences in time spent at bunk and waterer between housing systems within season, but time spent at the waterer and bunk decreased (P < 0.05) for both housing systems during the winter. In conclusion, housing 40 steers per pen in a cornstalk-bedded hoop barn at 4.65 m(2)/steer does not result in adverse behavioral alterations and can be considered as a housing alternative for finishing steers in the Midwestern United States when compared with steers fed in an open feedlot with shelter provided.

MicroRNA-192 and -215 are upregulated in human gastric cancer in vivo and suppress ALCAM expression in vitro.

The dismal outcome of gastric cancer patients highlights the need for diagnostic biomarkers and effective therapeutic targets, such as microRNAs. We sought to discover microRNAs involved in gastric cancer, and to elucidate their downstream target mechanisms. Both cultured gastric epithelial cells (HFE145 and NCI-N87) and primary human gastric tissues (31 non-neoplastic stomach (NS) and 25 gastric carcinomas (GC)) were studied. MicroRNA microarrays and quantitative RT-PCR were applied to discover and verify differentially expressed microRNAs. in vitro cell migration and invasion, cell proliferation, cell cycle and apoptosis assays were executed to elucidate biological effects of microRNA-192 and -215. Western blotting and luciferase assays were performed to confirm direct messenger RNA targeting by microRNA-192 and -215. MicroRNA microarray analyses revealed that 25 and 20 microRNAs were upregulated and downregulated in GC vs NS, respectively. Expression levels of both microRNA-192 and -215 were significantly higher in GC than in NS (P<0.05). Luciferase assays suggested that microRNA-215 inhibits activated leukocyte cell adhesion molecule (ALCAM) expression at the posttranscriptional level. In addition, expression levels of ALCAM were significantly lower in GC than in NS. Mimics and inhibitors, respectively, of microRNA-192 or -215 exerted no effect on cell cycle or apoptosis in the immortalized normal gastric cell line HFE145 or the gastric cancer cell line NCI-N87. However, mimics of microRNA-192 or -215 significantly increased growth rates in HFE145 cells, whereas inhibitors of microRNA-192 or -215 caused significant decreases in growth rates in NCI-N87 cells. ALCAM knockdown by an ALCAM-specific siRNA significantly increased cell growth in HFE145 cells. Both transfection of mimics of microRNA-192 or -215 and ALCAM knockdown by an ALCAM-specific siRNA significantly increased the migration of HFE145 cells. In conclusion, in gastric cancer, both microRNA-192 and -215 are overexpressed in vivo and exert cell growth and migration-promoting effects in vitro, thus representing potential microRNAs with a role in cancer in the human stomach.