Neuroinflammation, Microglia and Implications for Anti-Inflammatory Treatment in Alzheimer's Disease

Neuroinflammation has been implicated in the pathology of Alzheimer's disease (AD) for decades. Still it has not been fully understood when and how inflammation arises in the course of AD. Whether inflammation is an underling cause or a resulting condition in AD remains unresolved. Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative diseases. However, also beneficial aspects of microglial activation have been identified. The purpose of this review is to highlight new insights into the detrimental and beneficial role of neuroinflammation in AD. It is our intention to focus on newer controversies in the field of microglia activation. Precisely, we want to shed light on whether neuroinflammation is associated to brain tissue damage and functional impairment or is there also a damage limiting activity. In regard to this, we discuss the limitations and the advantages of anti-inflammatory treatment options and identify what future implications might result from this underling neuroinflammation for AD therapy

Differential regulation of myeloid leukemias by the bone marrow microenvironment

Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow microenvironment (BMM)1, and may be the cause of relapse following chemotherapy.2 Targeting the niche is a novel strategy to eliminate persistent and drug-resistant LSC. CD443,4 and IL-65 have been implicated previously in the LSC niche. Transforming growth factor (TGF)-β1 is released during bone remodeling6 and plays a role in maintenance of CML LSCs7, but a role for TGF-β1 from the BMM has not been defined. Here, we show that alteration of the BMM by osteoblastic cell-specific activation of the parathyroid hormone (PTH) receptor8,9 attenuates BCR-ABL1-induced CML-like myeloproliferative neoplasia (MPN)10 but enhances MLL-AF9-induced AML11 in mouse transplantation models, possibly through opposing effects of increased TGF-β1 on the respective LSC. PTH treatment caused a 15-fold decrease in LSCs in wildtype mice with CML-like MPN, and reduced engraftment of immune deficient mice with primary human CML cells. These results demonstrate that LSC niches in chronic and acute myeloid leukemias are distinct, and suggest that modulation of the BMM by PTH may be a feasible strategy to reduce LSC, a prerequisite for the cure of CML

Star Formation Rates in Resolved Galaxies: Calibrations with Near- and Far-infrared Data for NGC 5055 and NGC 6946

We use the near-infrared Brγ hydrogen recombination line as a reference star formation rate (SFR) indicator to test the validity and establish the calibration of the Herschel/PACS 70 μm emission as a SFR tracer for sub-galactic regions in external galaxies. Brγ offers the double advantage of directly tracing ionizing photons and of being relatively insensitive to the effects of dust attenuation. For our first experiment, we use archival Canada-France-Hawaii Telescope Brγ and Ks images of two nearby galaxies: NGC 5055 and NGC 6946, which are also part of the Herschel program KINGFISH (Key Insights on Nearby Galaxies: a Far-Infrared Survey with Herschel). We use the extinction corrected Brγ emission to derive the SFR(70) calibration for H II regions in these two galaxies. A comparison of the SFR(70) calibrations at different spatial scales, from 200 pc to the size of the whole galaxy, reveals that about 50% of the total 70 μm emission is due to dust heated by stellar populations that are unrelated to the current star formation. We use a simple model to qualitatively relate the increase of the SFR(70) calibration coefficient with decreasing region size to the star formation timescale. We provide a calibration for an unbiased SFR indicator that combines the observed Hα with the 70 μm emission, also for use in H II regions. We briefly analyze the PACS 100 and 160 μm maps and find that longer wavelengths are not as good SFR indicators as 70 μm, in agreement with previous results. We find that the calibrations show about 50% difference between the two galaxies, possibly due to effects of inclination

Musculoskeletal injuries among operating room nurses: results from a multicenter survey in Rome, Italy

