30 research outputs found
Randomized Trials to Optimize Treatment of Multidrug-Resistant Tuberculosis: The time for action is now
The time is now right for randomized trials of MDR-TB, say the authors, as the expansion of MDR-TB programs provides the setting in which trials can be implemented
In praise of arrays
Microarray technologies have both fascinated and frustrated the transplant community since their introduction roughly a decade ago. Fascination arose from the possibility offered by the technology to gain a profound insight into the cellular response to immunogenic injury and the potential that this genomic signature would be indicative of the biological mechanism by which that stress was induced. Frustrations have arisen primarily from technical factors such as data variance, the requirement for the application of advanced statistical and mathematical analyses, and difficulties associated with actually recognizing signature gene-expression patterns and discerning mechanisms. To aid the understanding of this powerful tool, its versatility, and how it is dramatically changing the molecular approach to biomedical and clinical research, this teaching review describes the technology and its applications, as well as the limitations and evolution of microarrays, in the field of organ transplantation. Finally, it calls upon the attention of the transplant community to integrate into multidisciplinary teams, to take advantage of this technology and its expanding applications in unraveling the complex injury circuits that currently limit transplant survival
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
Evaluation of a Sequential Antibiotic Treatment Regimen of Ampicillin, Ciprofloxacin and Fosfomycin against Escherichia coli CFT073 in the Hollow Fiber Infection Model Compared with Simultaneous Combination Treatment
Objective: Employ the hollow fiber infection model (HFIM) to study sequential antibiotic administration (ampicillin, ciprofloxacin and fosfomycin) using human pharmacokinetic profiles to measure changes in the rate of antibiotic resistance development and compare this to simultaneous combination therapy with the same antibiotic combinations. Methods: Escherichia coli CFT073, a clinical uropathogenic strain, was exposed individually to clinically relevant pharmacokinetic concentrations of ampicillin on day 1, ciprofloxacin on day 2 and fosfomycin on day 3. This sequence was continued for 10 days in the HFIM. Bacterial samples were collected at different time points to enumerate total and resistant bacterial populations. The results were compared with the simultaneous combination therapy previously studied. Results: Sequential antibiotic treatment (ampicillin-ciprofloxacin-fosfomycin sequence) resulted in the early emergence of single and multi-antibiotic-resistant subpopulations, while the simultaneous treatment regimen significantly delayed or prevented the emergence of resistant subpopulations. Conclusion: Sequential administration of these antibiotic monotherapies did not significantly delay the emergence of resistant subpopulations compared to simultaneous treatment with combinations of the same antibiotics. Further studies are warranted to evaluate different sequences of the same antibiotics in delaying emergent resistance
Concordant mitochondrial and microsatellite DNA structuring between Polish lowland and Carpathian Mountain wolves
Phylogeographic studies of highly mobile large carnivores suggest that intra-specific genetic differentiation of modern species might be the consequence of the most recent Pleistocene glaciation. However, the relative influence of biogeographical processes and subsequent human-induced population fragmentation requires a better understanding. Poland represents the western edge of relatively continuous distributions of many wide-ranging species, e.g. lynx (Lynx lynx), wolves (Canis lupus), moose (Alces alces) and, therefore, a key area for understanding historic and contemporary patterns of gene flow in central Europe. We examined wolf genetic structure in Poland and in a recently recolonized area in eastern Germany using microsatellite profiles (n = 457) and mitochondrial DNA sequencing (mtDNA, n = 333) from faecal samples. We found significant genetic structure and high levels of differentiation between wolves in the Carpathian Mountains and the Polish lowlands. Our findings are consistent with previously reported mtDNA subdivision between northern lowlands and southern mountains, and add new and concordant findings based on autosomal marker variation. Wolves in western Poland and eastern Germany showed limited differentiation from northeastern Poland. Although the presence of private alleles suggests immigration also from areas not sampled in this study, most individuals seem to be immigrants from northeastern Poland or their descendants. We observed moderate genetic differentiation between certain northeastern lowland regions separated by less than 50 km. Moreover, mtDNA results indicated a southeastern subpopulation near the border with Ukraine. The observed structure might reflect landscape fragmentation and/or ecological differences resulting in natal habitat-biased dispersal