A modified single-loop reconstruction after pancreaticoduodenectomy reduces severity of postoperative pancreatic fistula in high-risk patients

Background

Double-loop (DL) reconstruction after pancreaticoduodenectomy (PD), diverting pancreatic from biliary secretions, has been reported to reduce rates and severity of postoperative pancreatic fistula (POPF) compared to single loop (SL) reconstruction at the price of prolonged operative duration. This study investigated the feasibility of a new reconstruction method combining the advantages of DL with the simplicity of SL in patients with high-risk pancreas.

Prevalence of goiter and urinary iodine status of 7-11-year-old children in Malatya province, Turkey

Goiter prevalence and urinary iodine excretion levels were assessed in 568 schoolchildren (317 boys and 251 girls), aged 7-11 years, living in the Malatya province, a well-known endemic goiter area in Turkey. Five hundred sixty-eight children aged 7-11 years consented to thyroid gland palpation and provided a urine sample on the day of examination in April 2004. Median urinary iodine concentration for the total group was 66 microg/L. There was an association between presence of goiter or not and urinary iodine levels (67 microg/L versus 62 microg/L, p=0.000). The median urinary iodine concentration was lower in rural areas than in urban areas (54.6 microg/L versus 59.7 microg/L, respectively) and schoolchildren living in rural areas had significantly lower urinary iodine levels (p=0.000). In conclusion, the present study reports mild iodine deficiency in the Malatya province, despite a mandatory iodization program in Turkey which has been in force since 1998.     

Contribution of functional KIR3DL1 to ankylosing spondylitis

Increasing evidence points to a role for killer immunoglobulin-like receptors (KIRs) in the development of autoimmune diseases. In particular, a positive association of KIR3DS1 (activating receptor) and a negative association of KIR3DL1 (inhibitory receptor) alleles with ankylosing spondylitis (AS) have been reported by several groups. However, none of the studies analyzed these associations in the context of functionality of polymorphic KIR3DL1. To better understand how the KIR3DL1/3DS1 genes determine susceptibility to AS, we analyzed the frequencies of alleles and genotypes encoding functional (KIR3DL1*F) and non-functional (KIR3DL1*004) receptors. We genotyped 83 AS patients and 107 human leukocyte antigen (HLA)-B27-positive healthy controls from the Russian Caucasian population using a two-stage sequence-specific primer PCR, which distinguishes KIR3DS1, KIR3DL1*F and KIR3DL1*004 alleles. For the patients carrying two functional KIR3DL1 alleles, those alleles were additionally genotyped to identify KIR3DL1*005 and KIR3DL1*007 alleles, which are functional but are expressed at low levels. KIR3DL1 was negatively associated with AS at the expense of KIR3DL1*F but not of KIR3DL1*004. This finding indicates that the inhibitory KIR3DL1 receptor protects against the development of AS and is not simply a passive counterpart of the segregating KIR3DS1 allele encoding the activating receptor. However, analysis of genotype frequencies indicates that the presence of KIR3DS1 is a more important factor for AS susceptibility than the absence of KIR3DL1*F. The activation of either natural killer (NK) or T cells via the KIR3DS1 receptor can be one of the critical events in AS development, while the presence of the functional KIR3DL1 receptor has a protective effect. Nevertheless, even individuals with a genotype that carried two inhibitory KIR3DL1 alleles expressed at high levels could develop AS.     

Electrocatalytic Properties of Mixed-Oxide-Containing Composite-Supported Platinum for Polymer Electrolyte Membrane (PEM) Fuel Cells

