Background: Maternal smoking during pregnancy remains a public health concern in the United States (US). We examined whether the prevalence of smoking during pregnancy decreased between 2010 and 2017 and how trends differed by demographic subgroups. Methods: We used 2010-2017 data from the National Center for Health Statistics. Rao-Scott Chi-Square tests were performed to compare characteristics between smoking and nonsmoking groups. Cochran-Armitage tests and logistic regression were used to assess overall changes in the prevalence of smoking during pregnancy over time and changes for age, race, and educational attainment subgroups. Results: The prevalence of smoking during pregnancy decreased from 9.2% in 2010 to 6.9% in 2017. In 2017, the prevalence was highest among women aged 20-24 (9.9%), American Indian/Alaskan Natives (15%), and those with a high school diploma or General Educational Development (GED) (12.2%). The prevalence was lowest among women younger than 15 (1.7%), Asian/Pacific Islanders (1%), and those who had a master's degree and higher (0.3%). Prevalence did not decrease significantly over time in the 35-39 age group (4.5 to 4.4%; p = 0.08), and increased dramatically for women with less than a high school diploma from 10.2 to 11.8%; p < 0.0001. Conclusions: Smoking prevalence during pregnancy in the US is declining, but is highest among younger women (20-24), American Indian/Alaska Natives, and women with a high school diploma or GED. In addition, the prevalence has increased for women with the least education. Targeted research and tobacco control interventions could help address the specific needs of these high-risk subpopulations.

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Electronic cigarettes (e-cigarette) use is rapidly increasing in the U.S., especially among adolescents. A significant number of adolescents use both cigarettes and e-cigarettes, often referred to as dual use. We used a new classification of dual use, taking into account the frequency of use of both products. In addition, we examined the association between dual use with time to first cigarette after waking (a nicotine dependence measure) and quit intention. Methods: Data were drawn from the 2015e2018 National Youth Tobacco Survey. We grouped participants by dual use frequency. Multivariable logistic regression was used to examine the association of dual use frequency with nicotine dependence and quit intention. Results: Different categories of dual users varied in demographic characteristics and beliefs on the harms of cigarette smoking and e-cigarette use. Compared with cigarette-only smokers, significantly higher odds of nicotine dependence were found for high-frequency e-cigarette dual users (within 5 minutes of awakening, odds ratio [OR]: 1.67, 95% confidence interval [CI], 1.07e2.62; within 30 minutes, OR: 1.61, 95% CI, 1.15e2.27), high-frequency cigarette dual users (5 minutes, OR: 2.85, 95% CI, 1.76e4.63; within 30 minutes, OR: 4.14, 95% CI, 2.96e5.80), and high-frequency dual users (5 minutes, OR: 4.46, 95% CI, 2.88e6.91; 30 minutes, OR: 3.94, 95% CI, 2.43e6.42). In addition, high-frequency e-cigarette dual users had significantly lower quit intention compared with both cigarette-only smokers and low-frequency dual users. Conclusions: Findings highlight the need for a standard, granulated classification of dual user, as important characteristics may vary between different categories. Future studies on dual use should consider categorizing dual use into the four classifications described in this study.

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand–drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule–drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body–drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.

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The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of b-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann-Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventysix participants were included (128 HIV+ and 48 HIV-); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm 3. Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV.

Local and metastatic relapses of prostate cancer often occur following attempted curative resection of the primary tumor, and up to 66% of local recurrences are associated with positive margins. Therefore, technologies that can improve the visualization of tumor margins and adjuvant therapies to ablate remaining tumor tissues are needed during surgical resection of prostate adenocarcinoma. Photodynamic agents have the potential to combine both fluorescence for image-guided surgery (IGS) and photodynamic therapy (PDT) to resect and ablate cancer cells. The objective of this study was to determine the utility of a targeted PDT agent for IGS and adjuvant PDT. Using a previously developed prostatespecific membrane antigen (PSMA)-targeted PDT agent, PSMA-1-Pc413, we showed that PSMA-1-Pc413 selectively highlighted PSMA-expressing tumors, allowing IGS and more complete tumor resection compared with white light surgery. Subsequent PDT further reduced tumor recurrence and extended animal survival significantly. This approach also enabled identification of tumor cells in lymph nodes. In summary, this study presents a potential new treatment option for patients with prostate cancer undergoing surgery, which improves tumor visualization and discrimination during surgery, including identification of cancer in lymph nodes.Significance: These findings present a photodynamic agent that can be used for both photodynamic therapy and image-guided surgery, allowing better visualization of tumor margins and elimination of residual tumor tissues.

Background Children with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood. Methods This is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2–10 years old in Uganda. PHIVs were on stable ART with HIV-1 RNA &lt;400 copies/mL. We measured markers of systemic inflammation, monocyte activation, and gut integrity. Kruskal-Wallis tests were used to compare markers by group and the Spearman correlation was used to assess correlations between biomarkers. Results The mean age of all participants was 7 years and 55% were girls. Among PHIVs, the mean CD4 % was 34%, 93% had a viral load ≤20 copies/mL, and 79% were on a nonnucleoside reverse transcriptase inhibitor regimen. Soluble cluster of differentiation 14 (sCD14), beta-D-glucan (BDG), and zonulin were higher in the PHIV group (P ≤ .01). Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide binding protein (LBP) did not differ between groups (P &gt; .05). Among PHIVs who were breastfed, levels of sCD163 and interleukin 6 (IL6) were higher than levels in PHIV who were not breastfed (P &lt; .05). Additionally, in PHIVs with a history of breastfeeding, sCD14, BDG, LBP, zonulin, and I-FABP correlated with several markers of systemic inflammation, including high-sensitivity C-reactive protein, IL6, d-dimer, and systemic tumor necrosis factor receptors I and II (P ≤ .05). Conclusions Despite viral suppression, PHIVs have evidence of altered gut permeability and fungal translocation. Intestinal damage and the resultant bacterial and fungal translocations in PHIVs may play a role in the persistent inflammation that leads to many end-organ diseases in adults. Despite viral suppression, children with perinatally acquired human immunodeficiency virus (HIV) in Uganda have evidence of alterations in intestinal permeability and fungal translocation, compared to HIV-exposed but uninfected and HIV-unexposed children, which may play a role in HIV-associated chronic inflammation.