We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)mac239tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIVmac251.Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads (VL) upon infection. Circulating CD4+and CD8+T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+T cells may play a role in protection.

Background: Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women. Hypothesis: Many female patients with "normal" traditional risk factors or low atherosclerotic cardiovascular disease (ASCVD) risk scores may harbor high risk related to elevated levels of Lp(a). Methods: A retrospective, cross-sectional study of consecutive female patients presenting to Heart Centers for Women was performed. Discordance between low-density lipoprotein cholesterol (LDL-C) and Lp(a) was determined. The ASCVD risk and Reynolds Risk Score models A (RRS-A) and B (RRS-B) were calculated, and level of agreement in patients meeting treatment threshold (≥7.5% for ASCVD, ≥10% for RRS-A and RRS-B) were compared. Results: Among 713 women, 290 (41%) had elevated Lp(a); however, LDL-C and Lp(a) were weakly correlated (r = 0.08). Significant discordance was observed between abnormal LDL-C and Lp(a) levels (McNemar P = 0.03). There was moderate correlation between RRS-A and ASCVD risk (r = 0.71, P < 0.001), and Bland-Altman plot showed diminished correlation with increased risk. More patients met treatment threshold by ASCVD risk estimation, but nearly 1 out of 20 patients met treatment threshold by RRS-A but not ASCVD score. Conclusions: There is high prevalence of elevated Lp(a) among women presenting to Heart Centers for Women. Although traditional risk markers such as elevated LDL-C or high ASCVD risk may be absent in some women, elevated Lp(a) may identify patients who may benefit from aggressive risk-factor modification and pharmacologic therapy.

With the advancement in lineage-specific differentiation from human pluripotent stem cells (hPSCs), downstream cell separation has now become a critical step to produce hPSC-derived products. Since differentiation procedures usually result in a heterogeneous cell population, cell separation needs to be performed either to enrich the desired cell population or remove the undesired cell population. This article summarizes recent advances in separation processes for hPSC-derived cells, including the standard separation technologies, such as magnetic-activated cell sorting, as well as the novel separation strategies, such as those based on adhesion strength and metabolic flux. Specifically, the downstream bioprocessing flow and the identification of surface markers for various cell lineages are discussed. While challenges remain for large-scale downstream bioprocessing of hPSC-derived cells, the rational quality-by-design approach should be implemented to enhance the understanding of the relationship between process and the product and to ensure the safety of the produced cells.

Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [β (95% confidence interval (CI)) = −0.65 (−1.21, −0.09)] and Animal Naming scores [β (95% CI) = −1.54 (−3.00, −0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [β (95% CI) = −0.35 (−0.70, −0.006)] and the difference in AVLT scores [β (95% CI) = −0.40 (−0.77, −0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of the biomarkers were significantly associated with olfactory function.

Objectives: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs). Methods: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al. Results: Median (interquartile range (IQR)) Al measurements were: 15 μg/g dry bone (IQR = 28) for bone Al; 34.9 μg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (β = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (β = 0.98, 95% CI: -0.14, 2.1; β = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant. Conclusions: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.