Liver transplantation for acute-on-chronic liver failure

Purpose: To evaluate the outcome of liver transplantation for acute-on-chronic liver failure. Patients and methods: From November 1991 to December 2007, 517 patients underwent liver transplantation at Queen Mary Hospital, Hong Kong. Among them, 149 had acute-on-chronic liver failure as defined in the recent Asian Pacific Association for the Study of Liver Consensus Meeting. Their clinical data were reviewed and their survival outcomes were compared with those of patients who underwent liver transplantation for fulminant hepatic failure and for cirrhosis only in the same period. Results: The patients with acute-on-chronic liver failure included 50 patients having acute exacerbation of chronic hepatitis B and 99 cirrhotic patients with acute deterioration. Their median model for end-stage liver disease scores were 35 and 37, respectively. Preoperative infection (35%), hepatorenal syndrome (38%), and respiratory failure (28.8%) were common. One hundred and three patients received living donor liver grafts and 46 patients received deceased donor liver grafts. The hospital mortality rate was 4.7%. The 5-year survival rates were 93.2% for patients with acute exacerbation of chronic hepatitis B and 90.5% for cirrhotic patients with acute deterioration. The results were similar to those of the patients with fulminant hepatic failure (n = 37) and the patients having cirrhosis only (n = 301). Conclusions: Liver transplantation for acute-on-chronic liver failure is life-saving, and the survival rates it attains are similar to those attained by transplantation for other liver conditions.published_or_final_versionSpringer Open Choice, 21 Feb 201

Mary Adams and the producer’s role in early BBC science broadcasts

Mary Adams was a science producer at the BBC from 1930–6. She is shown to have played a crucial role in shaping science broadcasts, in particular devising formats and styles of presentation. However, her approach is shown to have been primarily motivated by broadcasting considerations rather than by the popularisation of science. Through her interaction with scientists she helped to construct a new professional domain, that of the science-broadcasting professional, at a time when other producers were creating analogous roles in other areas of broadcasting. This paper is based largely on unpublished archival documents

Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

Oesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of intense research. The aim of the present study was to study the prognostic significance of Met, the hepatic growth factor (HGF) receptor and a possible target for therapy in comparison to cyclooxygenase-2 (COX-2). Tumour sections from 145 consecutive patients undergoing intentionally curative surgery for oesophageal adenocarcinoma were immunohistochemically analysed for Met and COX-2 expression. Clinicopathological data were prospectively collected for all patients. Patients with high Met expression had significantly reduced overall and disease-specific 5-year survival rates (P⩽0.001 and P⩽0.001, respectively) and were more likely to develop distant metastases (P=0.002) and local recurrences (P=0.004) compared to patients with low Met expression. High COX-2 expression tended to be correlated with poor long-term survival but this did not reach statistical significance. Expression of Met was recognised as a significant and independent prognostic factor by stage-specific analysis and multivariate analysis (relative risk=2.3; 95% CI=1.3–4.1). These findings support the importance of Met in oesophageal adenocarcinoma and support the concept of Met tyrosine kinase inhibition as (neo-) adjuvant treatment

Range of shoulder motion in patients with adhesive capsulitis; Intra-tester reproducibility is acceptable for group comparisons

<p>Abstract</p> <p>Background</p> <p>Measurements of range of motion play a key role in shoulder research. The purpose of this study is to investigate intra-observer reproducibility of measurements of active and passive range of motion in patients with adhesive capsulitis.</p> <p>Methods</p> <p>The study was carried out in a population consisting of 32 patients with clinical signs of adhesive capsulitis. A specified measurement protocol was used, and range of motion in affected and non-affected shoulders was measured twice for each patient with a one-week interval.</p> <p>Results</p> <p>For most of the investigated individual movements, test-retest differences in range of motion score of more than approximately 15° are not likely to occur as a result of measurement error only. Point-estimates for the intraclass correlation coefficient ranged from 0.61 to 0.93.</p> <p>Conclusion</p> <p>Range of motion of patients with adhesive capsulitis can be measured with acceptable reproducibility in settings where groups are compared. Scores for individual patients should be interpreted with caution.</p

