Outcome of renal grafts after simultaneous kidney/ pancreas transplantation

Nineteen patients with endstage renal failure due to Type 1 (insulin-dependent) diabetes mellitus received simultaneous pancreas/kidney transplants using bladder drainage technique. Another group of 25 Type 1 diabetic patients received pancreas/kidney transplants by the duct occlusion technique. We observed a higher incidence of rejection episodes in the patients of the bladder drainage group than those in the duct occlusion group, 14 of 19 patients (74%) vs 7 of 25 (28%) respectively. Anti CD3 antibodies (Orthoclone, OKT3) as a part of induction treatment was used more often in the bladder drainage group (58%) than in the control group (20%)

The Rate and Molecular Spectrum of Spontaneous Mutations in Arabidopsis thaliana

To take complete advantage of information on within-species polymorphism and divergence from close relatives, one needs to know the rate and the molecular spectrum of spontaneous mutations. To this end, we have searched for de novo spontaneous mutations in the complete nuclear genomes of five Arabidopsis thaliana mutation accumulation lines that had been maintained by single-seed descent for 30 generations. We identified and validated 99 base substitutions and 17 small and large insertions and deletions. Our results imply a spontaneous mutation rate of 7 × 10−9 base substitutions per site per generation, the majority of which are G:C→A:T transitions. We explain this very biased spectrum of base substitution mutations as a result of two main processes: deamination of methylated cytosines and ultraviolet light–induced mutagenesis

Performance characteristics of next-generation sequencing for the detection of antimicrobial resistance determinants in Escherichia coli genomes and metagenomes

Short-read sequencing can provide detection of multiple genomic determinants of antimicrobial resistance from single bacterial genomes and metagenomic samples. Despite its increasing application in human, animal, and environmental microbiology, including human clinical trials, the performance of short-read Illumina sequencing for antimicrobial resistance gene (ARG) detection, including resistance-conferring single nucleotide polymorphisms (SNPs), has not been systematically characterized. Using paired-end 2 x 150 bp (base pair) Illumina sequencing and an assembly-based method for ARG prediction, we determined sensitivity, positive predictive value (PPV), and sequencing depths required for ARG detection in an Escherichia coli isolate of sequence type (ST) 38 spiked into a synthetic microbial community at varying abundances. Approximately 300,000 reads or 15x genome coverage was sufficient to detect ARGs in E. coli ST38, with comparable sensitivity and PPV to ~100x genome coverage. Using metagenome assembly of mixed microbial communities, ARG detection at E. coli relative abundances of 1% would require assembly of approximately 30 million reads to achieve 15x target coverage. The minimum sequencing depths were validated using public data sets of 948 E. coli genomes and 10 metagenomic rectal swab samples. A read-based approach using k-mer alignment (KMA) for ARG prediction did not substantially improve minimum sequencing depths for ARG detection compared to assembly of the E. coli ST38 genome or the combined metagenomic samples. Analysis of sequencing depths from recent studies assessing ARG content in metagenomic samples demonstrated that sequencing depths had a median estimated detection frequency of 84% (interquartile range: 30%-92%) for a relative abundance of 1%. IMPORTANCE Systematically determining Illumina sequencing performance characteristics for detection of ARGs in metagenomic samples is essential to inform study design and appraisal of human, animal, and environmental metagenomic antimicrobial resistance studies. In this study, we quantified the performance characteristics of ARG detection in E. coli genomes and metagenomes and established a benchmark of ~15x coverage for ARG detection for E. coli in metagenomes. We demonstrate that for low relative abundances, sequencing depths of ~30 million reads or more may be required for adequate sensitivity for many applications

A Randomized Controlled Trial Study of a Multimodal Intervention vs. Cognitive Training to Foster Cognitive and Affective Health in Older Adults.

