Obstructing Ureteral Calculi and Presumed Infection: Impact of Antimicrobial Duration and Time From Decompression to Stone Treatment in Developing Urosepsis.

OBJECTIVE: To determine whether the duration of antibiotic treatment and timing between urgent renal decompression and stone intervention impacts the risk of developing urosepsis following definitive stone treatment. MATERIALS & METHODS: A retrospective review of patients who were diagnosed with obstructive urolithiasis and underwent urgent decompression with a ureteral double J stent or percutaneous nephrostomy at our institution between 2012 and 2018 was performed. We narrowed our analysis to the subset of patients who had suspected infection and received definitive stone treatment at our institution. Demographic, infection and antimicrobial data, and initial admission to stone treatment characteristics were collected. Factors associated with developing urosepsis were analyzed. RESULTS: We identified 872 patients who were treated with urgent renal decompression, of which 215 were analyzed that had suspected infection and also received definitive stone removal at our institution. Thirty-three had fevers, 64.2% had a positive urine culture, and 45.6% had urosepsis at the initial presentation. The median antibiotics duration post decompression was 13 days (IQR 8-18). The median duration from decompression to stone treatment was 17 days (IQR 12-27). Of all, 4.6% of the patients developed urosepsis post ureteroscopy and 5% post percutaneous nephrolithotomy. No factors were associated with developing urosepsis post stone treatment on logistic regression analyses. CONCLUSION: In patients requiring urgent decompression for obstructing urolithiasis and suspected infection, the time between decompression and stone treatment and the length of antibiotic exposure did not impact rates of postoperative urosepsis. This highlights the importance of maintaining high clinical suspicion for prolonged use of antibiotics, to prevent overtreatment and possible exacerbation of antibiotic resistance.

Genetic Markers of Benzimidazole Resistance among Human Hookworms (Necator americanus) in Kintampo North Municipality, Ghana.

Hookworm infection causes anemia, malnutrition, and growth delay, especially in children living in sub-Saharan Africa. The World Health Organization recommends periodic mass drug administration (MDA) of anthelminthics to school-age children (SAC) as a means of reducing morbidity. Recently, questions have been raised about the effectiveness of MDA as a global control strategy for hookworms and other soil-transmitted helminths (STHs). Genomic DNA was extracted from Necator americanus hookworm eggs isolated from SAC enrolled in a cross-sectional study of STH epidemiology and deworming response in Kintampo North Municipality, Ghana. A polymerase chain reaction (PCR) assay was then used to identify single-nucleotide polymorphisms (SNPs) associated with benzimidazole resistance within the N. americanus ß-tubulin gene. Both F167Y and F200Y resistance-associated SNPs were detected in hookworm samples from infected study subjects. Furthermore, the ratios of resistant to wild-type SNP at these two loci were increased in posttreatment samples from subjects who were not cured by albendazole, suggesting that deworming drug exposure may enrich resistance-associated mutations. A previously unreported association between F200Y and a third resistance-associated SNP, E198A, was identified by sequencing of F200Y amplicons. These data confirm that markers of benzimidazole resistance are circulating among hookworms in central Ghana, with unknown potential to impact the effectiveness and sustainability of chemotherapeutic approaches to disease transmission and control.

Developmental expression patterns of protein kinase A catalytic subunits in zebrafish.

Protein kinase A (PKA), also known as cAMP dependent protein kinase, is an essential component of many signaling pathways, many of which regulate key developmental processes. Inactive PKA is a tetrameric holoenzyme, comprised of two catalytic (PRKAC), and two regulatory subunits. Upon cAMP binding, the catalytic subunits are released and thereby activated. There are multiple isoforms of PKA catalytic subunits, but their individual roles are not well understood. In order to begin studying their roles in zebrafish development, it is first necessary to identify the spatial and temporal expression profiles for each prkac subunit. Here we evaluate the expression profiles for the four zebrafish prkacs: prkacαa, αb, ßa, and ßb, at key developmental time points: 24, 48 and 72 h post fertilization. We show that zebrafish prkacs are expressed throughout the developing nervous system, each showing unique expression patterns. This body of work will inform future functional studies into the roles of PKA during development.