Learning goals are potentially powerful tools to mediate interactions between students, supervisors and patients, and to reconcile contradictions in work-based learning environments. Learning goals provide a means to develop not only learners, but also learning systems.

Objectives: Enterobacter aerogenes was recently renamed Klebsiella aerogenes. This study aimed to identify differences in clinical characteristics, outcomes, and bacterial genetics among patients with K. aerogenes versus Enterobacter species bloodstream infections (BSI). Methods: We prospectively enrolled patients with K. aerogenes or Enterobacter cloacae complex (Ecc) BSI from 2002-2015. We performed whole genome sequencing (WGS) and pan-genome analysis on all bacteria. Results: Overall, 150 patients with K. aerogenes (46/150 [31%]) or Ecc (104/150 [69%]) BSI were enrolled. The two groups had similar baseline characteristics. Neither total in-hospital mortality (13/46 [28%] versus 22/104 [21%]; p=0.3) nor attributable in-hospital mortality (9/46 [20%] versus 13/104 [12%]; p=0.3) differed between patients with K. aerogenes versus Ecc BSI, respectively. However, poor clinical outcome (death before discharge, recurrent BSI, and/or BSI complication) was higher for K. aerogenes than Ecc BSI (32/46 [70%] versus 42/104 [40%]; p=0.001). In a multivariable regression model, K. aerogenes BSI, relative to Ecc BSI, was predictive of poor clinical outcome (odds ratio 3.3; 95% confidence interval 1.4-8.1; p=0.008). Pan-genome analysis revealed 983 genes in 323 genomic islands unique to K. aerogenes isolates, including putative virulence genes involved in iron acquisition (n=67), fimbriae/pili/flagella production (n=117), and metal homeostasis (n=34). Antibiotic resistance was largely found in Ecc lineage 1, which had a higher rate of multidrug resistant phenotype (23/54 [43%]) relative to all other bacterial isolates (23/96 [24%]; p=0.03). Conclusions: K. aerogenes BSI was associated with poor clinical outcomes relative to Ecc BSI. Putative virulence factors in K. aerogenes may account for these differences.

Background In sub-Saharan Africa couple HIV testing and counseling (CHTC) has been associated with substantial increases in safe sex, especially when at least one partner is HIV-infected. However, this relationship has not been characterized in an Option B+ context. Setting The study was conducted at the antenatal clinic at Bwaila District Hospital in Lilongwe, Malawi in 2016 under an Option B+ program. Methods Ninety heterosexual couples with an HIV-infected pregnant woman (female-positive couples) and 47 couples with an HIV-uninfected pregnant woman (female-negative couples) were enrolled in an observational study. Each couple member was assessed immediately before and one month after CHTC for safe sex (abstinence or consistent condom use in the last month). Generalized estimating equations were used to model change in safe sex before and after CHTC and to compare safe sex between female-positive and female-negative couples. Results Mean age was 26 years among women and 32 years among men. Before CHTC, safe sex was comparable among female-positive couples (8%) and female-negative couples (2%) (RR: 3.7, 95% CI: 0.5, 29.8). One month after CHTC, safe sex was higher among female-positive couples (75%) than among female-negative couples (3%) (RR: 30.0, 95% CI: 4.3, 207.7). Safe sex increased substantially after CTHC for female-positive couples (RR 9.6, 95% CI: 4.6, 20.0), but not for female-negative couples (RR: 1.2, 95% CI: 0.1, 18.7). Conclusion Engaging pregnant couples in CHTC can have prevention benefits for couples with an HIV-infected pregnant woman, but additional prevention approaches may be needed for couples with an HIV-uninfected pregnant woman.

Trex2 is a 39 / 59 exonuclease that removes 39-mismatched sequences in a biochemical assay; however, its biological function remains unclear. To address biology we previously generated trex2 null mouse embryonic stem (ES) cells and expressed in these cells wild-type human TREX2 cDNA (Trex2 hTX2 ) or cDNA with a single-amino-acid change in the catalytic domain (Trex2 H188A ) or in the DNA-binding domain (Trex2 R167A ). We found the trex2 null and Trex2 H188A cells exhibited spontaneous broken chromosomes and trex2 null cells exhibited spontaneous chromosomal rearrangements. We also found ectopically expressed human TREX2 was active at the 39 ends of I-SceI-induced chromosomal double-strand breaks (DSBs). Therefore, we hypothesized Trex2 participates in DNA DSB repair by modifying 39 ends. This may be especially important for ends with damaged nucleotides. Here we present data that are unexpected and prompt a new model. We found Trex2-altered cells (null, H188A, and R167A) were not hypersensitive to camptothecin, a type-1 topoisomerase inhibitor that induces DSBs at replication forks. In addition, Trex2-altered cells were not hypersensitive to g-radiation, an agent that causes DSBs throughout the cell cycle. This observation held true even in cells compromised for one of the two major DSB repair pathways: homology-directed repair (HDR) or nonhomologous end joining (NHEJ). Trex2 deletion also enhanced repair of an I-SceI-induced DSB by both HDR and NHEJ without affecting pathway choice. Interestingly, however, trex2 null cells exhibited reduced spontaneous sister chromatid exchanges (SCEs) but this was not due to a defect in HDR-mediated crossing over. Therefore, reduced spontaneous SCE could be a manifestation of the same defect that caused spontaneous broken chromosomes and spontaneous chromosomal rearrangements. These unexpected data suggest Trex2 does not enable DSB repair and prompt a new model that posits Trex2 suppresses the formation of broken chromosomes.

Malawi's Option B+ program provides all HIV-infected pregnant women free lifelong antiretroviral therapy (ART), but challenges remain regarding retention and ART adherence, potentially due to male partner barriers. We explored relationships between male partner involvement and Option B+ retention and adherence. In 2014, a randomized controlled trial in Malawi compared male recruitment strategies for couple HIV testing and counseling (cHTC) at an antenatal clinic. This secondary analysis was conducted among the entire cohort (N = 200) of women, irrespective of randomization status. We assessed whether cHTC attendance, early disclosure of HIV-positive status, and partner ART reminders were associated with retention and adherence at one month after starting treatment. Retention was defined as attending HIV clinic follow-up within one day of running out of pills. Adherence was defined as taking ≥95% of ARTs by pill count. We used binomial regression to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Median female age was 26 years. Most women (79%) were retained; of these, 68% were adherent. Receiving cHTC was associated with improved retention (aRR 1.33, 95% CI 1.12, 1.59). Receiving male partner ART reminders was weakly associated with retention (aRR 1.16, 95% CI 0.96, 1.39). Disclosure within one day was not associated with retention (aRR 1.08, 95% CI: 0.91, 1.28). Among those who were retained, these three behaviors were not associated with improved 95% adherence. CHTC could play an important role in improving Option B+ retention. Increasing cHTC participation and enhancing adherence-related messages within cHTC are important.