Investigation of altering single-nucleotide polymorphism density on the power to detect trait loci and frequency of false positive in nonparametric linkage analyses of qualitative traits

Genome-wide linkage analysis using microsatellite markers has been successful in the identification of numerous Mendelian and complex disease loci. The recent availability of high-density single-nucleotide polymorphism (SNP) maps provides a potentially more powerful option. Using the simulated and Collaborative Study on the Genetics of Alcoholism (COGA) datasets from the Genetics Analysis Workshop 14 (GAW14), we examined how altering the density of SNP marker sets impacted the overall information content, the power to detect trait loci, and the number of false positive results. For the simulated data we used SNP maps with density of 0.3 cM, 1 cM, 2 cM, and 3 cM. For the COGA data we combined the marker sets from Illumina and Affymetrix to create a map with average density of 0.25 cM and then, using a sub-sample of these markers, created maps with density of 0.3 cM, 0.6 cM, 1 cM, 2 cM, and 3 cM. For each marker set, multipoint linkage analysis using MERLIN was performed for both dominant and recessive traits derived from marker loci. Our results showed that information content increased with increased map density. For the homogeneous, completely penetrant traits we created, there was only a modest difference in ability to detect trait loci. Additionally, as map density increased there was only a slight increase in the number of false positive results when there was linkage disequilibrium (LD) between markers. The presence of LD between markers may have led to an increased number of false positive regions but no clear relationship between regions of high LD and locations of false positive linkage signals was observed

Modular Synthesis of Semiconducting Graft Co-polymers to Achieve "clickable" Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Semiconducting polymer nanoparticles (SPNs) have been explored for applications in cancer theranostics because of their high absorption coefficients, photostability and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, we describe a method for achieving colloidally stable and low-fouling SPNs by grafting PEG onto the backbone of the fluorescent semiconducting polymer, poly(9,9'-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole) (F8BT-F), in a simple one-step substitution reaction, post-polymerisation. Further, by utilising azide-functionalised PEG we site-specifically "click" anti-HER2 antibodies, Fab fragments, or affibodies onto the SPN surface, which allows the functionalised SPNs to specifically target HER2-positive cancer cells. In vivo, our PEGylated SPNs were found to have excellent circulation efficiencies in zebrafish embryos for up to seven days post-injection. SPNs functionalised with affibodies were then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics. This article is protected by copyright. All rights reserved

Cutaneous alternariosis in a renal transplant patient successfully treated with posaconazole: Case report and literature review

Cutaneous alternariosis is an uncommon fungal infection that most commonly presents in organ transplant patients on immunosuppressive therapy. There are no clinical trials or guidelines to guide treatment of this condition, however itraconazole is the most commonly used antifungal in published cases. Here we report on a case of cutaneous alternariosis in a renal transplant recipient treated with a newer antifungal, posaconazole. A review of published reports of cutaneous alternariosis since 2008 is also discussed

Efficacy of Prompt Initiation of Antiretroviral Therapy in the Treatment of Hemophagocytic Lymphohistiocytosis Triggered by Uncontrolled Human Immunodeficiency Virus

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, rapidly progressive hematologic disorder involving uncontrolled immune system activation. HLH has been associated with viral infections, including human immunodeficiency virus (HIV) infections. We report a case of a critically ill 30-year-old female who was hospitalized with HIV-associated HLH, with a CD4 count of 4 cells/mL and HIV viral load of 1,842,730 copies/mL. After ruling out other potential infectious causes of HLH, antiretroviral therapy (ART) was initiated with darunavir, ritonavir, tenofovir, and emtricitabine. Within one week of initiation of ART, the patient began to improve clinically and hematologically and was stable enough for discharge from the hospital three weeks after starting therapy. This case suggests that treatment with ART in patients with HIV-associated HLH should be considered even in critically ill patients with low CD4 counts

Pulmonary infection with : A case report

Mycobacterium szulgai is a non-tuberculous mycobacterium that is an uncommon cause of infection in humans. Risk factors for infection include immunosuppression and pre-existing lung pathology. Herein, we present a case of a 42-year-old male with chronic obstructive pulmonary disease with pulmonary infection caused by M. szulgai that was successfully treated with a regimen of rifampin, isoniazid, pyrazinamide and ethambutol for 2 months, followed by rifampin, isoniazid and azithromycin for an additional 8 months. Symptomatic and radiographic resolutions were achieved

