Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

A novel framework for characterizing genomic haplotype diversity in the human immunoglobulin heavy chain locus

An incomplete ascertainment of genetic variation within the highly polymorphic immunoglobulin heavy chain locus (IGH) has hindered our ability to define genetic factors that influence antibody-mediated processes. Due to locus complexity, standard high-throughput approaches have failed to accurately and comprehensively capture IGH polymorphism. As a result, the locus has only been fully characterized two times, severely limiting our knowledge of human IGH diversity. Here, we combine targeted long-read sequencing with a novel bioinformatics tool, IGenotyper, to fully characterize IGH variation in a haplotype-specific manner. We apply this approach to eight human samples, including a haploid cell line and two mother-father-child trios, and demonstrate the ability to generate high-quality assemblies (>98% complete and >99% accurate), genotypes, and gene annotations, identifying 2 novel structural variants and 15 novel IGH alleles. We show multiplexing allows for scaling of the approach without impacting data quality, and that our genotype call sets are more accurate than short-read (>35% increase in true positives and >97% decrease in false-positives) and array/imputation-based datasets. This framework establishes a desperately needed foundation for leveraging IG genomic data to study population-level variation in antibody-mediated immunity, critical for bettering our understanding of disease risk, and responses to vaccines and therapeutics

GATA3 Expression Is Decreased in Psoriasis and during Epidermal Regeneration; Induction by Narrow-Band UVB and IL-4

Psoriasis is characterized by hyperproliferation of keratinocytes and by infiltration of activated Th1 and Th17 cells in the (epi)dermis. By expression microarray, we previously found the GATA3 transcription factor significantly downregulated in lesional psoriatic skin. Since GATA3 serves as a key switch in both epidermal and T helper cell differentiation, we investigated its function in psoriasis. Because psoriatic skin inflammation shares many characteristics of epidermal regeneration during wound healing, we also studied GATA3 expression under such conditions

JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes

JHDM1B is an evolutionarily conserved and ubiquitously expressed member of the JHDM (JmjC-domain-containing his- tone demethylase) family1\u20133. Because it contains an F-box motif, this protein is also known as FBXL10 (ref. 4). With the use of a genome-wide RNAi screen, the JHDM1B worm orthologue (T26A5.5) was identified as a gene that regulates growth5. In the mouse, four independent screens have identified JHDM1B as a putative tumour suppressor by retroviral insertion analysis6\u20139. Here we identify human JHDM1B as a nucleolar protein and show that JHDM1B preferentially binds the transcribed region of ribosomal DNA to repress the transcription of ribosomal RNA genes. We also show that repression of ribosomal RNA genes by JHDM1B is dependent on its JmjC domain, which is necessary for the specific demethylation of trimethylated lysine 4 on histone H3 in the nucleolus. In agreement with the notion that ribosomal RNA synthesis and cell growth are coupled processes, we show a JmjC-domain-dependent negative effect of JHDM1B on cell size and cell proliferation. Because aberrant ribosome biogenesis and the disruption of epigenetic control mechanisms contribute to cellular transformation, these results, together with the low levels of JHDM1B expression found in aggressive brain tumours, suggest a role for JHDM1B in cancer development

Os peroneum imaging: normal appearance and pathological findings

The os peroneum (OP) is a small sesamoid bone located inside the peroneus longus tendon (PLT), close to the cuboid. The OP can be the cause of pain and can be associated with lesions of the PLT. OP involvement in PLT disorders is frequently misdiagnosed by radiologists. Painful os peroneum syndrome (POPS) refers to a variety of conditions presenting with pain localized on the lateral aspect of the cuboid area. The syndrome can be observed as a consequence of local acute trauma such as ankle sprains or chronic overuse. Because of its intra-tendinous location, in tears of the peroneus longus tendon, the OP can show changes in its morphology or position, depending on the location of the tendon’s tear. Based on the level of the PLT tears, we propose a classification in three subtypes: tears localized proximal to the os peroneum (type I), at its level (type II) or distal to it (type III). These tears present with different changes on OP morphology or location. The aim of this article is to review the normal anatomy, imaging appearance and differential diagnosis of disorders of the OP as well as post-treatment imaging. Teaching points • PLT tears can be classified in three subtypes according to OP location. • POPS is characterized by pain on the lateral aspect of the cuboid. • OP involvement in PLT disorders is frequently misdiagnosed by radiologists

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy.

Peer reviewe

Association analysis of low-phosphorus tolerance in West African pearl millet using DArT markers

Pearl millet [Pennisetum glaucum (L.) R. Br.] is a food security crop in the harshest agricultural regions of the world. While low soil phosphorus (P) availability is a big constraint on its production, especially in West Africa (WA), information on genomic regions responsible for low-P tolerance in pearl millet is generally lacking. We present the first report on genetic polymorphisms underlying several plant P-related parameters, flowering time (FLO) and grain yield (GY) under P-limiting conditions based on 285 diversity array technology markers and 151 West African pearl millet inbred lines phenotyped in six environments in WA under both high-P and low-P conditions. Nine markers were significantly associated with P-related traits, nine markers were associated with FLO, whereas 13 markers were associated with GY each explaining between 5.5 and 15.9 % of the observed variation. Both constitutive and adaptive associations were observed for FLO and GY, with markers PgPb11603 and PgPb12954 being associated with the most stable effects on FLO and GY, respectively, across locations. There were a few shared polymorphisms between traits, especially P-efficiency-related traits and GY, implying possible colocation of genomic regions responsible for these traits. Our findings help bridge the gap between quantitative and molecular methods of studying complex traits like low-P tolerance in WA. However, validation of these markers is necessary to determine their potential applicability in marker-assisted selection programs targeting low-P environments, which are especially important in WA where resource-poor farmers are expected to be the hardest hit by the approaching global P crisis