Treating hemodialysis access thrombosis with the InThrill Thrombectomy System: Technique and case report.

The purpose of this report is to describe via a case example an efficient mechanical thrombectomy technique for hemodialysis access thrombosis using the InThrill Thrombectomy System (Inari Medical, Irvine, CA). A man in his late 60s with end-stage renal disease and a thrombosed femoral arteriovenous graft (AVG) underwent a thrombectomy procedure to remove all thrombotic material including the arterial plug and restore use of the graft for hemodialysis. The InThrill Thrombectomy System used in this procedure consists of a mechanical thrombectomy catheter with a wall-apposing coring element and a sheath with a retractable funnel and aspiration port. The technique starts with gaining wire and sheath access towards the venous outflow. The InThrill Thrombectomy catheter is deployed proximal to the sheath to sequentially remove small segments of thrombus thus avoiding sheath obstruction. A locking syringe is used for rapid aspiration, reducing or eliminating the need to remove the InThrill sheath with every mechanical thrombectomy pass. Finally, the arterial plug is pulled using a Fogarty balloon sheath (Edwards Lifesciences, Irvine, CA) and extracted using the InThrill catheter, removing what may be the nidus for recurrent AV access thrombosis. The technique described here provided a means to remove all thrombotic material including the arterial plug in a planned, sequential manner, without the need for thrombolytics. Patency was restored to the patient's femoral AVG within 60 minutes, and hemodialysis resumed shortly thereafter. Further studies are needed to support long-term efficacy of this thrombolytic-free treatment option.

Aptamers and the RNA world, past and present.

Aptamers and the SELEX process were discovered over two decades ago. These discoveries have spawned a productive academic and commercial industry. The collective results provide insights into biology, past and present, through an in vitro evolutionary exploration of the nature of nucleic acids and their potential roles in ancient life. Aptamers have helped usher in an RNA renaissance. Here we explore some of the evolution of the aptamer field and the insights it has provided for conceptualizing an RNA world, from its nascence to our current endeavor employing aptamers in human proteomics to discover biomarkers of health and disease.

Expanding the chemistry of DNA for in vitro selection.

Six new 5-position modified dUTP derivatives connected by a unique amide linkage were synthesized and tested for compatibility with the enzymatic steps of in vitro selection. Six commercially available DNA polymerases were tested for their ability to efficiently incorporate each of these dUTP derivatives during PCR. It was not possible to perform PCR under standard conditions using any of the modified dUTP derivatives studied. In contrast, primer extension reactions of random templates, as well as defined sequence templates, were successful. KOD XL and D. Vent DNA polymerases were found to be the most efficient at synthesizing full-length primer extension product, with all of the dUTP derivatives tested giving yields similar to those obtained with TTP. Several of these modified dUTPs were then used in an in vitro selection experiment comparing the use of modified dUTP derivatives with TTP for selecting aptamers to a protein target (necrosis factor receptor superfamily member 9, TNFRSF9) that had previously been found to be refractory to in vitro selection using DNA. Remarkably, selections employing modified DNA libraries resulted in the first successful isolation of DNA aptamers able to bind TNFRSF9 with high affinity.

Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci.

BACKGROUND: Genome-wide linkage scans to identify asthma susceptibility loci have revealed many linked regions, including a broad region on chromosome 5p. OBJECTIVE: To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR) locus. METHODS: We performed fine mapping and positional candidate studies of this region in the Hutterites and an outbred case-control sample from Germany by genotyping 89 single nucleotide polymorphisms (SNPs) in 22 genes. SNP and haplotype analyses were performed. RESULTS: Three genes in a distal region (zinc finger RNA binding protein [ZFR], natriuretic peptide receptor C, and a disintegrin and metalloproteinase domain with thrombospondin type 1 motif [ADAMTS12]) were associated with BHR, whereas 4 genes in a proximal region (prolactin receptor, IL-7 receptor [IL7R], leukemia inhibitory factor receptor [LIFR], and prostaglandin E4 receptor [PTGER4]) were associated with asthma symptoms in the Hutterites. Furthermore, nearly the entire original linkage signal in the Hutterites was generated by individuals who had the risk-associated alleles in ZFR3, natriuretic peptide receptor C, ADAMTS12, LIFR, and PTGER4. Variation in ADAMTS12, IL7R, and PTGER4 were also associated with asthma in the outbred Germans, and the frequencies of long-range haplotypes composed of SNPs at ZFR, ADAMTS12, IL7R, LIFR, and PTGER4 were significantly different between both the German and Hutterite cases and controls. There is little linkage disequilbrium between alleles in these 2 regions in either population. CONCLUSION: These results suggest that a broad region on 5p, separated by >9 Mb, harbors at least 2 and possibly 5 asthma or BHR susceptibility loci. These findings are consistent with the hypothesis that regions providing evidence for linkage in multiple populations may, in fact, house more than 1 susceptibility locus, as appears to be the case for the linked region on 5p. CLINICAL IMPLICATIONS: Identifying asthma or BHR genes could lead to novel therapeutic approaches.

Photoaptamer arrays applied to multiplexed proteomic analysis.

Multiplexed photoaptamer-based arrays that allow for the simultaneous measurement of multiple proteins of interest in serum samples are described. Since photoaptamers covalently bind to their target analytes before fluorescent signal detection, the arrays can be vigorously washed to remove background proteins, providing the potential for superior signal-to-noise ratios and lower limits of quantification in biological matrices. Data are presented here for a 17-plex photoaptamer array exhibiting limits of detection below 10 fM for several analytes including interleukin-16, vascular endothelial growth factor, and endostatin and able to measure proteins in 10% serum samples. The assays are simple, scalable, and reproducible. Affinity of the capture reagent is shown to be directly correlated to the limit of detection for the analyte on the array.

Deposições irregulares de resíduos da construçäo civil na cidade de Säo Paulo / Unregulated dumping of waste from civil construction and demolition in the city of Säo Paulo

Objetivo. Investigar possíveis causas da persistência da deposiçäo irregular de Resíduos da Construçäo Civil - RCD em vias e logradouros públicos da cidade de Säo Paulo, de forma a gerar subsídios para a implementaçäo de políticas públicas relacionadas à limpeza urbana municipal, com a finalidade de contribuir para a melhoria da saúde e qualidade de vida no município de Säo Paulo. Métodos. Para a identificaçäo das causas sociais perguntou-se que categorias de participantes estäo envolvidos com as deposições irregulares de RCD, quais as expectativas de umas em relaçäo às outras e que sanções existem para cada categoria de participantes utilizar em suas tentativas de controlar o comportamento de outras categorias envolvidas. Conclusões. As possíveis causas da persistência da deposiçäo irregular de RCD em áreas de domínio público da cidade de Säo Paulo estäo relacionadas à inexistência de política pública municipal que considere os problemas dos RCD; ao investimento de recursos significativos quase que exclusivamente na contínua remoçäo dos RCD; à inexpressividade e à näo efetividade de ações de controle das deposições irregulares em vias e logradouros públicos por parte da administraçäo municipal; à distância de transporte entre a geraçäo e a destinaçäo de RCD como fator limitante para a correta deposiçäo desses resíduos; à substancial economia obtida na externalizaçäo para a cidade dos custos de transporte e deposiçäo pelos transportadores privados; à contrataçäo de transportadores privados irregulares pelos geradores de resíduos da construçäo civil; ao recebimento de valores significativos por empresas contratadas pela administraçäo municipal como pagamento por serviços de remoçäo, remunerados por quantidade de RCD removida.