Aim: Chronic disorders of the musculoskeletal system, particularly low back pain (LBP), are increasing and represent a social and economic problem of growing importance, especially if correlated with working conditions. Health care workers are at higher risk of developing LBP during work shifts in the hospital. The aim of this study was to assess the prevalence of LBP among operating room nurses and to investigate the risk factors for musculoskeletal injuries in the operating room. Methods: We carried out a cross-sectional study that included operating room nurses from nine hospitals. Information on sociodemographic characteristics, lifestyle habits, working activity and psychological attitude of nurses was collected using an anonymous self-administered structured questionnaire. We evaluated the association of frequency, localization and intensity of LBP (FLI) with qualitative variables, making use of univariate analysis, chi-square test and Fisher's exact test. Multiple logistic regression analysis was performed to identify the variables that affected the FLI. The covariates included in the model were the variables that had a p 35 years vs. age <35 (OR = 2.68; 95% CI = 1.17–6.18) and diurnal work shift vs. diurnal/ nocturnal (OR = 4.00; 95% CI = 1.72–9.0) represent risk factors associated with FLI, while physical activity is a protective factor (OR = 0.47; 95% CI = 0.20–1.08). Conclusion: The data suggest that it is important to promote new programs of prevention based on professional training and physical activity among nurses and to improve the organization of work shifts in the hospital

Altered monocyte activation markers in Tourette's syndrome: a case-control study

Background: Infections and immunological processes are likely to be involved in the pathogenesis of Tourette's syndrome (TS). To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. Methods: In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble CD14 (sCD14), IL1-receptor antagonist (IL1-ra), and serum neopterin were detected by immunoassays. Results: We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. Conclusions: The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions

Is the PANSS used correctly? a systematic review

<p>Abstract</p> <p>Background</p> <p>The PANSS (Positive and Negative Syndrome Scale) is one of the most important rating instruments for patients with schizophrenia. Nevertheless, there is a long and ongoing debate in the psychiatric community regarding its mathematical properties.</p> <p>All 30 items range from 1 to 7 leading to a minimum total score of 30, implying that the PANSS is an interval scale. For such interval scales straightforward calculation of relative changes is not appropriate. To calculate outcome criteria based on a percent change as, e.g., the widely accepted response criterion, the scale has to be transformed into a ratio scale beforehand. Recent publications have already pointed out the pitfall that ignoring the scale level (interval vs. ratio scale) leads to a set of mathematical problems, potentially resulting in erroneous results concerning the efficacy of the treatment.</p> <p>Methods</p> <p>A Pubmed search based on the PRISMA statement of the highest-ranked psychiatric journals (search terms "PANSS" and "response") was carried out. All articles containing percent changes were included and methods of percent change calculation were analysed.</p> <p>Results</p> <p>This systematic literature research shows that the majority of authors (62%) actually appear to use incorrect calculations. In most instances the method of calculation was not described in the manuscript.</p> <p>Conclusions</p> <p>These alarming results underline the need for standardized procedures for PANSS calculations.</p

An r -process enhanced star in the dwarf galaxy Tucana III

Chemically peculiar stars in dwarf galaxies provide a window for exploring the birth environment of stars with varying chemical enrichment. We present a chemical abundance analysis of the brightest star in the newly discovered ultra-faint dwarf galaxy candidate Tucana III. Because it is particularly bright for a star in an ultra-faint Milky Way (MW) satellite, we are able to measure the abundance of 28 elements, including 13 neutron-capture species. This star, DES J235532.66−593114.9 (DES J235532), shows a mild enhancement in neutron-capture elements associated with the r-process and can be classified as an r-I star. DES J235532 is the first r-I star to be discovered in an ultra-faint satellite, and Tuc III is the second extremely low-luminosity system found to contain rprocess enriched material, after Reticulum II. Comparison of the abundance pattern of DES J235532 with r-I and r-II stars found in other dwarf galaxies and in the MW halo suggests a common astrophysical origin for the neutron-capture elements seen in all r-process enhanced stars. We explore both internal and external scenarios for the r-process enrichment of Tuc III and show that with abundance patterns for additional stars, it should be possible to distinguish between them

Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development