Microglia are the brain's tissue macrophage and representative of the innate immune system. These cells normally provide tissue maintenance and immune surveillance of the brain. In the Alzheimer's disease brain amyloid deposition provokes the phenotypic activation of microglia and their elaboration of proinflammatory molecules. Recent work has implicated Toll-like receptors in microglial recognition and response to amyloid fibrils. It is now evident that these cells exhibit more complex and heterogeneous phenotypes than previously appreciated that reflect both the plasticity of cells in this lineage and their ability to transition between activation states. The phenotypic diversity is associated with inactivation of the inflammatory response and tissue repair. We discuss recent evidence that the brain can be infiltrated by circulating monocytes in the diseased brain and that these cells may comprise a unique subpopulation of myeloid cells that may be functionally distinct from the endogenous microglia.

We present both experimental measurements and Monte-Carlo-based simulations of the diffusely backscattered intensity patterns that arise from illuminating a turbid medium with a polarized laser beam. It is rigorously shown that, because of axial symmetry of the system, only seven elements of the effective backscattering Mueller matrix are independent. A new numerical method that allows simultaneous calculation of all 16 elements of the two-dimensional Mueller matrix is used. To validate our method we compared calculations to measurements from a turbid medium that consisted of polystyrene spheres of different sizes and concentrations in deionized water. The experimental and numerical results are in excellent agreement.

Real-time prediction of glucose via the proposed NNM may provide a means of intelligent therapeutic guidance and direction.

A wearable sweat biosensing device is demonstrated that stimulates sweat and continuously measures sweat ethanol concentrations at 25 s intervals, which is then correlated with blood ethanol during a >3 hour testing phase.

Abbreviations: (AD%) absolute difference percent, (ANN) artificial neural network, (CGM) continuous glucose monitoring, (CGMS) continuous clucose monitoring system, (GUI) graphical user interface, (MAD%) mean absolute difference percent Keywords: neural network, diabetes, glycemic predictions, CGM

A polarimetric glucose sensor utilizing a digital closed-loop controller was designed and implemented during this study. Its potential as a noninvasive glucose sensor was evaluated in vitro for both glucose-doped water and bovine aqueous humor mediums. A physiological hyperglycemic concentration range was used in both calibration and validation of each set of experiments. Ideally, the end application of this system could estimate blood glucose concentrations indirectly by measuring the amount of rotation of a light beam's polarization state after it propagates through the aqueous humor contained within the anterior chamber of the eye. The polarimeter designed in this study differs from similar investigated systems in that it utilizes a digital closed-loop control system. This type of controller was implemented in order to further improve system repeatability and stability without sacrificing accuracy. Unique to this investigation, independent validation sets other than those used to create each respective calibration model were obtained. The results of the glucose-doped water experiments yielded mean standard errors of prediction for calibration and validation of 6.91 and 8.84 mg/dl, respectively. The mean standard errors of prediction during calibration and validation of the glucose-doped aqueous humor experiments were higher at 27.20 and 27.47 mg/dl, respectively, due to medium degradation over time while exposed to air.

The high fatality rate associated with the late detection of skin cancer makes early detection crucial in preventing death. The current method for determining if a skin lesion is suspect to cancer is initially based on the patient's and physician's subjective observation of the skin lesion. Physicians use a set of parameters called the ABCD (asymmetry, border, color, diameter) rule to help facilitate diagnosis of potential cancerous lesions. Lesions that are suspicious then require a biopsy, which is a painful, invasive, and a time-consuming procedure. In an attempt to reduce the aforementioned undesirable elements currently associated with skin cancer diagnosis, a novel optical polarization-imaging system is described that has the potential to noninvasively detect cancerous lesions. The described system generates the full 16-element Mueller matrix in less than 70 s. The operation of the system was tested in transmission, specular reflection, and diffuse reflectance modes, using known samples, such as a horizontal linear polarizer, a mirror, and a diffuser plate. In addition, it was also used to image a benign lesion on a human subject. The results of the known samples are in good agreement with their theoretical values with an average accuracy of 97.96% and a standard deviation of 0.0084, using 16 polarization images. The system accuracy was further increased to 99.44% with a standard deviation of 0.005, when 36 images were used to generate the Mueller matrix.

Background Prostate cancer is poorly responsive to immune checkpoint inhibition, yet a combination with radiotherapy may enhance the immune response. In this study, we combined radiotherapy with immune checkpoint inhibition (iRT) in a castration-resistant prostate cancer (CRPC) preclinical model. Methods Two Myc-CaP tumor grafts were established in each castrated FVB mouse. Anti-PD-1 or anti-PD-L1 antibodies were given and one graft was irradiated 20 Gy in 2 fractions. Results In CRPC, a significant increase in survival was found for radiation treatment combined with either anti-PD-1 or anti-PD-L1 compared to monotherapy. The median survival for anti-PD-L1 alone was 13 days compared to 30 days for iRT ( p = 0.0003), and for anti-PD-1 alone was 21 days compared to 36 days for iRT ( p = 0.0009). Additional treatment with anti-CD8 antibody blocked the survival effect. An abscopal treatment effect was observed for iRT in which the unirradiated graft responded similarly to the irradiated graft in the same mouse. At 21 days, the mean graft volume for anti-PD-1 alone was 2094 mm 3 compared to iRT irradiated grafts 726 mm 3 ( p = 0.04) and unirradiated grafts 343 mm 3 ( p = 0.0066). At 17 days, the mean graft volume for anti-PD-L1 alone was 1754 mm 3 compared to iRT irradiated grafts 284 mm 3 ( p = 0.04) and unirradiated grafts 556 mm 3 ( p = 0.21). Flow cytometry and immunohistochemistry identified CD8+ immune cell populations altered by combination treatment in grafts harvested at the peak effect of immunotherapy, 2–3 weeks after starting treatment. Conclusions These data provide preclinical evidence for the use of iRT targeting PD-1 and PD-L1 in the treatment of CRPC. Immune checkpoint inhibition combined with radiotherapy treats CPRC with significant increases in median survival compared to drug alone: 70% longer for anti-PD-1 and 130% for anti-PD-L1, and with an abscopal treatment effect. Precis Castration-resistant prostate cancer in a wild-type mouse model is successfully treated by X-ray radiotherapy combined with PD-1 or PD-L1 immune checkpoint inhibition, demonstrating significantly increased median overall survival and robust local and abscopal treatment responses, in part mediated by CD8 T-cells. Electronic supplementary material The online version of this article (10.1186/s40425-019-0704-z) contains supplementary material, which is available to authorized users.