Preclinical Assessment of Adjunctive tPA and DNase for Peritoneal Dialysis Associated Peritonitis

A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.     

Single Session Imaging of Cerebellum at 7 Tesla: Obtaining Structure and Function of Multiple Motor Subsystems in Individual Subjects

The recent increase in the use of high field MR systems is accompanied by a demand for acquisition techniques and coil systems that can take advantage of increased power and accuracy without being susceptible to increased noise. Physical location and anatomical complexity of targeted regions must be considered when attempting to image deeper structures with small nuclei and/or complex cytoarchitechtonics (i.e. small microvasculature and deep nuclei), such as the brainstem and the cerebellum (Cb). Once these obstacles are overcome, the concomitant increase in signal strength at higher field strength should allow for faster acquisition of MR images. Here we show that it is technically feasible to quickly and accurately detect blood oxygen level dependent (BOLD) signal changes and obtain anatomical images of Cb at high spatial resolutions in individual subjects at 7 Tesla in a single one-hour session. Images were obtained using two high-density multi-element surface coils (32 channels in total) placed beneath the head at the level of Cb, two channel transmission, and three-dimensional sensitivity encoded (3D, SENSE) acquisitions to investigate sensorimotor activations in Cb. Two classic sensorimotor tasks were used to detect Cb activations. BOLD signal changes during motor activity resulted in concentrated clusters of activity within the Cb lobules associated with each task, observed consistently and independently in each subject: Oculomotor vermis (VI/VII) and CrusI/II for pro- and anti-saccades; ipsilateral hemispheres IV-VI for finger tapping; and topographical separation of eye- and hand- activations in hemispheres VI and VIIb/VIII. Though fast temporal resolution was not attempted here, these functional patches of highly specific BOLD signal changes may reflect small-scale shunting of blood in the microvasculature of Cb. The observed improvements in acquisition time and signal detection are ideal for individualized investigations such as differentiation of functional zones prior to surgery.     

The postnatal ontogeny of the sexually dimorphic vocal apparatus in goitred gazelles (Gazella subgutturosa)

This study quantitatively documents the progressive development of sexual dimorphism of the vocal organs along the ontogeny of the goitred gazelle (Gazella subgutturosa). The major, male‐specific secondary sexual features, of vocal anatomy in goitred gazelle are an enlarged larynx and a marked laryngeal descent. These features appear to have evolved by sexual selection and may serve as a model for similar events in male humans. Sexual dimorphism of larynx size and larynx position in adult goitred gazelles is more pronounced than in humans, whereas the vocal anatomy of neonate goitred gazelles does not differ between sexes. This study examines the vocal anatomy of 19 (11 male, 8 female) goitred gazelle specimens across three age‐classes, that is, neonates, subadults and mature adults. The postnatal ontogenetic development of the vocal organs up to their respective end states takes considerably longer in males than in females. Both sexes share the same features of vocal morphology but differences emerge in the course of ontogeny, ultimately resulting in the pronounced sexual dimorphism of the vocal apparatus in adults. The main differences comprise larynx size, vocal fold length, vocal tract length, and mobility of the larynx. The resilience of the thyrohyoid ligament and the pharynx, including the soft palate, and the length changes during contraction and relaxation of the extrinsic laryngeal muscles play a decisive role in the mobility of the larynx in both sexes but to substantially different degrees in adult females and males. Goitred gazelles are born with an undescended larynx and, therefore, larynx descent has to develop in the course of ontogeny. This might result from a trade‐off between natural selection and sexual selection requiring a temporal separation of different laryngeal functions at birth and shortly after from those later in life. J. Morphol. 277:826–844, 2016. © 2016 Wiley Periodicals, Inc.     

Trainmasters or Easyjet pilots? Historical production,labor organizing,and the Spanish engine drivers’ union

This article presents an analysis of the relationship between historical memory and the emergence and reproduction of a specific model of unionism. I argue that in order to understand the militant particularism of the Spanish engine drivers, we need to look at the historical representations that it is embedded in. Recourse to a generational framework makes possible the sustained presentation of the union as a case of successful workers’ organizing, in spite of evidence to the contrary. The historical ethnographic analysis of SEMAF, the Spanish engine drivers’ union, contributes to the analysis of historical memory within the contemporary anthropology of class. The article contributes to theoretical debates in the anthropology of class by reclaiming Michel Trouillot’s conceptualization of the historical process. Two aspects of Trouillot’s work are singled out: his dynamic understanding of the process of historical production and the corollary formulation of the overlapping capacities in which people participate in it (as agents, actors, and subjects) and his emphasis on the importance of expanding scholarly views of the field of historical production.     

