Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. DCs have been shown to possess a high plasticity showing different phenotypes in response to their microenvironment. For example, tumor-associated DCs can acquire an angiogenic phenotype thus promoting tumor growth. Further, DCs cultured in vitro under different conditions are able to upregulate the expression of endothelial markers and to express angiogenic factors. Indeed, it has been shown that soluble factors such as VEGF of PGE-2, that are present in the microenvironment of several tumors, affect the biology of these cells. We hypothesize that in addition to soluble factors the adhesion to different substrates will also define the phenotype and function of DCs. Herewith we demonstrate that murine myeloid(m) DCs upregulate endothelial markers such as VE-Cadherin, and to a lesser extent TIE-2, and decrease their immune capabilities when cultured on solid surfaces as compared with the same cells cultured on ultra-low binding (ULB) surfaces. On the other hand, the expression of angiogenic molecules at the level of RNA was not different among these cultures. In order to further investigate this phenomenon we used the murine ID8 model of ovarian cancer which can generate solid tumors when cancer cells are injected subcutaneously or a malignant ascites when they are injected intraperitoneally. This model gave us the unique opportunity to investigate DCs in suspension or attached to solid surfaces under the influence of the same tumor cells. We were able to determine that DCs present in solid tumors showed higher levels of expression of endothelial markers and angiogenic molecules but were not able to respond to inflammatory stimuli at the same extent as DCs recovered from ascites. Moreover, mDCs cultured on ULB surfaces in the presence of tumor factors do not expressed endothelial markers. Taking into account all these data we consider that tumor factors might be responsible for inducing angiogenic properties in DCs, but that in some settings the expression of endothelial markers such as VE-Cadherin and TIE-2 might be a function of attachment to solid surfaces and independent of the angiogenic properties of these cells.

BACKGROUND: Following gastric bypass surgery (GBP), there is a post-prandial rise of incretin and satiety gut peptides. The mechanisms of enhanced incretin release in response to nutrients after GBP is not elucidated and may be in relation to altered nutrient transit time and/or malabsorption. METHODS: Seven morbidly obese subjects (BMI = 44.5 ± 2.8 kg/m(2)) were studied before and 1 year after GBP with a D:-xylose test. After ingestion of 25 g of D:-xylose in 200 mL of non-carbonated water, blood samples were collected at frequent time intervals to determine gastric emptying (time to appearance of D:-xylose) and carbohydrate absorption using standard criteria. RESULTS: One year after GBP, subjects lost 45.0 ± 9.7 kg and had a BMI of 27.1 ± 4.7 kg/m(2). Gastric emptying was more rapid after GBP. The mean time to appearance of D:-xylose in serum decreased from 18.6 ± 6.9 min prior to GBP to 7.9 ± 2.7 min after GBP (p = 0.006). There was no significant difference in absorption before (serum D:-xylose concentrations = 35.6 ± 12.6 mg/dL at 60 min and 33.9 ± 9.1 mg/dL at 180 min) or 1 year after GBP (serum D:-xylose = 31.5 ± 18.1 mg/dL at 60 min and 27.2 ± 11.9 mg/dL at 180 min). CONCLUSIONS: These data confirm the acceleration of gastric emptying for liquid and the absence of carbohydrate malabsorption 1 year after GBP. Rapid gastric emptying may play a role in incretin response after GBP and the resulting improved glucose homeostasis.

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell-(DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.

We demonstrate two techniques to improve the quality of reconstructed optical projection tomography (OPT) images using the modulation transfer function (MTF) as a function of defocus experimentally determined from tilted knife-edge measurements. The first employs a 2-D binary filter based on the MTF frequency cut-off as an additional filter during back-projection reconstruction that restricts the high frequency information to the region around the focal plane and progressively decreases the spatial frequency bandwidth with defocus. This helps to suppress "streak" artifacts in OPT data acquired at reduced angular sampling, thereby facilitating faster OPT acquisitions. This method is shown to reduce the average background by approximately 72% for an NA of 0.09 and by approximately 38% for an NA of 0.07 compared to standard filtered back-projection. As a biological illustration, a Fli:GFP transgenic zebrafish embryo (3 days post-fertilisation) was imaged to demonstrate the improved imaging speed (a quarter of the acquisition time). The second method uses the MTF to produce an appropriate deconvolution filter that can be used to correct for the spatial frequency modulation applied by the imaging system.

PURPOSE:  Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management.  DESIGN AND METHODS:  We report on a randomized controlled trial examining the impact of a multifaceted telehealth intervention on health, mental health, and service utilization outcomes among homebound medically ill older adults diagnosed with HF or COPD. Random effects regression modeling was used, and we hypothesized that older adults in the telehealth intervention (n = 51) would receive significantly better quality of care resulting in improved scores in health-related quality of life, mental health, and satisfaction with care at 3 months follow-up as compared with controls (n = 51) and service utilization outcomes at 12 months follow-up.  RESULTS:  At follow-up, the telehealth intervention group reported greater increases in general health and social functioning, and improved in depression symptom scores as compared with usual care plus education group. The control group had significantly more visits to the emergency department than the telehealth group. There was an observed trend toward fewer hospital days for telehealth participants, but it did not reach significance at 12 months.  IMPLICATIONS:  Telehealth may be an efficient and effective method of systematically delivering integrated care in the home health sector. The use of telehealth technology may benefit homebound older adults who have difficulty accessing care due to disability, transportation, or isolation.

