Review of machine perfusion studies in vascularized composite allotransplant preservation

The applications of Vascularized composite allotransplantation (VCA) are increasing since the first successful hand transplantation in 1998. However, the abundance of muscle tissue makes VCA's vulnerable to ischemia-reperfusion injury (IRI), which has detrimental effects on the outcome of the procedure, restricting allowable donor-to-recipient time and limiting its widespread use. The current clinical method is Static cold storage (SCS) and this allows only 6 h before irreversible damage occurs upon reperfusion. In order to overcome this obstacle, the focus of research has been shifted towards the prospect of ex-vivo perfusion preservation which already has an established clinical role in solid organ transplants especially in the last decade. In this comprehensive qualitative review, we compile the literature on all VCA machine perfusion models and we aim to highlight the essentials of an ex vivo perfusion set-up, the different strategies, and their associated outcomes

The Highly Energetic Expansion of SN2010bh Associated with GRB 100316D

We present the spectroscopic and photometric evolution of the nearby (z = 0.059) spectroscopically confirmed type Ic supernova, SN 2010bh, associated with the soft, long-duration gamma-ray burst (X-ray flash) GRB 100316D. Intensive follow-up observations of SN 2010bh were performed at the ESO Very Large Telescope (VLT) using the X-shooter and FORS2 instruments. Owing to the detailed temporal coverage and the extended wavelength range (3000--24800 A), we obtained an unprecedentedly rich spectral sequence among the hypernovae, making SN 2010bh one of the best studied representatives of this SN class. We find that SN 2010bh has a more rapid rise to maximum brightness (8.0 +/- 1.0 rest-frame days) and a fainter absolute peak luminosity (L_bol~3e42 erg/s) than previously observed SN events associated with GRBs. Our estimate of the ejected (56)Ni mass is 0.12 +/- 0.02 Msun. From the broad spectral features we measure expansion velocities up to 47,000 km/s, higher than those of SNe 1998bw (GRB 980425) and 2006aj (GRB 060218). Helium absorption lines He I lambda5876 and He I 1.083 microm, blueshifted by ~20,000--30,000 km/s and ~28,000--38,000 km/s, respectively, may be present in the optical spectra. However, the lack of coverage of the He I 2.058 microm line prevents us from confirming such identifications. The nebular spectrum, taken at ~186 days after the explosion, shows a broad but faint [O I] emission at 6340 A. The light-curve shape and photospheric expansion velocities of SN 2010bh suggest that we witnessed a highly energetic explosion with a small ejected mass (E_k ~ 1e52 erg and M_ej ~ 3 Msun). The observed properties of SN 2010bh further extend the heterogeneity of the class of GRB supernovae.Comment: 37 pages and 12 figures (one-column pre-print format), accepted for publication in Ap

Lyman continuum leakage in faint star-forming galaxies at redshift z=3-3.5 probed by gamma-ray bursts

Context. The identification of the sources that reionized the Universe and their specific contribution to this process are key missing pieces of our knowledge of the early Universe. Faint star-forming galaxies may be the main contributors to the ionizing photon budget during the epoch of reionization (EoR), but their escaping photons cannot be detected directly due to inter-galactic medium opacity. Hence, it is essential to characterize the properties of faint galaxies with significant Lyman continuum (LyC) photon leakage up to z 4 to define indirect indicators allowing analogues to be found at the highest redshift. Aims. Long gamma-ray bursts (LGRB) explode typically in star-forming regions of faint, star-forming galaxies. Through LGRB afterglow spectroscopy it is possible to detect directly LyC photons. Our aim is to use LGRBs as tools to study LyC leakage from faint, star-forming galaxies at high redshift. Methods. Here we present the observations of LyC emission in the afterglow spectra of GRB 191004B at z = 3:5055, together with those of the other two previously known LyC-emitting LGRB (GRB 050908 at z = 3:3467, and GRB 060607A at z = 3:0749), to determine their LyC escape fraction and compare their properties. Results. From the afterglow spectrum of GRB 191004B we determine a neutral hydrogen column density at the LGRB redshift of og(NHI/cm. 2) =17:2 0:15, and negligible extinction (AV = 0:03 0:02 mag). The only metal absorption lines detected are C iv and Si iv. In contrast to GRB 050908 and GRB 060607A, the host galaxy of GRB 191004B displays significant Ly emission. From its Ly emission and the non-detection of Balmer emission lines we constrain its star-formation rate (SFR) to 1 SFR 4:7 M yr. 1. We fit the Ly emission with a shell model and find parameters values consistent with the observed ones. The absolute (relative) LyC escape fractions we find for GRB 191004B, GRB 050908 and GRB 060607A are of 0:35+0:10 .0:11 (0:43+0:12 .0:13 ), 0:08+0:05.0:04(0:08+0:05.0:04) and :20+0:05.0:05(0:45+ 0:15.0:15), respectively. We compare the LyC escape fraction of LGRBs to the values of other LyC emitters found from the literature, showing that LGRB afterglows can be powerful tools to study LyC escape for faint high-redshift star-forming galaxies. Indeed we could push LyC leakage studies to much higher absolute magnitudes. The host galaxies of the three LGRB presented here have all M1600 > .19:5 mag, with the GRB 060607A host at M1600 > .16 mag. LGRB hosts may therefore be particularly suitable for exploring the ionizing escape fraction in galaxies that are too faint or distant for conventional techniques. Furthermore the time investment is very small compared to galaxy studies

