Severe babesiosis in an asplenic patient requiring red cell exchange

Corresponding author: William N. Rose, Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and ClinicsBabesiosis is a rare, tick-borne infectious disease, caused mostly by the parasite Babesia microti in the United States. It is frequently transmitted through the bite of the Ixodes scapularis tick. Babesiosis is characterized by red cell disruption and intravascular hemolysis. Severe cases can be life-threatening and are associated with asplenia, advanced age, and other causes of impaired immune function. Treatment is typically with antibiotics. However, for severe cases, the use of red cell exchange has been reported with debate about its efficacy. Here, we report a complex case of babesiosis with a parasitemia of 22% that required two red cell exchange procedures and multiple antibiotics in a patient with a history of asplenia.Xiaoyan Yang, Margarita C. Consing Gangelhoff, William N. Rose (Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics)Includes bibliographical references

Characterization of the cardiac ganglion in the crab Neohelice granulata and immunohistochemical evidence of GABA-like extrinsic regulation

The aim of the present work is to provide an anatomical description of the cardiac system in the crab Neohelice granulata and evidence of the presence of GABA by means of immunohistochemistry. The ganglionic trunk was found lying on the inner surface of the heart's dorsal wall. After dissection, this structure appeared as a Y-shaped figure with its major axis perpendicular to the major axis of the heart. Inside the cardiac ganglion, we identified four large neurons of 63.7 μm ± 3.7 in maximum diameter, which were similar to the motor neurons described in other decapods. All the GABA-like immunoreactivity (GABAi) was observed as processes entering mainly the ganglionic trunk and branching in slender varicose fibers, forming a network around the large neurons suggesting that GABAi processes contact them. Our findings strengthen previous results suggesting that the GABAergic system mediates the cardio-inhibitory response upon sensory stimulation.Fil: Yang, Margarita.Fil: Carbo, Martin.Fil: Freudenthal, Ramiro A. M..Fil: Hermitte, Gabriela

Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data.

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of haematological cancers and is currently being investigated for solid tumours, including high-grade glioma brain tumours. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumours. In this work, we use a mathematical model of predator-prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor T-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, proliferation, exhaustion, and persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyser to parametrize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted when compared with higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumour growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumour characteristics including tumour growth rate and antigen level to maximize therapeutic benefit

The role of school connectedness and friend contact in adolescent loneliness, and implications for physical health

JI was supported by the Medical Research Council (MC_UU_00022/1) and the Scottish Government Chief Scientist Office (SPHSU16). The HBSC 2013/14 study in Scotland was funded by NHS Health Scotland (now Public Health Scotland).The current study investigated how adolescents' loneliness relates to school connectedness, classmate support, teacher support, and offline and online communication with friends. We also examined the association between loneliness, physical health, and sleep. Data came from the Scottish Health Behavior in School-aged Children (HBSC). The total sample was 2983 adolescents (F = 1479 [49.6%]) aged 14-17 years (M = 15.66, SD = 0.39) from 117 secondary schools in Scotland. Results showed that (1) higher teacher support, classmate support, and offline contact with friends predicted lower levels of loneliness, (2) online friendship engagement predicted higher levels of loneliness, and (3) poor health and sleep were positively associated with loneliness. The study offers new findings, highlighting the role played by classmates/peers and teachers in reducing loneliness. Supporting previous research, we also found associations between loneliness, poor sleep, and worse physical health.Publisher PDFPeer reviewe

Polychlorinated biphenyls, Polybrominated biphenyls, Polychlorinated dibenzo-p-dioxins and Polychlorinated dibenzofurans

Environmental contamination levels, human exposure, toxicokinetics, and health effects of PCBs, PBBs, PCDDs/PCDFs are discussed

Indometacin loading and in vitro release properties from novel carbopol coated spherical mesoporous silica nanoparticles

Spherical MCM-41 silica nanosized particles were synthesized and post synthesis modified by 3-aminopropyltriethoxysilane (APTES) in order to prepare amino-functionalized carrier. Both types of silica particleswere loaded with indometacin and further coated with carbopol. The preservation of morphology and pore structure of the particles was observed by XRD, TEM and N2 physisorption. FT-IR spectroscopy revealed the interaction between carboxyl groups of indometacin and the amino groups of the functionalized MCM-41. Amino-functionalization of the carrier resulted in higher degree of indometacin loading in comparison to the parent MCM-41, 39% vs. 30%, respectively. The coating of drug loaded amino-MCM-41 silica particles with carbopol significantly reduced the initial burst release of indometacin. Both silica carriers demonstrated no cytotoxicity on HL-60 (acute myeloid leukemia) and K-562 (chronic myeloid leukemia) cell lines

A Deep Chandra ACIS Study of NGC 4151. III. the Line Emission and Spectral Analysis of the Ionization Cone

