Mutations in two amino-acid positions were significantly more common in AIDS patients with PCP who failed sulfa/sulfone prophylaxis. These amino acids appeared to be directly involved in both substrate and sulfa binding, based on homology to the Escherichia coli DHPS crystal structure. Thus, the results were consistent with the possibility that mutations in the P. carinii DHPS are responsible for some of the failures of sulfa/sulfone prophylaxis in AIDS patients.

DPP-4 inhibition promotes a distal tubular natriuresis in conjunction with increased levels of intact SDF-1α. Because of the distal location of the natriuretic effect, DPP-4 inhibition does not affect tubuloglomerular feedback or impair renal hemodynamic function, findings relevant to using DPP-4 inhibitors for treating type 2 diabetes.

Key Points Question What are the associations of the COVID-19 pandemic with career development and what are the work culture and childcare needs of employees and trainees? Findings In this survey study, most participants with children did not have childcare fully available and many considered leaving the workforce and were worried about their career. Being female with children or having a clinical job role was associated with consideration for leaving the workforce and reducing hours. Meaning These findings suggest that a substantial number of employees and trainees experienced major stress and work disruptions because of the COVID-19 pandemic.

Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients ( = 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions ( = 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (R), and glomerular hydrostatic pressure (P). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg, = 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in R P, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal R responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.