RATIONALE: Regulator of G-protein signaling 4 (RGS4) is a brain-enriched negative modulator of G-protein-coupled receptor signaling. Decreased availability of RGS4 in the frontal cortex and striatum has been described in animal models of schizophrenia and drug addiction. However, cellular and behavioral consequences of dysregulated RGS4-dependent receptor signaling in the brain remain poorly understood. OBJECTIVE: This study aims to investigate whether RGS4, through inhibiting the function of mGluR5 receptors in the dorsal striatum (dSTR), regulates cellular and behavioral responses to acute amphetamine. METHODS: After herpes simplex virus-RGS4 was infused into the dSTR, RGS4 overexpression as well as binding of recombinant RGS4 to mGluR5 was assessed. The effect of RGS4 overexpression on behavioral activity induced by the intrastriatal mGluR5 agonist, DHPG, or amphetamine was recorded. Activation of extracellular signal-regulated kinase (ERK) and Akt (protein kinase B) was measured in the dSTR tissue at the end of each behavioral experiment. RESULTS: RGS4 overexpressed in the dSTR coimmunoprecipitated with mGluR5 receptors and suppressed both behavioral activity and phospho-ERK levels induced by DHPG. RGS4 overexpression or the mGluR5 antagonist, 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP), attenuated amphetamine-induced phospho-ERK (but not phospho-Akt) levels. RGS4 suppressed amphetamine-induced vertical activity and augmented horizontal activity over 90 min. Similarly, MTEP augmented amphetamine-induced horizontal activity, but did not affect vertical activity. CONCLUSIONS: The present data demonstrate that RGS4 in the dSTR attenuates amphetamine-induced ERK signaling and decreases the behavioral efficacy of acute amphetamine likely by limiting mGluR5 function.

We describe a new light transport model, which was applied to three-dimensional lifetime imaging of Förster resonance energy transfer in mice in vivo. The model is an approximation to the radiative transfer equation and combines light diffusion and ray optics. This approximation is well adopted to wide-field time-gated intensity-based data acquisition. Reconstructed image data are presented and compared with results obtained by using the telegraph equation approximation. The new approach provides improved recovery of absorption and scattering parameters while returning similar values for the fluorescence parameters.

Objective: To describe the potential long-term malnutrition risk after Roux-en-Y Gastric Bypass (GBP) through an uncommon occurrence of inflammatory bowel disease (IBD) after GBP which posed a serious threat to the nutritional status and life of the patient.Methods: The patient is a 44-year-old woman who developed Crohn's disease 4 years after GBP. The double insult of IBD and GBP resulted in severe malnutrition with an albumin of 0.9 g/dl (3.5-5 g/dL), weight loss, and watery diarrhea with 6 hospital admissions in 7 months.Results: The administration of total parenteral nutrition (TPN) with aggressive macronutrient, vitamin, and mineral repletion resulted in marked improvement in the patient's strength, function, and quality of life, in parallel with improvement in the IBD symptoms.Conclusion: Rarely, IBD develops following GBP but the relationship between the two conditions remains unclear. Regardless, adding to the altered anatomy after bariatric surgery, the further insult of IBD poses a severe threat to the nutritional status of these patients. Malnutrition needs to be recognized and aggressively treated. Nutritional markers should be followed closely in this population to avert onset of severe malnutrition.

Chronic methamphetamine (meth) can lead to persisting cognitive deficits in human addicts and animal models of meth addiction. Here, we examined the impact of either contingent or non-contingent meth on memory performance using an object-in-place (OIP) task, which measures the ability to detect an object relative to its location and surrounding objects. Further, we quantified monoamine transporter levels and markers of neurotoxicity within the OIP circuitry and striatum. Male Long-Evans rats received an acute meth binge (4 × 4 mg/kg i.p., 2 h intervals) or self-administered meth (0.02 mg/infusion, i.v.; 7 days for 1 h/day, followed by 14 days for 6 h/day).Rats were tested for OIP recognition memory following one week of withdrawal. Subsequently, transporters for serotonin (SERT) and norepinephrine (NET) were quantified using Western blot in tissue obtained from the hippocampus, perirhinal cortex, and prefrontal cortex. In addition, striatal dopamine transporters, tyrosine hydroxylase, and glial fibrillary acidic protein were measured to assess potential neurotoxicity. Control (saline-treated) rats spent more time interacting with the objects in the changed locations. In contrast, contingent or non-contingent meth resulted in disrupted OIP performance as seen by similar amounts of time spent with all objects, regardless of location. While only acute meth binge produced signs of neurotoxicity, both meth regimens decreased SERT in the perirhinal cortex and hippocampus. Only meth self-administration resulted in a selective decrease in NET. Meth-induced changes in SERT function in the OIP circuitry may underlie memory deficits independently of overt neurotoxic effects.