Effectiveness and safety of nitrofurantoin in outpatient male veterans

Objectives: The aim of the study was to assess both the safety and the effectiveness of nitrofurantoin in male veterans treated for urinary tract infections (UTIs) with varying degrees of renal impairment in the outpatient setting. Nitrofurantoin is an important oral option for treating UTIs given increasing resistance to commonly used agents. Nitrofurantoin is currently contraindicated in patients with a creatinine clearance (CrCl) of < 60 ml/min, but the reason for this threshold has not been well documented. Methods: Data were collected through a retrospective chart review from January 2004 to July 2013 of men who had received nitrofurantoin. Bivariate analyses followed by multivariate analyses were performed between patients experiencing clinical cure and those who did not, to determine factors significantly impacting effectiveness. Results: The Gram stain of the organism causing the UTI and CrCl were significant factors impacting effectiveness. For every 1 ml/min increase in CrCl, the odds of clinical cure increased by 1.3%. Patients with Gram-negative UTIs predictably had 80% cure rates with CrCl around 60 ml/min. Patients with Gram-positive UTIs required higher CrCl, nearing 100 ml/min, to establish an 80% cure rate. Adverse effects did not vary with CrCl. Conclusions: The odds of clinical cure varied with CrCl and with the type of organism causing the UTI, while adverse events did not differ based on renal function. A minimum CrCl of 60 ml/min is suggested for men to achieve an 80% cure rate for UTIs with the most common urinary pathogens

Correlation of BK Virus Neutralizing Serostatus with the Incidence of BK Viremia in Kidney Transplant Recipients

Background: BK virus-associated nephropathy (BKVAN) is the second leading cause of graft loss in kidney transplant recipients. Due to the high prevalence of persistent infection with BK virus (BKV) in the general population, it is possible that either the transplant recipient or donor may act as the source of virus resulting in viruria and viremia. While several studies suggest a correlation between donor-recipient serostatus and the development of BK viremia, specific risk factors for BKV-related complications in the transplant setting remain to be established. Methods: We retrospectively determined the pre-transplant BKV neutralizing serostatus of 116 donor (D)-recipient (R) pairs using infectious BKV neutralization assays with representatives from the four major viral serotypes. The neutralizing serostatus of donors and recipients was then correlated with the incidence of BK viremia during the first year post-transplantation. Results: There were no significant differences in baseline demographics or transplant data among the four neutralizing serostatus groups, with the exception of calculated panel reactive antibody (cPRA) which was lowest in the D+/R- group. Recipients of kidneys from donors with significant serum neutralizing activity (D+) had elevated risk for BK viremia, regardless of recipient serostatus (D+ versus D-: OR 5.0 [CI 1.9-12.7]; P=0.0008). Furthermore, donor-recipient pairs with D+/R- neutralizing serostatus had the greatest risk for BK viremia (OR 4.9 [CI 1.7-14.6]; P=0.004)

Cultural competency of a mobile, customized patient education tool for improving potential kidney transplant recipients' knowledge and decision-making.

Patients considering renal transplantation face an increasingly complex array of choices as a result of the revised kidney transplant allocation system. Decision aids have been shown to improve patient decision-making through the provision of detailed, relevant, individualized clinical data. A mobile iOS-based application (app) including animated patient education and individualized risk-adjusted outcomes following kidney transplants with varying donor characteristics and DSA waiting times was piloted in two large US transplant programs with a diverse group of renal transplant candidates (N = 81). The majority (86%) of patients felt that the app improved their knowledge and was culturally appropriate for their race/ethnicity (67%-85%). Patients scored significantly higher on transplant knowledge testing (9.1/20 to 13.8/20, P &lt; .001) after viewing the app, including patients with low health literacy (8.0 to 13.0, P &lt; .001). Overall knowledge of and interest in living and deceased donor kidney transplantation increased. This pilot project confirmed the benefit and cultural acceptability of this educational tool, and further refinement will explore how to better communicate the risks and benefits of nonstandard donors