Survival or Revival: Long-Term Preservation Induces a Reversible Viable but Non-Culturable State in Methane-Oxidizing Bacteria

Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB) has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry) and culturability (via most-probable number analysis and plating) of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT) as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC) state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium

Oligoasthenoteratozoospermia and Infertility in Mice Deficient for miR-34b/c and miR-449 Loci

Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation) are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA) gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449) that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility

Selective cancer-germline gene expression in pediatric brain tumors

Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2,8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways

Differential immunity as a factor influencing mussel hybrid zone structure

Interspecific hybridisation can alter fitness-related traits, including the response to pathogens, yet immunity is rarely investigated as a potential driver of hybrid zone dynamics, particularly in invertebrates. We investigated the immune response of mussels from a sympatric population at Croyde Bay, within the hybrid zone of Mytilus edulis and Mytilus galloprovincialis in Southwest England. The site is characterised by size-dependent variation in genotype frequencies, with a higher frequency of M. galloprovincialis alleles in large mussels, largely attributed to selective mortality in favour of the M. galloprovincialis genotype. To determine if differences in immune response may contribute to this size-dependent variation in genotype frequencies, we assessed the two pure species and their hybrids in their phagocytic abilities when subject to immune challenge as a measure of immunocompetence and measured the metabolic cost of mounting an antigen-stimulated immune response. Mussels identified as M. galloprovincialis had a greater immunocompetence response at a lower metabolic cost compared to mussels identified as M. edulis. Mussels identified as hybrids had intermediate values for both parameters, providing no evidence for heterosis but suggesting that increased susceptibility compared to M. galloprovincialis may be attributed to the M. edulis genotype. The results indicate phenotypic differences in the face of pathogenic infection, which may be a contributing factor to the differential mortality in favour of M. galloprovincialis, and the size-dependent variation in genotype frequencies associated with this contact zone. We propose that immunity may contribute to European mussel hybrid zone dynamics

Towards an integrated approach in surveillance of vector-borne diseases in Europe

Vector borne disease (VBD) emergence is a complex and dynamic process. Interactions between multiple disciplines and responsible health and environmental authorities are often needed for an effective early warning, surveillance and control of vectors and the diseases they transmit. To fully appreciate this complexity, integrated knowledge about the human and the vector population is desirable. In the current paper, important parameters and terms of both public health and medical entomology are defined in order to establish a common language that facilitates collaboration between the two disciplines. Special focus is put on the different VBD contexts with respect to the current presence or absence of the disease, the pathogen and the vector in a given location. Depending on the context, whether a VBD is endemic or not, surveillance activities are required to assess disease burden or threat, respectively. Following a decision for action, surveillance activities continue to assess trends

Variations in the Difference between Mean Sea Level measured either side of Cape Hatteras and Their Relation to the North Atlantic Oscillation

We consider the extent to which the difference in mean sea level (MSL) measured on the North American Atlantic coast either side of Cape Hatteras varies as a consequence of dynamical changes in the ocean caused by fluctuations in the North Atlantic Oscillation (NAO). From analysis of tide gauge data, we know that changes in MSL-difference and NAO index are correlated on decadal to century timescales enabling a scale factor of MSL-difference change per unit change in NAO index to be estimated. Changes in trend in the NAO index have been small during the past few centuries (when measured using windows of order 60–120 years). Therefore, if the same scale factor applies through this period of time, the corresponding changes in trend in MSL-difference for the past few centuries should also have been small. It is suggested thereby that the sea level records for recent centuries obtained from salt marshes (adjusted for long-term vertical land movements) should have essentially the same NAO-driven trends south and north of Cape Hatteras, only differing due to contributions from other processes such as changes in the Meridional Overturning Circulation or ‘geophysical fingerprints’. The salt marsh data evidently support this interpretation within their uncertainties for the past few centuries, and perhaps even for the past millennium. Recommendations are made on how greater insight might be obtained by acquiring more measurements and by improved modelling of the sea level response to wind along the shelf