Research over the past few decades has shown the positive influence that cognitive, social, and physical activities have on older adults' cognitive and affective health. Especially interventions in health-related behaviors, such as cognitive activation, physical activity, social activity, nutrition, mindfulness, and creativity, have shown to be particularly beneficial. Whereas most intervention studies apply unimodal interventions, such as cognitive training (CT), this study investigates the potential to foster cognitive and affective health factors of older adults by means of an autonomy-supportive multimodal intervention (MMI). The intervention integrates everyday life recommendations for six evidence-based areas combined with psychoeducational information. This randomized controlled trial study compares the effects of a MMI and CT on those of a waiting control group (WCG) on cognitive and affective factors, everyday life memory performance, and activity in everyday life. Three groups, including a total of 119 adults aged 65-86 years, attended a 5- or 10-week intervention. Specifically, one group completed a 10-week MMI, the second group completed 5-week of computer-based CT followed by a 5-week MMI, whereas the third group paused before completing the MMI for the last 5 weeks. All participants completed online surveys and cognitive tests at three test points. The findings showed an increase in the number and variability of activities in the everyday lives of all participants. Post hoc analysis on cognitive performance of MMI to CT indicate similar (classic memory and attention) or better (working memory) effects. Furthermore, results on far transfer variables showed interesting trends in favor of the MMI, such as increased well-being and attitude toward the aging brain. Also, the MMI group showed the biggest perceived improvements out of all groups for all self-reported personal variables (memory in everyday life and stress). The results implicate a positive trend toward MMI on cognitive and affective factors of older adults. These tendencies show the potential of a multimodal approach compared to training a specific cognitive function. Moreover, the findings suggest that information about MMI motivates participants to increase activity variability and frequency in everyday life. Finally, the results could also have implications for the primary prevention of neurocognitive deficits and degenerative diseases

Combinatorial activities of SHORT VEGETATIVE PHASE and FLOWERING LOCUS C define distinct modes of flowering regulation in Arabidopsis.

BACKGROUND: The initiation of flowering is an important developmental transition as it marks the beginning of the reproductive phase in plants. The MADS-box transcription factors (TFs) FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE (SVP) form a complex to repress the expression of genes that initiate flowering in Arabidopsis. Both TFs play a central role in the regulatory network by conferring seasonal patterns of flowering. However, their interdependence and biological relevance when acting as a complex have not been extensively studied. RESULTS: We characterized the effects of both TFs individually and as a complex on flowering initiation using transcriptome profiling and DNA-binding occupancy. We find four major clusters regulating transcriptional responses, and that DNA binding scenarios are highly affected by the presence of the cognate partner. Remarkably, we identify genes whose regulation depends exclusively on simultaneous action of both proteins, thus distinguishing between the specificity of the SVP:FLC complex and that of each TF acting individually. The downstream targets of the SVP:FLC complex include a higher proportion of genes regulating floral induction, whereas those bound by either TF independently are biased towards floral development. Many genes involved in gibberellin-related processes are bound by the SVP:FLC complex, suggesting that direct regulation of gibberellin metabolism by FLC and SVP contributes to their effects on flowering. CONCLUSIONS: The regulatory codes controlled by SVP and FLC were deciphered at the genome-wide level revealing substantial flexibility based on dependent and independent DNA binding that may contribute to variation and robustness in the regulation of flowering

Graphs Cannot Be Indexed in Polynomial Time for Sub-quadratic Time String Matching, Unless SETH Fails

The string matching problem on a node-labeled graph G= (V, E) asks whether a given pattern string P has an occurrence in G, in the form of a path whose concatenation of node labels equals P. This is a basic primitive in various problems in bioinformatics, graph databases, or networks, but only recently proven to have a O(|E||P|)-time lower bound, under the Orthogonal Vectors Hypothesis (OVH). We consider here its indexed version, in which we can index the graph in order to support time-efficient string queries. We show that, under OVH, no polynomial-time indexing scheme of the graph can support querying P in time O(| P| + | E| δ| P| β), with either δ< 1 or β< 1. As a side-contribution, we introduce the notion of linear independent-components (lic) reduction, allowing for a simple proof of our result. As another illustration that hardness of indexing follows as a corollary of a lic reduction, we also translate the quadratic conditional lower bound of Backurs and Indyk (STOC 2015) for the problem of matching a query string inside a text, under edit distance. We obtain an analogous tight quadratic lower bound for its indexed version, improving the recent result of Cohen-Addad, Feuilloley and Starikovskaya (SODA 2019), but with a slightly different boundary condition.Peer reviewe

Prevalencia y características de uveítis como manifestación extraarticular en Espondiloartritis Axial

Introducción: la Uveítis Anterior Aguda (UAA) es la manifestación extraarticular más frecuente en la Espondiloartritis axial (EsPax), con una prevalencia global de 32,7%. El objetivo de este estudio fue determinar la prevalencia de UAA en una cohorte Argentina de pacientes con EsPax, describir sus características clínicas, frecuencia de episodios, respuesta al tratamiento y pronóstico a largo plazo, así como su asociación con características generales de la enfermedad