Injection drug use before and after liver transplantation: a retrospective multicenter analysis on incidence and outcome

Injecting drug use (IDU) before and after liver transplantation (LT) is poorly described. The aim of this study was to quantify relapse and survival in this population and to describe the causes of mortality after LT.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Presentation, microsurgical therapy, and clinical outcomes in three cases of expanding melanonychia of the nail unit in children

The management of expanding melanonychia in childhood is controversial. Here, we present three cases and discuss their operating indications and reconstruction. Between January 1, 1995 and December 31, 2007, one boy and two girls, were operated for expanding melanonychia, involving the thumb, index finger or the middle finger. They were 2, 4, and 7 years at the time of surgery. A complete resection of the nail plate was performed followed by a direct finger reconstruction using a free short-pedicle vascularized nail flap of the toe. Histology showed a junctional nevus in all cases. The follow-ups were after 2, 3, and 5 years and without any complications or recurrence. Regarding reconstruction, the mean Foucher and Leclère score were, respectively, 17 and 16 points. It is concluded that for expanding melanonychia, in case of doubt, an examination of the entire lesion is necessary. Reconstruction of the nail unit after wide excision with nail plate ablation can be performed using microsurgery as discussed below. However, new guidelines on shave biopsy can make this microsurgical procedure obsolete.

Development of a genotyping microarray for Usher syndrome

BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool.

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

The European Modern Pollen Database (EMPD) project

Modern pollen samples provide an invaluable research tool for helping to interpret the quaternary fossil pollen record, allowing investigation of the relationship between pollen as the proxy and the environmental parameters such as vegetation, land-use, and climate that the pollen proxy represents. The European Modern Pollen Database (EMPD) is a new initiative within the European Pollen Database (EPD) to establish a publicly accessible repository of modern (surface sample) pollen data. This new database will complement the EPD, which at present holds only fossil sedimentary pollen data. The EMPD is freely available online to the scientific community and currently has information on almost 5,000 pollen samples from throughout the Euro-Siberian and Mediterranean regions, contributed by over 40 individuals and research groups. Here we describe how the EMPD was constructed, the various tables and their fields, problems and errors, quality controls, and continuing efforts to improve the available data.

Erratum to: The European Modern Pollen Database (EMPD) project

Unfortunately, the list of authors contains a number of duplications, omissions and other errors in the original publication of the article. The correct list appears in this erratum.

A Staphylococcus xylosus isolate with a new mecC allotype

Recently, a novel variant of mecA known as mecC (mecA(LGA251)) was identified in Staphylococcus aureus isolates from both humans and animals. In this study, we identified a Staphylococcus xylosus isolate that harbors a new allotype of the mecC gene, mecC1. Whole-genome sequencing revealed that mecC1 forms part of a class E mec complex (mecI-mecR1-mecC1-blaZ) located at the orfX locus as part of a likely staphylococcal cassette chromosome mec element (SCCmec) remnant, which also contains a number of other genes present on the type XI SCCmec.

Anmerkungen zu den (spät)persischen Samaria-Bullen aus dem Wadi ed-Dalije. Hellenisches, Persisches und Lokaltraditionen im Grenzgebiet der Provinz Jehud

The present article deals exemplarily with the remarkable iconographic attestations connected with the Wadi ed-Daliye (WD) findings. The discussed bullae were attached to papyri which provide a clear dating of the hoard between 375-335 BCE. Considering style and convention the preserved motives are to be classified as Persian, Greek or Greco-Persian. A major goal of the following presentation is the contextualization of the very material; this is achieved by taking into account local parallels as well as relevant attestations of the dominant / “imperial” cultures of Persia and Greece. The correlation of motives with the (often more complex, more detailed or more contoured) examples stemming from the “source-cultures” follows a clear agenda: It is methodologically based on the approach that was employed by Silvia Schroer and Othmar Keel throughout the project „Die Ikonographie Palästinas/Israels und der Alte Orient (IPIAO). Eine Religionsgeschichte in Bildern” (2005, 23ff). The WD-findings demand a careful analysis since the influencing cultures behind the imagery are deeply rooted in the field of Greek mythology and iconography. Special attention has to be drawn to the bullae, as far as excavated, from a huge Punic temple archive of Carthago (Berges 1997 and 2002) as well as those from the archive of the satrap seat in Daskyleion in the Northwest of Asia Minor (Kaptan 2002), which are chronologically close (end 5th and 4th century BCE) to the WD-finds. Not each and every single motive and artifact of the WD-corpus comprising more than 120 items can be dealt with in detail throughout the following pages. We refer to the editio princeps by Leith (1990, 1997) respectively to the concerning chapter in Keel’s Corpus volume II (Keel 2010, 340-379). The article gives a brief history of research (2.), some basic remarks on the development of style (3.) and a selection of detail-studies (4.). A crosscheck with other relevant corpora of stamp-seals (5.) as well as a compressed synthesis (6.) are contributions in order to characterize and classify the unique iconographic assemblage. There are rather few references to the late Persian coins from Samaria (Meshorer/Qedar 1999), which have been impressed about contemporaneous with the WD-bullae (372-333 BCE), as there is an article by Patrick Wyssmann in this volume about that specific corpus. Through the perspective of the late Persian iconography, Samaria appears as a dazzling metropolis at the crossroads of Greek and Persian culture, which is far away from a strict and revolutionary religious orthodoxy

Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.

BACKGROUND The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. METHODS We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. RESULTS A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. CONCLUSIONS Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

Le temps de la défiguration. À propos de la versification dans Les Pâques à New York

Cet article est une première contribution à une nouvelle compréhension de la versification de Cendrars, qui a été décrite comme appartenant au «vers libre classique» (Roubaud). Dans Les Pâques à New York, la fréquence des alexandrins réguliers incite à ramener des vers apparemment non réguliers au schéma de l’alexandrin. Il s’ensuit une défiguration de l’alexandrin qui fait écho sur le plan thématique à celle du Christ, dont les Pâques n’indiquent que la passion et non la résurrection.

Evidence for an Ancestral Association of Human Coronavirus 229E with Bats.

UNLABELLED We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.