Seasonal Variation of Dissolved Lead Speciation in Tagus Estuary, Portugal

The behavior of lead species from Tagus estuarine water collected during winter (January), spring (April), and summer (June) seasons were evaluated. Water samples were titrated with Pb+2 followed by differential pulse anodic stripping voltammetry (DPASV). Experimental voltammetric values were interpreted assuming a macromolecular heterogeneous ligand described in a simple way by two types of binding sites, CL1 and CL2, where CL1 is related to stronger binding groups with lower concentration compared to CL2. Water quality parameters like dissolved organic matter (DOC), pH, salinity, temperature, and total lead concentration were measured during the period under study. The results pointed to a higher concentration of CL1 and CL2 sites in April probably due to the phytoplankton bloom. The decrease of KL1 with the increase of salinity from winter to summer may be caused by the increase of major cations (as Ca2+) in solution. The trend of KL2 followed the pH shift in all seasons since an increase of pH favors Pb2+ complexation with CL2 sites. Finally, the decrease of DOC in summer could be responsible for the decrease in the concentration of the different sites in solution from April to June, with a similar decrease of 35±3% for all of them.

Impact of the COVID-19 Lockdown on Ophthalmological Assistance in the Emergency Department at a Spanish Primary Level Hospital

Purpose. To analyze the changes in ophthalmological emergencies during the COVID-19 pandemic lockdown at a Spanish primary level hospital. Methods. The number and type of emergencies attended in the emergency department of Hospital Universitario del Henares between March 10 and August 31, 2020 (COVID-19 cohort) were compared with the emergencies attended during the same period of 2019 (pre-COVID-19 cohort). Data on the diagnosis, patient age, and gender was retrospectively collected from the electronic medical records of the hospital. The different diagnoses were organized into “clusters,” which include those conditions that affect the same ocular tissue and that have similar clinical expression. Results. The number of ophthalmological emergencies during the study period was 841, compared to 1343 during the same month of 2019, which represents a reduction of 37.4%. The percentage reduction in each cluster was as follows: conjunctiva (−65.4%), cornea (−35.8%), uveitis (−3.6%), eyelid and orbital and lacrimal (−35.5%), strabismus (−60%), neuro-ophthalmology (−11.8%), retina (−10.6%), cataract (+16.4%), glaucoma (−37%), and miscellaneous (−45.1%). The number of people seen with viral conjunctivitis decreased by −87.1% compared to 2019. Patients with complications due to conjunctivitis also decreased: patients with pseudomembranes dropped from 16 to 4 cases and patients with corneal subepithelial infiltrates from 9 to 3 cases. Conclusions. Most diagnostic clusters showed a similar decrease. Clusters that included vision-threating conditions (retina, neuro-ophthalmology, and uveitis) remained mostly stable. During the COVID-19 lockdown, the diagnosis of adenoviral conjunctivitis decreased nearly 10 times. This fact may represent a decrease in the transmission of these infections.

Adipose MDM2 regulates systemic insulin sensitivity

The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.

163. MIC Shifts in Response to Increased Antibiotic Utilization During COVID-19 Pandemic

Background Multiple studies have shown that antibiotic utilization increased during the COVID-19 pandemic. However, the impact of this increased utilization has not been well established. The aim of this study is to describe the trends in minimum inhibitory concentrations for various antibiotics against common gram-negative pathogens observed since the start of the COVID-19 pandemic as compared to previous years. Methods This retrospective study was conducted at the Memphis VA. All respiratory, urine, and blood culture MicroScan results run from October 2017-March 2021 were analyzed. Only inpatient and emergency department data was included. The MIC50 and MIC90 of seven antibiotics for four of the most common pathogens were trended by quarterly intervals. Results MIC50 and MIC90 were compared using standardized breakpoints. As compared to previous years, Pseudomonas aeruginosa was noted to have the most sustained increase in MIC90 across various antibiotics. In the last 3 quarters of the study time frame, piperacillin-tazobactam mean MIC90 increased from 32 to 64, cefepime from 8 to > 16, and meropenem from 4 to > 8. Escherichia coli had a sustained increase in ceftriaxone MIC90 from < 1 to > 8 in the final quarter of 2020 and beginning of 2021. Klebsiella pneumonia was also found to have a sustained increase in cefepime mean MIC90 from < 1 to > 16 during the year of 2020, with return to previous MIC90 the following quarters. Conclusion Previous studies have clearly demonstrated a widespread increase in antibiotic utilization during the COVID era. Our study demonstrates how even short-term increases in antibiotic use can lead to shifts in MIC, if not outright resistance. This was demonstrated across multiple common gram-negative pathogens and to various broad-spectrum antibiotics which were commonly used more frequently during COVID-19. Further analysis will be needed to determine whether these trends continue or whether the decrease in antibiotic utilization in the recent months will lead to similar decrease in MIC. Disclosures All Authors: No reported disclosures

COVID-19 Restrictions Are Associated With a Significant Decrease of All Common Respiratory Viral Illnesses in Children

To combat the spread of coronavirus disease 2019 (COVID-19), significant measures were enacted including school and business closures, social distancing, and facial coverings. We hypothesized that this would have an impact on all respiratory infections in children. Using nasopharyngeal panel test results of children in the emergency department, we evaluated cross-sectional data from February to May in both 2019 and 2020. Respiratory panel testing included 11 common respiratory viruses and bacteria. After the restrictions were enacted, we observed a large drop in the number and percentage positive of all common respiratory viral infections in 2020 compared with the same time in 2019. When analyzing data from children <2 years old, a similar decrease was seen. Restrictions enacted to prevent the spread of COVID-19 were associated with a significant decrease in respiratory viral infections in children of all ages. This association could guide future public health recommendations and guidelines.

Temporary pause in the growth of atmospheric ethane and propane in 2015–2018

Atmospheric non-methane hydrocarbons (NMHCs) play an important role in the formation of secondary organic aerosols and ozone. After a multidecadal global decline in atmospheric mole fractions of ethane and propane – the most abundant atmospheric NMHCs – previous work has shown a reversal of this trend with increasing atmospheric abundances from 2009 to 2015 in the Northern Hemisphere. These concentration increases were attributed to the unprecedented growth in oil and natural gas (O&amp;NG) production in North America. Here, we supplement this trend analysis building on the long-term (2008–2010; 2012–2020) high-resolution (∼3 h) record of ambient air C2–C7 NMHCs from in situ measurements at the Greenland Environmental Observatory at Summit station (GEOSummit, 72.58 ∘ N, 38.48 ∘ W; 3210 m above sea level). We confirm previous findings that the ethane mole fraction significantly increased by +69.0 [+47.4, +73.2; 95 % confidence interval] ppt yr−1 from January 2010 to December 2014. Subsequent measurements, however, reveal a significant decrease by −58.4 [−64.1, −48.9] ppt yr−1 from January 2015 to December 2018. A similar reversal is found for propane. The upturn observed after 2019 suggests, however, that the pause in the growth of atmospheric ethane and propane might only have been temporary. Discrete samples collected at other northern hemispheric baseline sites under the umbrella of the NOAA cooperative global air sampling network show a similar decrease in 2015–2018 and suggest a hemispheric pattern. Here, we further discuss the potential contribution of biomass burning and O&amp;NG emissions (the main sources of ethane and propane) and conclude that O&amp;NG activities likely played a role in these recent changes. This study highlights the crucial need for better constrained emission inventories.

FC 032THE EFFECT OF AVACOPAN, A COMPLEMENT C5A RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS WITH RENAL DISEASE

Background and Aims Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life- or organ-threatening condition in which patients experience severe inflammation of small arteries. Renal involvement is common in ANCA-associated vasculitis and is correlated with high morbidity and mortality. Current treatment regimens have limited efficacy for renal disease in patients presenting with organ- or life-threatening ANCA-associated vasculitis. Avacopan, a novel orally-administered antagonist of the complement fragment C5a receptor (C5aR), was evaluated through a Phase 3 trial in patients with ANCA vasculitis. Efficacy and safety results have been previously reported; this abstract provides details of the effects on renal function in patients with renal involvement. Method The ADVOCATE trial was a randomized, double-blind, active controlled, double-dummy, 52-week treatment Phase 3 trial of 331 patients with ANCA-associated vasculitis. Patients were randomized 1:1 and received either a standard daily prednisone dosing with taper (i.e., starting at 60 mg / day tapered to 0 mg by Week 21), or daily avacopan. Background therapy included either: a) cyclophosphamide (oral or IV) followed by azathioprine, or, b) rituximab (four IV infusions). Patients with active glomerulonephritis at baseline were included in this analysis. Kidney function was analyzed based on the following parameters, which were assessed at pre-specified time-points: changes in the urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and Urinary Monocyte Chemoattractant Protein-1 (MCP-1):Creatinine ratio. Results At the baseline visit, 265 patients had renal disease. eGFR improved more in the avacopan group (n=131) compared to the prednisone group (n=134). At Week 26, eGFR increased 5.8 mL/min/1.73 m2 (from a baseline of 44.6 mL/min/1.73 m2), compared to 2.9 mL/min/1.73 m2 in the prednisone group (from a baseline of 45.6 mL/min/m2), P=0.046. At Week 52, the increases in eGFR were 7.3 mL/min/1.73 m2 and 4.1 mL/min/1.73 m2, respectively, P=0.029. The improvement was most prominent in subjects with Stage 4 kidney disease at baseline (eGFR &lt; 30 mL/min/1.73 m2), in whom eGFR improved 13.7 mL/min/1.73 m2 at Week 52 in the avacopan group (from a baseline of 21.1 mL/min/1.73 m2) compared to 8.2 mL/min/1.73 m2 in the prednisone group (from a baseline of 21.6 mL/min/1.73 m2), P=0.005. In addition to the differences in eGFR, a more rapid decrease in UACR was observed with avacopan; by Week 3 this difference was statistically significant, and at Week 4, a 40% decrease from baseline occurred in the avacopan group vs no change from baseline in the prednisone group (P&lt;0.0001). By Week 52, both groups showed a similar decrease in UACR from baseline. The urinary MCP-1:creatinine ratio decreased 59% in the avacopan group by Week 13 vs 52% in the prednisone group, P=0.03, but there was a similar decrease in the two treatment groups by Week 52. Conclusion Treatment with avacopan in patients with ANCA-associated vasculitis with renal disease led to greater recovery in eGFR when compared to standard prednisone therapy, especially in patients with Stage 4 kidney disease (eGFR &lt;30 mL/min/1.73 m2). Avacopan also led to more rapid improvement in the UACR and urinary MCP-1:creatinine ratio than prednisone. Since albuminuria is an independent risk factor for progression of renal disease (in addition to eGFR decline), the more rapid improvement in albuminuria with avacopan may also provide long-term benefit. These findings have important implications for the health of patients with ANCA-associated vasculitis.

mRNA vaccination compared to infection elicits an IgG-predominant response with greater SARS-CoV-2 specificity and similar decrease in variant spike recognition

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.

Chemical Modification of B4C Films and B4C/Pd Layers Stored in Different Environments

B4C/Pd multilayers with small d-spacing can easily degrade in the air, and the exact degradation process is not clear. In this work, we studied the chemical modification of B4C films and B4C/Pd double layers stored in four different environments: a dry nitrogen environment, the atmosphere, a dry oxygen-rich environment, and a wet nitrogen environment. The XANES spectra of the B4C/Pd layers placed in a dry oxygen-rich environment showed the most significant decrease in the σ* states of the B–C bonds and an increase in the π* states of the B–O bonds compared with the other samples. X-ray photoelectron spectroscopy (XPS) measurements of the samples placed in a dry oxygen-rich environment showed more intensive B-O binding signals in the B4C/Pd layers than in the single B4C film. The results of the Fourier-transform infrared spectroscopy (FTIR) showed a similar decrease in the B–C bonds and an increase in the B–O bonds in the B4C/Pd layers in contrast to the single B4C film placed in a dry oxygen-rich environment. We concluded that the combination of palladium catalysis and the high content of oxygen in the environment promoted the oxidization of boron, deteriorated the B4C composition.

Decreased Orexin Receptor 1 mRNA Expression in the Locus Coeruleus in Both Tau Transgenic rTg4510 and Tau Knockout Mice and Accompanying Ascending Arousal System Tau Invasion in rTg4510

Background: Sleep/wake disturbances (e.g., insomnia and sleep fragmentation) are common in neurodegenerative disorders, especially Alzheimer’s disease (AD) and frontotemporal dementia (FTD). These symptoms are somewhat reminiscent of narcolepsy with cataplexy, caused by the loss of orexin-producing neurons. A bidirectional relationship between sleep disturbance and disease pathology suggests a detrimental cycle that accelerates disease progression and cognitive decline. The accumulation of brain tau fibrils is a core pathology of AD and FTD-tau and clinical evidence supports that tau may impair the orexin system in AD/FTD. This hypothesis was investigated using tau mutant mice. Objective: To characterize orexin receptor mRNA expression in sleep/wake regulatory brain centers and quantify noradrenergic locus coeruleus (LC) and orexinergic lateral hypothalamus (LH) neurons, in tau transgenic rTg4510 and tau–/– mice. Methods: We used i n situ hybridization and immunohistochemistry (IHC) in rTg4510 and tau–/– mice. Results: rTg4510 and tau–/– mice exhibited a similar decrease in orexin receptor 1 (OX1R) mRNA expression in the LC compared with wildtype controls. IHC data indicated this was not due to decreased numbers of LC tyrosine hydroxylase-positive (TH) or orexin neurons and demonstrated that tau invades TH LC and orexinergic LH neurons in rTg4510 mice. In contrast, orexin receptor 2 (OX2R) mRNA levels were unaffected in either model. Conclusion: The LC is strongly implicated in the regulation of sleep/wakefulness and expresses high levels of OX1R. These findings raise interesting questions regarding the effects of altered tau on the orexin system, specifically LC OX1Rs, and emphasize a potential mechanism which may help explain sleep/wake disturbances in AD and FTD.