Genetic Variability of HIV-1 for Drug Resistance Assay Development
2016; 8 (2)
Genetic Variability of HIV-1 for Drug Resistance Assay Development.
2016; 8 (2)
Fidaxomicin versus Conventional Antimicrobial Therapy in 59 Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation with Clostridium difficile-Associated Diarrhea
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
2013; 57 (9): 4501-4505
A hybridization-based point-of-care (POC) assay for HIV-1 drug resistance would be useful in low- and middle-income countries (LMICs) where resistance testing is not routinely available. The major obstacle in developing such an assay is the extreme genetic variability of HIV-1. We analyzed 27,203 reverse transcriptase (RT) sequences from the Stanford HIV Drug Resistance Database originating from six LMIC regions. We characterized the variability in a 27-nucleotide window surrounding six clinically important drug resistance mutations (DRMs) at positions 65, 103, 106, 181, 184, and 190. The number of distinct codons at each DRM position ranged from four at position 184 to 11 at position 190. Depending on the mutation, between 11 and 15 of the 24 flanking nucleotide positions were variable. Nonetheless, most flanking sequences differed from a core set of 10 flanking sequences by just one or two nucleotides. Flanking sequence variability was also lower in each LMIC region compared with overall variability in all regions. We also describe an online program that we developed to perform similar analyses for mutations at any position in RT, protease, or integrase.
View details for DOI 10.3390/v8020048
View details for PubMedID 26875985
Investigation of a novel, heritable bleeding diathesis of thoroughbred horses and development of a screening assay
JOURNAL OF VETERINARY INTERNAL MEDICINE
2006; 20 (6): 1450-1456
The feasibility of fidaxomicin versus vancomycin and metronidazole (conventional therapy) was assessed in 59 transplant recipients with 61 episodes of Clostridium difficile-associated diarrhea (CDAD). Overall clinical cure was achieved in 86% of episodes, and in 7% of episodes, infection recurred. Fidaxomicin was well tolerated. Clinical cures were not significantly different compared with conventional therapy (67% versus 89%, respectively; P = 0.06). Univariate analysis of predictors for lack of clinical cure included continued use of broad-spectrum systemic antibiotics (P = 0.026) and prior diagnosis of CDAD (95% confidence interval, 1.113 to 19.569; odds ratio, 4.667; P = 0.041). New-onset vancomycin-resistant Enterococcus (VRE) colonization was not noted after fidaxomicin therapy alone. However, this occurred in 10 of 28 patients (36%) following conventional therapy, and 2 of 3 patients with subsequent bacteremia died.
View details for DOI 10.1128/AAC.01120-13
View details for Web of Science ID 000323285500052
View details for PubMedID 23836168
Bleeding in racing horses associated with exercise appears to be multifactorial, and clinical investigation into severe cases rarely occurs. Previously, we reported a severe bleeding diathesis in a Thoroughbred mare. Herein, we describe the cellular physiology of this defect, provide a diagnostic tool for identifying it, and demonstrate that the dysfunction is heritable.The subject has a heritable defect in platelet secretion that reduces thrombin generation in the absence of additional plasma factors and delays the onset of thrombin production even in the presence of these factors.The study included 3 clinically normal Thoroughbred horses: the subject and her offspring.Washed platelets were examined for their ability to (1) translocate phosphatidylserine to the outer leaflet of the platelet membrane as determined by annexin-V binding, (2) generate thrombin as assessed by the activity of the prothrombinase enzyme complex, and (3) bind fibrinogen and form aggregates as determined by flow cytometry.Subject and offspring platelets created procoagulant surfaces by translocating phosphatidylserine. The subject's platelets demonstrated reduced prothrombinase activity, resulting in decreased production of thrombin relative to control platelets. Subject and offspring platelets bound less fibrinogen than control platelets when stimulated with thrombin.The subject mare has a transmissible defect that involves reduced generation of thrombin by activated platelets, resulting in decreased aggregation and ineffective clotting. A flow cytometric assay of fibrinogen binding to washed platelets discriminates individuals with this platelet dysfunction and may be useful for discerning subclinical congenital or acquired platelet dysfunctions.
View details for Web of Science ID 000242567200028
View details for PubMedID 17186864