Publications

OBJECTIVES

Despite extensive research into the determinants of electronic nicotine delivery system (ENDS) uptake, few studies have examined the psychosocial benefits ENDS users seek and experience. Using a consumer ritual framework, we explored how ENDS users recreated or replaced smoking practices, and considered implications for smoking cessation.

DESIGN

In-depth interviews; data analysed using thematic analysis.

SETTING

Dunedin, New Zealand.

PARTICIPANTS

16 young adult ENDS users (age M=21.4, SD=1.9; 44% female).

RESULTS

Participants reported using different ENDS to achieve varying outcomes. Some used 'cigalikes' to recreate a physically and visually similar experience to smoking; they privileged device appearance over nicotine delivery. In contrast, others used personally crafted mods to develop new rituals that differentiated them from smokers and showcased their technical expertise. Irrespective of the device they used, several former smokers and dual users of cigarettes and ENDS experienced strong nostalgia for smoking attributes, particularly the elemental appeal of fire and the finiteness of a cigarette. Non-smoking participants used ENDS to maintain social connections with their peers.

CONCLUSIONS

Participants used ENDS to construct rituals that recreated or replaced smoking attributes, and that varied in the emphasis given to device appearance, nicotine delivery, and social performance. Identifying how ENDS users create new rituals and the components they privilege within these could help promote full transition from smoking to ENDS and identify those at greatest risk of dual use or relapse to cigarette smoking.

Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC 32 nM), Ugandan field isolates (mean ex vivo IC 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED 0.34 and 0.57 mg kg, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these mutations in the active site, where AN3661 is predicted to bind. Transcripts for three trophozoite-expressed genes were lost in AN3661-treated trophozoites, which was not observed in parasites selected or engineered for AN3661 resistance. Our results identify the pre-mRNA processing factor PfCPSF3 as a promising antimalarial drug target.

BACKGROUND

Glucocorticoid receptor (GR) activity plays a role in many aspects of human physiology and may play a crucial role in chemotherapy resistance in a wide variety of solid tumors. A novel immunohistochemistry (IHC) based assay has been previously developed and validated in order to assess GR immunoreactivity in triple-negative breast cancer. The current study investigates the standardized use of this validated assay to assess GR expression in a broad range of solid tumor malignancies.

METHODS

Archived formalin-fixed paraffin-embedded tumor bank samples (n=236) from 20 different solid tumor types were analyzed immunohistochemically. Nuclear staining was reported based on the H-score method using differential intensity scores (0, 1+, 2+, or 3+) with the percent stained (out of at least 100 carcinoma cells) recorded at each intensity.

RESULTS

GR was expressed in all tumor types that had been evaluated. Renal cell carcinoma, sarcoma, cervical cancer, and melanoma were those with the highest mean H-scores, indicating high levels of GR expression. Colon, endometrial, and gastric cancers had lower GR staining percentages and intensities, resulting in the lowest mean H-scores.

CONCLUSION

A validated IHC assay revealed GR immunoreactivity in all solid tumor types studied and allowed for standardized comparison of reactivity among the different malignancies.

IMPACT

Baseline expression levels of GR may be a useful biomarker when pharmaceutically targeting GR in research or clinical setting.

BACKGROUND

Considerable racial and ethnic disparities have been identified in maternal and infant health in the United States, and access to postpartum care likely contributes to these disparities. Contraception is an important component of postpartum care that helps women and their families achieve optimal interpregnancy intervals and avoid rapid repeat pregnancies and preterm births. National quality measurements to assess postpartum contraception are being developed and piloted.

OBJECTIVE

To assess racial/ethnic variation in receipt of postpartum care and contraception among low-income women in California.

STUDY DESIGN

We conducted a prospective cohort study of 199,860 Californian women aged 15-44 with a Medicaid-funded delivery in 2012. We examined racial/ethnic variation of postpartum care and contraception using multivariable logistic regression to control for maternal age, language, cesarean delivery, Medicaid program, and residence in a primary care shortage area (PCSA).

RESULTS

Only one-half of mothers attended a postpartum visit (49.4%) or received contraception (47.5%). Compared with white women, black women attended postpartum visits less often (adjusted odds ratio [aOR], 0.73; 95% confidence interval [CI], 0.71-0.76), were less likely to receive any contraception (aOR, 0.83; 95% CI, 0.78-0.89) and were less likely to receive highly effective contraception (aOR, 0.64; 95% CI, 0.58-0.71). Women with Spanish as their primary language were more likely to get any contraception (aOR, 1.15; 95% CI, 1.11-1.19) but had significantly lower odds of receiving a highly effective method (aOR, 0.94; 95% CI, 0.90-0.99) compared with women with English as their primary language. Similarly, women in PCSAs had a greater odds of getting any contraception (aOR, 1.06; 95% CI, 1.03-1.09), but 24% lower odds of getting highly effective contraception than women not living in PCSAs (aOR, 0.76; 95% CI, 0.73-0.79).

CONCLUSION

Significant racial/ethnic disparities exist among low-income Californian mothers' likelihood of attending postpartum visits and receiving postpartum contraception as well as receiving highly effective contraception.