This paper is the third in a series in which we present deep Chandra ACIS-S imaging spectroscopy of the Seyfert 1 galaxy NGC 4151, devoted to study its complex circum-nuclear X-ray emission. Emission features in the soft X-ray spectrum of the bright extended emission (L[0.3-2keV]~10^40 erg/s) at r>130 pc (2") are consistent with the brighter OVII, OVIII, and NeIX lines seen in the Chandra HETGS and XMM-Newton RGS spectra below 2 keV. We construct emission line images of these features and find good morphological correlations with the narrow line region clouds mapped in [OIII]5007A. Self-consistent photoionization models provide good descriptions of the spectra of the large scale emission, as well as resolved structures, supporting the dominant role of nuclear photoionization, although displacement of optical and X-ray features implies a more complex medium. Collisionally ionized emission is estimated to be <12% of the extended emission. Presence of both low and high ionization spectral components and extended emission in the X-ray image perpendicular to the bicone indicates leakage of nuclear ionization, likely filtered through warm absorbers, instead of being blocked by a continuous obscuring torus. The ratios of [OIII]/soft X-ray flux are approximately constant (~15) for the 1.5 kpc radius spanned by these measurements, indicating a relatively constant ionization parameter, consistent with the photoionized outflow of a wind-like density profile. Using spatially resolved features, we estimate that the mass outflow rate in NGC 4151 is ~2Msun/yr at 130 pc and the kinematic power of the ionized outflow is 1.7x10^41 erg/s, approximately 0.3% of the bolometric luminosity of NGC 4151.Comment: 45 pages. 18 figures. Accepted to Ap

A Deep Chandra ACIS Study of NGC 4151. II. The Innermost Emission Line Region and Strong Evidence for Radio Jet-NLR Cloud Collision

We have studied the X-ray emission within the inner 150 pc radius of NGC 4151 by constructing high spatial resolution emission line images of OVII, OVIII, and NeIX. These maps show extended structures that are spatially correlated with the radio outflow and optical [OIII] emission. We find strong evidence for jet--gas cloud interaction, including morphological correspondences with regions of X-ray enhancement, peaks of near-infrared [FeII] emission, and optical clouds. In these regions, moreover, we find evidence of elevated NeIX/OVII ratios; the X-ray emission of these regions also exceeds that expected from nuclear photoionization. Spectral fitting reveals the presence of a collisionally ionized component. The thermal energy of the hot gas suggests that >0.1% of the estimated jet power is deposited into the host interstellar medium through interaction between the radio jet and the dense medium of the circum-nuclear region. We find possible pressure equilibrium between the collisionally ionized hot gas and the photoionized line-emitting cool clouds. We also obtain constraints on the extended iron and silicon fluorescent emission. Both lines are spatially unresolved. The upper limit on the contribution of an extended emission region to the Fe Kalpha emission is <5% of the total, in disagreement with a previous claim that 65% of the Fe Kalpha emission originates in the extended narrow line region.Comment: Accepted for publication in ApJ. 28 pages, 9 figure

A Deep Chandra ACIS Study of NGC 4151. I. the X-ray Morphology of the 3 kpc-diameter Circum-nuclear Region and Relation to the Cold Interstellar Medium

We report on the imaging analysis of 200 ks sub-arcsecond resolution Chandra ACIS-S observations of the nearby Seyfert 1 galaxy NGC 4151. Bright, structured soft X-ray emission is observed to extend from 30 pc to 1.3 kpc in the south-west from the nucleus, much farther than seen in earlier X-ray studies. The terminus of the north-eastern X-ray emission is spatially coincident with a CO gas lane, where the outflow likely encounters dense gas in the host galactic disk. X-ray emission is also detected outside the boundaries of the ionization cone, which indicates that the gas there is not completely shielded from the nuclear continuum, as would be the case for a molecular torus collimating the bicone. In the central r<200 pc region, the subpixel processing of the ACIS data recovers the morphological details on scales of <30~pc (<0.5") first discovered in Chandra HRC images. The X-ray emission is more absorbed towards the boundaries of the ionization cone, as well as perpendicular to the bicone along the direction of a putative torus in NGC 4151. The innermost region where X-ray emission shows the highest hardness ratio, is spatially coincident with the near-infrared resolved H_2 emission and dusty spirals we find in an HST V-H color image. The agreement between the observed H_2 line flux and the value predicted from X-ray-irradiated molecular cloud models supports photo-excitation by X-rays from the active nucleus as the origin of the H_2 line, although contribution from UV fluorescence or collisional excitation cannot be fully ruled out with current data. The discrepancy between the mass of cold molecular gas inferred from recent CO and near-infrared H_2 observations may be explained by the anomalous CO abundance in this X-ray dominated region. The total H_2 mass derived from the X-ray observation agrees with measurement in Storchi-Bergmann et al.Comment: 33 pages, 9 figures and 2 table