Lactational transfer of sulforaphane-N-acetylcysteine in vivo and in human breast milk.

Sulforaphane (SFN) is a bioactive phytonutrient found in cruciferous vegetables. There is a lack of detailed information on the lactational transfer of SFN and SFN metabolites, and potential pharmacological effects on breastfeeding infants. We carried out two maternal supplementation studies in a mouse model, wherein lactating dams received either vehicle, 300 or 600 ppm SFN from postnatal day (PND) 1 to 5, or in a second experiment, vehicle or 600 ppm SFN from PND 1 to 14. The parent compound was only detectable in milk and plasma from dams receiving 600 ppm SFN for five days. The predominant metabolite SFN-N-acetylcysteine (SFN-NAC) was readily detected in milk from dams receiving 300 and 600 ppm SFN for five days or 600 ppm for 14 days. Maternal SFN-NAC plasma levels were elevated in both 600 ppm groups. Maternal hepatic and pulmonary expression of NRF2-related genes, Nqo1, Gsta2, Gstm1, and Gstp1, were significantly increased, generally following a dose-response; however, offspring induction varied. PND5 neonates in the 600-ppm group exhibited significantly elevated expression of Nqo1, Gsta2, and Gstp1 in liver, and Gstm1 and Gstp1 in lung. Findings support maternal dietary supplementation with SFN induces NRF2-related gene expression in neonates via lactational transfer of SFN-NAC. However, NQO1 enzyme activity was not significantly elevated, highlighting the need to optimize dosing strategy. Additionally, in a pilot investigation of lactating women consuming a typical diet, without any purified SFN supplementation, 7 out of 8 breast milk samples showed SFN-NAC above the limit of quantification (LOQ). Notably, the one sample below the LOQ was collected from the only participant who reported no consumption of cruciferous vegetables in the past 24 h. The parent compound was not detected in any of the human breast milk samples. Overall, these data indicate lactational transfer of SFN-NAC at dietary relevant levels. Future studies are needed to evaluate pharmacokinetics and pharmacodynamics of lactational transfer for potential preventive or therapeutic effects in breastfeeding children.

Air Pollutant Patterns and Human Health Risk following the East Palestine, Ohio, Train Derailment.

On February 3, 2023, a train carrying numerous hazardous chemicals derailed in East Palestine, OH, spurring temporary evacuation of residents and a controlled burn of some of the hazardous cargo. Residents reported health symptoms, including headaches and respiratory, skin, and eye irritation. Initial data from U.S. Environmental Protection Agency (EPA) stationary air monitors indicated levels of potential concern for air toxics based on hazard quotient calculations. To provide complementary data, we conducted mobile air quality sampling on February 20 and 21 using proton transfer reaction-mass spectrometry. Measurements were taken at 1 s intervals along routes designed to sample both close to and farther from the derailment. Mobile air monitoring indicated that average concentrations of benzene, toluene, xylenes, and vinyl chloride were below minimal risk levels for intermediate and chronic exposures, similar to EPA stationary monitoring data. Levels of acrolein were high relative to those of other volatile organic compounds, with spatial analyses showing levels in East Palestine up to 6 times higher than the local rural background. Nontargeted analyses identified levels of additional unique compounds above background levels, some displaying spatiotemporal patterns similar to that of acrolein and others exhibiting distinct hot spots. These initial findings warrant follow-up mobile air quality monitoring to characterize longitudinal exposure and risk levels.

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy.

BACKGROUND: Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, [Formula: see text] 100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity. RESULTS: Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5-13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1ß (IL-1 [Formula: see text]) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer. CONCLUSIONS: Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.

Quantifying changes in respiratory syncytial virus-associated hospitalizations among children in Texas during COVID-19 pandemic using records from 2006 to 2021.