Brain Intraventricular Injection of Amyloid-β in Zebrafish Embryo Impairs Cognition and Increases Tau Phosphorylation,Effects Reversed by Lithium

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no effective treatment and commonly diagnosed only on late stages. Amyloid-β (Aβ) accumulation and exacerbated tau phosphorylation are molecular hallmarks of AD implicated in cognitive deficits and synaptic and neuronal loss. The Aβ and tau connection is beginning to be elucidated and attributed to interaction with different components of common signaling pathways. Recent evidences suggest that non-fibrillary Aβ forms bind to membrane receptors and modulate GSK-3β activity, which in turn phosphorylates the microtubule-associated tau protein leading to axonal disruption and toxic accumulation. Available AD animal models, ranging from rodent to invertebrates, significantly contributed to our current knowledge, but complementary platforms for mechanistic and candidate drug screenings remain critical for the identification of early stage biomarkers and potential disease-modifying therapies. Here we show that Aβ1–42 injection in the hindbrain ventricle of 24 hpf zebrafish embryos results in specific cognitive deficits and increased tau phosphorylation in GSK-3β target residues at 5dpf larvae. These effects are reversed by lithium incubation and not accompanied by apoptotic markers. We believe this may represent a straightforward platform useful to identification of cellular and molecular mechanisms of early stage AD-like symptoms and the effects of neuroactive molecules in pharmacological screenings.     

<Emphasis Type="Italic">Staphylococcus epidermidis</Emphasis>: A differential trait of the fecal microbiota of breast-fed infants

Background  

Breast milk is an important source of staphylococci and other bacterial groups to the infant gut. The objective of this work was to analyse the bacterial diversity in feces of breast-fed infants and to compare it with that of formula-fed ones. A total of 23 women and their respective infants (16 breast-fed and 7 formula-fed) participated in the study. The 16 women and their infants provided a sample of breast milk and feces, respectively, at days 7, 14, and 35. The samples were plated onto different culture media. Staphylococcal and enterococcal isolates were submitted to genetic profiling and to a characterization scheme, including detection of potential virulence traits and sensitivity to antibiotics.     

Differential apoptotic pathways activated in response to Cu-induced or HOCl-induced LDL oxidation in U937 monocytic cell line

We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or copper (Cu).Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis via a caspase-independent mechanism, with no activation of pro-caspase-3, but via the release of apoptosis inducing factor (AIF) from mitochondria.The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types.     

Oxidation-Reduction Sequence for the Synthesis of Peracylated Fluorodeoxy Pentofuranosides

Abstract

Oxidation of 1a with DMSO-acetic or trifluoroacetic anhydride led to the formation of a mixture of epimeric gem-diols 2 and 3 in the ratios of ?3:1 and ?7:1, respectively. Reduction of this mixture with NaBH₄ followed by benzoylation and chromatography afforded 4a and 5a.     

Alpha-Particle-Induced Complex Chromosome Exchanges Transmitted through Extra-Thymic Lymphopoiesis In Vitro Show Evidence of Emerging Genomic Instability

Human exposure to high-linear energy transfer α-particles includes environmental (e.g. radon gas and its decay progeny), medical (e.g. radiopharmaceuticals) and occupational (nuclear industry) sources. The associated health risks of α-particle exposure for lung cancer are well documented however the risk estimates for leukaemia remain uncertain. To further our understanding of α-particle effects in target cells for leukaemogenesis and also to seek general markers of individual exposure to α-particles, this study assessed the transmission of chromosomal damage initially-induced in human haemopoietic stem and progenitor cells after exposure to high-LET α-particles. Cells surviving exposure were differentiated into mature T-cells by extra-thymic T-cell differentiation in vitro. Multiplex fluorescence in situ hybridisation (M-FISH) analysis of naïve T-cell populations showed the occurrence of stable (clonal) complex chromosome aberrations consistent with those that are characteristically induced in spherical cells by the traversal of a single α-particle track. Additionally, complex chromosome exchanges were observed in the progeny of irradiated mature T-cell populations. In addition to this, newly arising de novo chromosome aberrations were detected in cells which possessed clonal markers of α-particle exposure and also in cells which did not show any evidence of previous exposure, suggesting ongoing genomic instability in these populations. Our findings support the usefulness and reliability of employing complex chromosome exchanges as indicators of past or ongoing exposure to high-LET radiation and demonstrate the potential applicability to evaluate health risks associated with α-particle exposure.