TiO₂-based mixed oxide–carbon composite supports have been suggested to provide enhanced stability for platinum (Pt) electrocatalysts in polymer electrolyte membrane (PEM) fuel cells. The addition of molybdenum (Mo) to the mixed oxide is known to increase the CO tolerance of the electrocatalyst. In this work Pt catalysts, supported on Ti_1−xMo_xO₂–C composites with a 25/75 oxide/carbon mass ratio and prepared from different carbon materials (C: Vulcan XC-72, unmodified and functionalized Black Pearls 2000), were compared in the hydrogen oxidation reaction (HOR) and in the oxygen reduction reaction (ORR) with a commercial Pt/C reference catalyst in order to assess the influence of the support on the electrocatalytic behavior. Our aim was to perform electrochemical studies in preparation for fuel cell tests. The ORR kinetic parameters from the Koutecky–Levich plot suggested a four-electron transfer per oxygen molecule, resulting in H₂O. The similarity between the Tafel slopes suggested the same reaction mechanism for electrocatalysts supported by these composites. The HOR activity of the composite-supported electrocatalysts was independent of the type of carbonaceous material. A noticeable difference in the stability of the catalysts appeared only after 5000 polarization cycles; the Black Pearl-containing sample showed the highest stability.     

High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies

Rearrangements of T- and B-cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies. Currently, rearrangements of three out of four TCR and all BCR loci are used for this purpose. The fourth TCR gene, TRA, has not been used so far due to the lack of a method for its rearrangement detection in genomic DNA. Here we propose the first high-throughput sequencing based method for the identification of clonal TRA gene rearrangements at the DNA level. The method is based on target amplification of the rearranged TRA locus using an advanced multiplex polymerase chain reaction system and high-throughput sequencing, and has been tested on DNA samples from peripheral blood of healthy donors. Combinations of all functional V- and J-segments were detected, indicating the high sensitivity of the method. Additionally, we identified clonal TRA rearrangements in 57 out of 112 tested DNA samples of patients with various T-lineage lymphoproliferative disorders. The method fills the existing gap in utilizing the TRA gene for a wide range of studies, including clonality assessment, MRD monitoring and clonal evolution analysis in different lymphoid malignancies.     

Next generation sequencing for TCR repertoire profiling: Platform‐specific features and correction algorithms

The TCR repertoire is a mirror of the human immune system that reflects processes caused by infections, cancer, autoimmunity, and aging. Next generation sequencing (NGS) is becoming a powerful tool for deep TCR profiling; yet, questions abound regarding the methodological approaches for sample preparation and correct data interpretation. Accumulated PCR and sequencing errors along with library preparation bottlenecks and uneven PCR efficiencies lead to information loss, biased quantification, and generation of huge artificial TCR diversity. Here, we compare Illumina, 454, and Ion Torrent platforms for individual TCR profiling, evaluate the rate and character of errors, and propose advanced platform‐specific algorithms to correct massive sequencing data. These developments are applicable to a wide variety of next generation sequencing applications. We demonstrate that advanced correction allows the removal of the majority of artificial TCR diversity with concomitant rescue of most of the sequencing information. Thus, this correction enhances the accuracy of clonotype identification and quantification as well as overall TCR diversity measurements.     

A smart 19F and 1H MRI probe with self‐immolative linker as a versatile tool for detection of enzymes

Here we report on a dual‐modal ¹⁹F and ¹H MRI paramagnetic probe with a self‐immolative linker, Gd–DOMF–Gal. The enzymatic conversion of this probe by β‐galactosidase resulted in a simultaneous turning on of the fluorine signal and changed ability of the Gd³⁺ complex to modulate the ¹H MR signal intensity of the surrounding water molecules. A versatile imaging platform for monitoring a variety of enzymes by ¹⁹F and ¹H MRI using this molecular design is proposed. Copyright © 2012 John Wiley & Sons, Ltd.     

T‐cell receptor and B‐cell receptor repertoire profiling in adaptive immunity

B‐cell receptors and T‐cell receptors are the key molecules responsible for specific antigen recognition in adaptive immunity. The huge diversity of immune receptor repertoires constrained their comprehensive studies in the past. More recently, however, high‐throughput sequencing based techniques have revolutionized the field of immune receptor repertoire profiling enabling new insights into the development and function of the adaptive immune system. In this review we describe current methods for immune receptor profiling and software tools used for repertoire reconstruction from raw sequencing data. We also provide examples of how immune repertoire profiling can be used to study adaptive immunity in disease and in the course of organ and bone marrow transplantation.