Intestinal intraepithelial lymphocyte-enterocyte crosstalk regulates production of bactericidal angiogenin 4 by Paneth cells upon microbial challenge

Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation of their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells and intestinal intraepithelial lymphocytes (iIELs) that leads to antimicrobial protein (AMP) production by Paneth cells. Mice lacking γδ iIELs (TCRδ(-/-)) express significantly reduced levels of the AMP angiogenin 4 (Ang4). These mice were also unable to up-regulate Ang4 production following oral challenge by Salmonella, leading to higher levels of mucosal invasion compared to their wild type counterparts during the first 2 hours post-challenge. The transfer of γδ iIELs from wild type (WT) mice to TCRδ(-/-) mice restored Ang4 production and Salmonella invasion levels were reduced to those obtained in WT mice. The ability to restore Ang4 production in TCRδ(-/-) mice was shown to be restricted to γδ iIELs expressing Vγ7-encoded TCRs. Using a novel intestinal crypt co-culture system we identified a putative pathway of Ang4 production initiated by exposure to Salmonella, intestinal commensals or microbial antigens that induced intestinal epithelial cells to produce cytokines including IL‑23 in a TLR-mediated manner. Exposure of TCR-Vγ7(+) γδ iIELs to IL-23 promoted IL‑22 production, which triggered Paneth cells to secrete Ang4. These findings identify a novel role for γδ iIELs in mucosal defence through sensing immediate epithelial cell cytokine responses and influencing AMP production. This in turn can contribute to the maintenance of intestinal microbial homeostasis and epithelial barrier function, and limit pathogen invasion

2020 Proceedings of the 3rd International Conference on Trauma Surgery Technology in Giessen

The 3 rd event of the Giessen International Conference on Trauma Surgery Technology on October, the 17th 2020 was hosted on Zoom in accordance with the worldwide corona situation. Dr Mieczakowski, Dr Yu, and Wolfram drafted in 2018 from Jan’s apartment in Bremen the manuscript which was submitted to and approved for funding by the Deutsche Forschungsgemeinschaft (DFG). At that time, we had no idea what substantial changes the conferencing concept would require. This is why we would like to thank again Michele. She first planned this year’s event after the 2019 date and then in the spring of 2020 had to replan for the new situation

Algae Biodiesel

With increasing fuel prices, environmental concerns, and a growing transportation sector the United States will need to cut down on petroleum based fuels while investing and researching in various renewable energy sources. This study examined different strains, harvesting, and extraction methods of algae for production of algae biodiesel with a goal of determining the potential impact algae biodiesel can make on the economy, the environment and reducing emissions in the United States

The occurrence of different intrusive errors in patients with Alzheimer's disease, multiple cerebral infarctions, and major depression

Recent evidence suggests that specific types of intrusive errors may occur more often in the protocols of Alzheimer's disease (AD) patients than in those of patients diagnosed with other types of dementia. Using the FULD Object Memory Evaluation, we documented the occurrence of five qualitatively different types of intrusive errors for mildly and moderately impaired patients with AD and multiple cerebral infarctions (MCI). Depressed and normal elderly controls were also studied. Despite an equivalent degree of impairment on a broad array of neuropsychological measures, mildly impaired AD patients evidenced greater deficits on a measure tapping retrieval from semantic memory and demonstrated a higher occurrence of specific types of intrusive errors relative to their mildly impaired MCI counterparts. Further, both of these measures were highly correlated, suggesting that these indices may be particularly sensitive to semantic dysfunction associated with early AD

Lesions in Teichoic Acid Biosynthesis in Staphylococcus aureus Lead to a Lethal Gain of Function in the Otherwise Dispensable Pathway

An extensive study of teichoic acid biosynthesis in the model organism Bacillus subtilis has established teichoic acid polymers as essential components of the gram-positive cell wall. However, similar studies pertaining to therapeutically relevant organisms, such as Staphylococcus aureus, are scarce. In this study we have carried out a meticulous examination of the dispensability of teichoic acid biosynthetic enzymes in S. aureus. By use of an allelic replacement methodology, we examined all facets of teichoic acid assembly, including intracellular polymer production and export. Using this approach we confirmed that the first-acting enzyme (TarO) was dispensable for growth, in contrast to dispensability studies in B. subtilis. Upon further characterization, we demonstrated that later-acting gene products (TarB, TarD, TarF, TarIJ, and TarH) responsible for polymer formation and export were essential for viability. We resolved this paradox by demonstrating that all of the apparently indispensable genes became dispensable in a tarO null genetic background. This work suggests a lethal gain-of-function mechanism where lesions beyond the initial step in wall teichoic acid biosynthesis render S. aureus nonviable. This discovery poses questions regarding the conventional understanding of essential gene sets, garnered through single-gene knockout experiments in bacteria and higher organisms, and points to a novel drug development strategy targeting late steps in teichoic acid synthesis for the infectious pathogen S. aureus

The Cooperative Health Research in South Tyrol (CHRIS) study: Rationale, objectives, and preliminary results

The Cooperative Health Research In South Tyrol (CHRIS) study is a population-based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment