Greater than 3-Log Reduction in Viable Coronavirus Aerosol Concentration in Ducted Ultraviolet-C (UV-C) Systems.

Control technologies to inactivate airborne viruses effectively are needed during the ongoing SARS-CoV-2 pandemic, and to guard against airborne transmitted diseases. We demonstrate that sealed UV-C flow reactors operating with fluences near 253 ± 1 nm of 13.9-49.6 mJ cm-2 efficiently inactivate coronaviruses in an aerosol. For measurements, porcine respiratory coronavirus (PRCV) was nebulized in a custom-built, 3.86 m wind tunnel housed in a biosafety level class II facility. The single pass log10 reduction of active coronavirus was in excess of 2.2 at a flow rate of 2439 L min-1 (13.9 mJ cm-2) and in excess of 3.7 (99.98% removal efficiency) at 684 L min-1 (49.6 mJ cm-2). Because virus titers resulting from sampling downstream of the UV-C reactor were below the limit of detection, the true log reduction is likely even higher than measured. Comparison of virus titration results to reverse transcriptase quantitative PCR and measurement of fluorescein concentrations (doped into the nebulized aerosol) reveals that the reduction in viable PRCV is primarily due to UV-C based inactivation, as opposed to physical collection of virus. The results confirm that UV-C flow reactors can efficiently inactivate coronaviruses through incorporation into HVAC ducts or recirculating air purifiers.

Wind tunnel-based testing of a photoelectrochemical oxidative filter-based air purification unit in coronavirus and influenza aerosol removal and inactivation.

Recirculating air purification technologies are employed as potential means of reducing exposure to aerosol particles and airborne viruses. Toward improved testing of recirculating air purification units, we developed and applied a medium-scale single-pass wind tunnel test to examine the size-dependent collection of particles and the collection and inactivation of viable bovine coronavirus (BCoV, a betacoronavirus), porcine respiratory coronavirus (PRCV, an alphacoronavirus), and influenza A virus (IAV), by a commercial air purification unit. The tested unit, the Molekule Air Mini, incorporates a MERV 16 filter as well as a photoelectrochemical oxidating layer. It was found to have a collection efficiency above 95.8% for all tested particle diameters and flow rates, with collection efficiencies above 99% for supermicrometer particles with the minimum collection efficiency for particles smaller than 100 nm. For all three tested viruses, the physical tracer-based log reduction was near 2.0 (99% removal). Conversely, the viable virus log reductions were found to be near 4.0 for IAV, 3.0 for BCoV, and 2.5 for PRCV, suggesting additional inactivation in a virus family- and genus-specific manner. In total, this work describes a suite of test methods which can be used to rigorously evaluate the efficacy of recirculating air purification technologies.

Chronic, Elevated Maternal Corticosterone During Pregnancy in the Mouse Increases Allergic Airway Inflammation in Offspring.

Allergic asthma is a chronic pulmonary disorder fundamentally linked to immune dysfunction. Since the immune system begins developing in utero, prenatal exposures can affect immune programming and increase risk for diseases such as allergic asthma. Chronic psychosocial stress during pregnancy is one such risk factor, having been associated with increased risk for atopic diseases including allergic asthma in children. To begin to define the underlying causes of the association between maternal stress and allergic airway inflammation in offspring, we developed a mouse model of chronic heightened stress hormone during pregnancy. Continuous oral administration of corticosterone (CORT) to pregnant mice throughout the second half of pregnancy resulted in an ~2-fold increase in circulating hormone in dams with no concomitant increase in fetal circulation, similar to the human condition. To determine how prolonged heightened stress hormone affected allergic immunity in offspring, we induced allergic asthma with house dust mite (HDM) and examined the airway immune response to allergen. Female mice responded to HDM more frequently and had a more robust immune cell response compared to their male counterparts, irrespective of maternal treatment. Male offspring from CORT-treated dams had a greater number of inflammatory cells in the lung in response to HDM compared to males from control dams, while maternal treatment did not affect immune cell numbers in females. Alternatively, maternal CORT caused enhanced goblet cell hyperplasia in female offspring following HDM, an effect that was not observed in male offspring. In summary, prenatal exposure to mild, prolonged heightened stress hormone had sexually dimorphic effects on allergic inflammation in airways of adult offspring.

Transgenerational Effects of Periconception Heavy Metal Administration on Adipose Weight and Glucose Homeostasis in Mice at Maturity.

We previously demonstrated that periconception maternal administration (2 mg/kg body weight each) of cadmium chloride (CdCl2) plus methylmercury (II) chloride (CH3HgCl) impaired glucose homeostasis and increased body weights and abdominal adipose tissue weight of male offspring in the F1 generation. However, transgenerational effects of this exposure have not been studied. Therefore, the effects of periconception Cd+Hg administration on indices of chronic diseases at adulthood in F2-F4 generations were examined. Male and female progeny of Cd+Hg periconceptionally treated females, and offspring of vehicle control females were bred with naïve CD1 mice to obtain F2 offspring, with additional crosses as above to the F4 generation (F1-F4 animals were not administered Cd+Hg). Birth weights and litter size were similar in all generations. Indices of impaired glucose homeostasis were observed in matrilineally descended F2 male offspring, including reduced glucose tolerance, along with increased basal phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307 suggesting altered insulin signaling. Reduced glucose tolerance was also seen in F4 males. Increased body weight and/or abdominal adiposity were observed through the F4 generation in males descended matrilineally from the treated female progenitors. Patrilineally derived F2 females displayed reduced glucose tolerance. Females (F2) patrilineally and matrilineally derived displayed significant kidney enlargement. Periconception administration of cadmium and mercury caused persistent transgenerational effects in offspring through the F4 generation in the absence of continued toxicant exposure, with persistent transgenerational effects inherited specifically through the matrilineal germline.

Correction: Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth.

[This corrects the article DOI: 10.1371/journal.pone.0188645.].

Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion in first-trimester trophoblast cells.

PROBLEM: Heightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes. METHODS OF STUDY: Studies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 µmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 µmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody. Invasion assays used Matrigel chambers. RESULTS: Cortisol inhibited expression of CSF2 (GM-CSF) and CSF3 (G-CSF) in trophoblast cells. Cortisol-associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs. CONCLUSION: In first-trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol-associated changes in trophoblast function could increase the risk for immune-mediated abortion or other adverse pregnancy outcomes.

Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth.

Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future.

Effects of Periconception Cadmium and Mercury Co-Administration to Mice on Indices of Chronic Diseases in Male Offspring at Maturity.

BACKGROUND: Long-term exposure to the heavy metals cadmium (Cd) and mercury (Hg) is known to increase the risk of chronic diseases. However, to our knowledge, exposure to Cd and Hg beginning at the periconception period has not been studied to date. OBJECTIVE: We examined the effect of Cd and Hg that were co-administered during early development on indices of chronic diseases in adult male mice. METHODS: Adult female CD1 mice were subcutaneously administered a combination of cadmium chloride (CdCl2) and methylmercury (II) chloride (CH3HgCl) (0, 0.125, 0.5, or 2.0 mg/kg body weight each) 4 days before and 4 days after conception (8 days total). Indices of anxiety-like behavior, glucose homeostasis, endocrine and molecular markers of insulin resistance, and organ weights were examined in adult male offspring. RESULTS: Increased anxiety-like behavior, impaired glucose homeostasis, and higher body weight and abdominal adipose tissue weight were observed in male offspring of treated females compared with controls. Significantly increased serum leptin and insulin concentrations and impaired insulin tolerance in the male offspring of dams treated with 2.0 mg/kg body weight of Cd and Hg suggested insulin resistance. Altered mRNA abundance for genes associated with glucose and lipid homeostasis (GLUT4, IRS1, FASN, ACACA, FATP2, CD36, and G6PC) in liver and abdominal adipose tissues as well as increased IRS1 phosphorylation in liver (Ser 307) provided further evidence of insulin resistance. CONCLUSIONS: Results suggest that the co-administration of Cd and Hg to female mice during the early development of their offspring (the periconception period) was associated with anxiety-like behavior, altered glucose metabolism, and insulin resistance in male offspring at adulthood.