Aim: To quantify changes on RSV- associated hospitalizations during COVID-19 pandemic, among children four years of age or younger at the state and county levels of Texas using routinely acquired hospital admission records. Methods: We used the Texas Public Use Data Files (PUDF) of the Department of State Human Services (DSHS) to obtain hospital admissions and healthcare outcomes from 2006 to 2021. We used the 2006-2019 period to estimate a long-term temporal trend and predict expected values for 2020-2021. Actual and predicted values were used to quantify changes in seasonal trends of the number of hospital admissions and mean length of hospital stay. Additionally, we calculated hospitalization rates and assessed their similarity to rates reported in the RSV Hospitalization Surveillance Network (RSV-NET). Results: An unusually low number of hospitalizations in 2020 was followed by an unusual peak in the third quarter of 2021. Hospital admissions in 2021 were approximately twice those in a typical year. The mean length of hospital stay typically followed a seasonal trend before COVID-19, but increased by a factor of ∼6.5 during the pandemic. Spatial distribution of hospitalization rates revealed localized healthcare infrastructure overburdens during COVID-19. RSV associated hospitalization rates were, on average, two times higher than those of RSV-NET. Conclusion: Hospital admission data can be used to estimate long-term temporal and spatial trends and quantify changes during events that exacerbate healthcare systems, such as pandemics. Using the mean difference between hospital rates calculated with hospital admissions and hospital rates obtained from RSV-NET, we speculate that state-level hospitalization rates for 2022 could be at least twice those observed in the two previous years, and the highest in the last 17 years.

Gestational exposure to particulate air pollution exacerbates the growth phenotypes induced by preconception paternal alcohol use: a multiplex model of exposure.

It is now clear that parental histories of drug use, toxicant exposure, and social stress all have a significant influence on the health and development of the next generation. However, the ability of epigenetic parental life memories to interact with subsequent gestational exposures and cumulatively modify the developmental trajectory of the offspring remains an unexplored perspective in toxicology. Studies from our laboratory have identified male-specific postnatal growth restriction in a mouse model of chronic, preconception paternal alcohol exposure. The goal of the current study was to determine if paternal alcohol use, before conception, could modify the susceptibility of the offspring to a completely separate exposure encountered by the mother during pregnancy. In independent experiments, we previously identified altered developmental programming and increased markers of severe asthma induced by gestational exposure to particulate air pollution. In this study, male mice were exposed to either the control or alcohol preconception treatments, then mated to naive females, which we subsequently exposed to an ultrafine mixture of particulate matter via inhalation. Individually, neither preconception paternal drinking nor gestational exposures to particulate air pollution impacted the postnatal growth of female offspring. However, when both exposures were combined, females displayed a 30% reduction in weight gain. Unexpectedly, this exposure paradigm resulted in a dramatic postnatal increase in litter loss due to maternal cannibalism, which prevented additional measures of offspring health. These preliminary studies provide evidence of a complex interplay between preconception life history and intrauterine environmental factors in the control of postnatal growth.

Rapid Tuberculosis Diagnosis Using Reporter Enzyme Fluorescence.

Tuberculosis is the most frequent cause of death in humans from a single infectious agent. Due to low numbers of bacteria present in sputum during early infection, diagnosis does not usually occur until >3 to 4 months after symptoms develop. We created a new more sensitive diagnostic that can be carried out in 10 min with no processing or technical expertise. This assay utilizes the Mycobacterium tuberculosis-specific biomarker BlaC in reporter enzyme fluorescence (REF) that has been optimized for clinical samples, designated REFtb, along with a more specific fluorogenic substrate, CDG-3. We report the first evaluation of clinical specimens with REFtb assays in comparison to the gold standards for tuberculosis diagnosis, culture and smear microscopy. REFtb assays allowed diagnosis of 160 patients from 16 different countries with a sensitivity of 89% for smear-positive, culture-positive samples and 88% for smear-negative, culture-positive samples with a specificity of 82%. The negative predictive value of REFtb for tuberculosis infection is 93%, and the positive predictive value is 79%. Overall, these data point toward the need for larger accuracy studies by third parties using a commercially available REFtb kit to determine whether incorporation of REFtb into the clinical toolbox for suspected tuberculosis patients would improve case identification. If results similar to our own can be obtained by all diagnostic laboratories, REFtb would allow proper treatment of more than 85% of patients that would be missed during their initial visit to a clinic using current diagnostic strategies, reducing the potential for further spread of disease.