Clostridium difficile colitis in patients after kidney and pancreas-kidney transplantation

Limited data exist about Clostridium difficile colitis (CDC) in solid organ transplant patients. Between 1/1/99 and 12/31/02, 600 kidney and 102 pancreas–kidney allograft recipients were transplanted. Thirty-nine (5.5%) of these patients had CDC on the basis of clinical and laboratory findings. Of these 39 patients, 35 have information available for review. CDC developed at a median of 30 days after transplantation, and the patients undergoing pancreas–kidney transplantation had a slightly higher incidence of CDC than recipients of kidney alone (7.8% vs. 4.5%, P> 0.05). All but one patient presented with diarrhea. Twenty-four patients (64.9%) were diagnosed in the hospital, and CDC occurred during first hospitalization in 14 patients (40%). Treatment was with oral metronidazole (M) in 33 patients (94%)and M + oral vancomycin (M + V) in 2 patients. Eight patients had recurrent CDC, which occurred at a median of 30 days (range 15–314) after the first episode. Two patients (5.7%) developed fulminant CDC, presented with toxic megacolon, and underwent colectomy. One of them died; the other patient survived after colectomy. CDC should be considered as a diagnosis in transplant patients with history of diarrhea after antibiotic use, and should be treated aggressively before the infection becomes complicated

On the dynamic mechanical properties of open-cell metal foams - A re-assessment of the 'simple-shock theory'

Metal foams are increasingly used for energy absorption especially in lightweight structures and to resist blast and impact loads. This requires an understanding of the dynamic response of these materials for modelling purposes. As a supplement to Tan et al., 2005a and Tan et al., 2005b, hereinafter referred to as T–L for brevity, this paper provides experimental data for the dynamic mechanical properties of open-cell Duocel® foams having a three-dimensional (3D) distribution of cells. These confirm significant enhancement of the foam’s compressive strength, accompanied by changes in their deformation pattern in certain loading régimes, particularly what has come to be described as the ‘shock’ régime by Zheng et al. (2012). This paper examines experimentally, in a similar fashion as T–L, how the structural response of the individual cell walls is affected by cell-shape anisotropy at the cell (meso)-scale and how this, in turn, alters the pattern of cell crushing and the dynamic, mechanical properties. The distinctive role of cell microinertia and ‘shock’ formation are discussed in relation to the mechanical properties measured for these 3D cylindrical specimens. For consistency the same procedures described in T–L are used. The features identified are shown to be consistent with those observed in finite-element simulations of two-dimensional (2D) honeycombs as estimated by the one-dimensional (1D) steady-shock theory summarised in T–L. The different deformation patterns that develop in the various loading régimes are categorised according to the compression rate/impact speed. Critical values of impact velocity, corresponding to the transition from one pattern to the other, are quantified and predictive formulae for the compressive uniaxial strengths in the directions of two of the principal axes of the material in each loading régime are derived and discussed. The accuracy of the predictive formula in T–L is shown to critically depend on the ‘densification strain’ of the foam specimens. This parameter and the discussion that follows could assist the formulation and validation of alternative theoretical/computational models on the dynamic deformation of such materials

Dynamic Covalent Synthesis of Crystalline Porous Graphitic Frameworks

Porous graphitic framework (PGF) is a two-dimensional (2D) material that has emerging energy applications. An archetype contains stacked 2D layers, the structure of which features a fully annulated aromatic skeleton with embedded heteroatoms and periodic pores. Due to the lack of a rational approach in establishing in-plane order under mild synthetic conditions, the structural integrity of PGF has remained elusive and ultimately limited its material performance. Here, we report the discovery of the unusual dynamic character of the C=N bonds in the aromatic pyrazine ring system under basic aqueous conditions, which enables the successful synthesis of a crystalline porous nitrogenous graphitic framework with remarkable in-plane order, as evidenced by powder X-ray diffraction studies and direct visualization using high-resolution transmission electron microscopy. The crystalline framework displays superior performance as a cathode material for lithium-ion batteries, outperforming the amorphous counterparts in terms of capacity and cycle stability. Insertion of well-defined, evenly spaced nanoscale pores into the two-dimensional (2D) layers of graphene invokes exciting properties due to the modulation of its electronic band gaps and surface functionalities. A bottom-up synthesis approach to such porous graphitic frameworks (PGFs) is appealing but also remains a great challenge. The current methods of building covalent organic frameworks rely on a small collection of thermodynamically reversible reactions. Such reactions are, however, inadequate in generating a fully annulated aromatic skeleton in PGFs. With the discovery of dynamic pyrazine formation, we succeeded in applying this linking chemistry to obtain a crystalline PGF material, which has displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries. We envision that the demonstrated success will open the door to a wide array of fully annulated 2D porous frameworks, which hold immense potential for clean energy applications. We report the unusual dynamic characteristics of the C=N bonds in the pyrazine ring promoted under basic aqueous conditions, which enables the successful synthesis of two-dimensional porous graphitic frameworks (PGFs) featuring fully annulated aromatic skeletons and periodic pores. The PGF displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries, far outperforming the amorphous counterparts in terms of capacity and cycle stability

Projections of the healthcare costs and disease burden due to hepatitis C infection under different treatment policies in Malaysia, 2018-2040

The World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis

Determinants of postnatal spleen tissue regeneration and organogenesis

Abstract The spleen is an organ that filters the blood and is responsible for generating blood-borne immune responses. It is also an organ with a remarkable capacity to regenerate. Techniques for splenic auto-transplantation have emerged to take advantage of this characteristic and rebuild spleen tissue in individuals undergoing splenectomy. While this procedure has been performed for decades, the underlying mechanisms controlling spleen regeneration have remained elusive. Insights into secondary lymphoid organogenesis and the roles of stromal organiser cells and lymphotoxin signalling in lymph node development have helped reveal similar requirements for spleen regeneration. These factors are now considered in the regulation of embryonic and postnatal spleen formation, and in the establishment of mature white pulp and marginal zone compartments which are essential for spleen-mediated immunity. A greater understanding of the cellular and molecular mechanisms which control spleen development will assist in the design of more precise and efficient tissue grafting methods for spleen regeneration on demand. Regeneration of organs which harbour functional white pulp tissue will also offer novel opportunities for effective immunotherapy against cancer as well as infectious diseases

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

Stem cell differentiation increases membrane-actin adhesion regulating cell blebability, migration and mechanics

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/K. S. is funded by an EPSRC PhD studentship. S.T. is funded by an EU Marie Curie Intra European Fellowship (GENOMICDIFF)