Transcriptome sequences of the grape powdery mildew fungus Erysiphe necator were used to develop microsatellite markers (EST‐SSRs) to study its relatively unexplored population structure in its centre of diversity in eastern North America. Screening the transcriptome sequences revealed 116 contigs with candidate microsatellites, from which 11 polymorphic microsatellite markers were developed from 31 markers tested. Eight of these markers were used to genotype isolates from different regions and hosts in the eastern USA and compare them to samples from southern France and Italy. Genetic diversity in the eastern USA is much greater than in Europe. Bayesian cluster analyses showed that 10 isolates from North America have high affinities with, but differ from, European group A; these are referred to as A‐like isolates. No isolates with close affinity to European group B were found in the eastern USA. Bayesian analyses also detected genetic differentiation between isolates from Vitis rotundifolia and isolates from other Vitis hosts. Genetic differentiation detected between the northeastern and southeastern USA was mostly attributable to the A‐like isolates in the southeast, which are significantly more aggressive than the other populations. This research demonstrates that transcriptome sequencing of fungal pathogens is useful for developing genetic markers in protein‐coding regions and highlights the role of these markers in population biology studies of E. necator.

Objective: To review glucose-lowering efficacy and changes in renal function associated with GLP-1 receptor agonists and SGLT2-Inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Data Sources: A literature search of MEDLINE and Cochrane databases was performed from 2000 to March 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, glucagon-like peptide-1 receptor agonists, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and chronic kidney disease. References of identified articles were also reviewed. Study Selection and Data Extraction: English-language studies investigating glucose-lowering endpoints and/or changes in renal function with a U.S. approved SGLT2 inhibitor or GLP-1 receptor agonist were included. Data Synthesis: GLP-1 agonists and SGLT2-Inhibitors effectively lower glucose in patients with T2DM and CKD. Both agents have demonstrated short-term renoprotective effects by slowing progression of albuminuria and decreasing urine albumin-to-creatinine values. Relevance to Patient Care and Clinical Practice: This review highlights the glucose-lowering efficacy and reported renal benefits of GLP-1 agonists and SGLT2-Inhibitors when used in patients with T2DM and CKD. Given that these comorbidities are associated with increased cardiovascular risk, we believe that these agents should be the preferred add-on agents in most patients with uncontrolled T2DM and CKD. Conclusions: In patients with T2DM and CKD, GLP-1 agonists and SGLT2-Inhibitors are effective in lowering glucose, preventing progression of worsening albuminuria, and may reverse the

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Six studies (4 administering droxidopa and 2 administering midodrine) enrolling a total of 783 patients were included for analysis. The mean change from baseline in sSBP was significantly greater for both drugs when compared with placebo (droxidopa 6.2 mm Hg [95% CrI = 2.4-10] and midodrine 17 mm Hg [95% CrI = 11.4-23]). Comparative analysis revealed a significant credible difference between droxidopa and midodrine. The RR for supine hypertension was significantly greater for midodrine, but not droxidopa, when compared with placebo (droxidopa RR = 1.4 [95% CrI = 0.7-2.7] and midodrine RR = 5.1 [95% CrI = 1.6-24]). Conclusion and Relevance: In patients with NOH, both droxidopa and midodrine significantly increase sSBP, the latter to a greater extent. However, midodrine, but not droxidopa, significantly increases risk of supine hypertension.

Increasingly older adults are traveling to international destinations with malaria as a present risk. Surveillance systems indicate that older adults are more likely to suffer severe complications from malaria. The role of health care providers in selecting an appropriate medication for chemoprophylaxis or treatment of malaria in adults becomes more difficult as older adults undergo physiologic changes that alter the pharmacokinetic and pharmacodynamic nature of medications potentially causing increased drug interactions, adverse events and altered drug action. A comprehensive literature search from 1970 to present, with a focus on the past 10 years, was conducted on drug interactions, pharmacokinetic and pharmacodynamic effects on antimalarials in adults. It was determined that due to pharmacodynamic and pharmacokinetic changes in older adults, especially renal and cardiovascular, special attention should be given to this population of travelers in order to minimize the likelihood of adverse events or altered drug efficacy. Antimalarial drug–disease interactions in older adults can occur more often due to QT prolongation, exacerbation of hypoglycemia, decreased renal elimination and decreased hepatic metabolism. Older antimalarials have well-documented drug–drug interactions. Tafenoquine, a new antimalarial, requires glucose-6-phosphate dehydrogenase screening like primaquine and monitoring of new potential drug interaction with MATE1 and OCT2 substrates. While drug–drug interactions in older travelers may occur more often as a result of polypharmacy, data did not indicate adverse reactions or decreased drug efficacy is greater compared with younger adults. Overall, with the exception of recently approved tafenoquine, much is known about antimalarial drug and disease interactions, but new drugs are always being approved, requiring travel health providers to understand the pharmacokinetics and pharmacodynamics of antimalarial drugs to predict the impact on safety and efficacy in travelers. This guide provides travel health providers with valuable insights on potential outcomes associated with drug interactions in adults and recommended monitoring or drug regimen modification.