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• Pharmacological treatment for agitation can lead to adverse outcomes. • Non-pharmacological interventions are best practice for managing agitation symptoms. • Individualized music listening programs reduce agitation in patients with dementia. • This project highlights need for further study in patients with dementia in acute care. The sudden change in environment with hospitalization in patients with dementia can provoke feelings of agitation. Listening to music can be an effective intervention to decrease agitation because the part of the brain recognizing music is unaffected by dementia, and music can elicit feelings of happiness. This project aimed to reduce agitation in patients with Alzheimer's disease and related dementias (ADRD) by implementing an individualized music listening program. The sample included 21 patients diagnosed with ADRD admitted to a medical-surgical unit at a community hospital. The four-item Pittsburgh Agitation Scale (PAS) was completed by clinical staff to document the degree to which their patient exhibited four types of agitated behavior. A paired t-test yielded a statistically significant (p<0.001) decrease in total scores from pre-test (M =4.83, SD =2.10) to post-test (M =1.38, SD =1.40). The findings demonstrate that implementing an individualized music listening program reduces agitation in patients with ADRD. [ABSTRACT FROM AUTHOR]

Proximal tubular epithelial cells (PTEC) in the S1 segment of the kidney abundantly express sodium-glucose co-transporters (SGLT) that play a critical role in whole body glucose homeostasis. We recently reported suppression of RECK (Re version Inducing C ysteine Rich Protein with K azal Motifs), a membrane anchored endogenous MMP inhibitor and anti-fibrotic mediator, in the kidneys of db/db mice, a model of diabetic kidney disease (DKD), as well as in high glucose (HG) treated human kidney proximal tubule cells (HK−2). We further demonstrated that empagliflozin (EMPA), an SGLT2 inhibitor, reversed these effects. Little is known regarding the mechanisms underlying RECK suppression under hyperglycemic conditions, and its rescue by EMPA. Consistent with our previous studies, HG (25 mM) suppressed RECK expression in HK-2 cells. Further mechanistic investigations revealed that HG induced superoxide and hydrogen peroxide generation, oxidative stress-dependent TRAF3IP2 upregulation, NF-κB and p38 MAPK activation, inflammatory cytokine expression (IL-1β, IL-6, TNF-α, and MCP-1), miR-21 induction, MMP2 activation, and RECK suppression. Moreover, RECK gain-of-function inhibited HG-induced MMP2 activation and HK-2 cell migration. Similar to HG, advanced glycation end products (AGE) induced TRAF3IP2 and suppressed RECK, effects that were inhibited by EMPA. Importantly, EMPA treatment ameliorated all of these deleterious effects, and inhibited epithelial-to-mesenchymal transition (EMT) and HK-2 cell migration. Collectively, these findings indicate that hyperglycemia and associated AGE suppress RECK expression via oxidative stress/TRAF3IP2/NF-κB and p38 MAPK/miR-21 induction. Furthermore, these results suggest that interventions aimed at restoring RECK or inhibiting SGLT2 have the potential to treat kidney inflammatory response/fibrosis and nephropathy under chronic hyperglycemic conditions, such as DKD. Unlabelled Image • High glucose and associated AGE suppress RECK, an anti-fibrotic MMP-regulator, in proximal tubule epithelial cells (PTEC). • High glucose induces oxidative stress and TRAF3IP2-dependent inflammatory cytokine expression in renal PTEC. • Empagliflozin, a SGLT2 inhibitor, reverses HG- and AGE-induced RECK suppression and TRAF3IP2 upregulation in renal PTEC. • Empagliflozin suppresses EMT and PTEC migration, hallmarks of diabetic kidney disease. • Empagliflozin has therapeutic potential in diabetic kidney disease. [ABSTRACT FROM AUTHOR]

• Paraxanthine (PARA) is a more reliable population biomarker than pMMoV for WBE. • Normalization coefficients can be used for direct SARS-CoV-2 normalization. • Clinical case numbers should be normalized by real-time population. • Paraxanthine demonstrated excellent utility for estimating real-time population. • Normalization by PARA improved the correlation between viral load and case number. Wastewater-based epidemiology (WBE) has been one of the most cost-effective approaches to track the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in the communities since the coronavirus disease 2019 (COVID-19) outbreak in 2020. Normalizing SARS-CoV-2 concentrations by the population biomarkers in wastewater is critical for interpreting the viral loads, comparing the epidemiological trends among the sewersheds, and identifying the vulnerable communities. In this study, five population biomarkers, pepper mild mottle virus (PMMoV), creatinine (CRE), 5-hydroxyindoleacetic acid (5-HIAA), caffeine (CAF) and its metabolite paraxanthine (PARA) were investigated and validated for their utility in normalizing the SARS-CoV-2 loads through two normalizing approaches using the data from 64 wastewater treatment plants (WWTPs) in Missouri. Their utility in assessing the real-time population contributing to the wastewater was also evaluated. The best performing candidate was further tested for its capacity for improving correlation between normalized SARS-CoV-2 loads and the clinical cases reported in the City of Columbia, Missouri, a university town with a constantly fluctuating population. Our results showed that, except CRE, the direct and indirect normalization approaches using biomarkers allow accounting for the changes in wastewater dilution and differences in relative human waste input over time regardless flow volume and population of the given WWTP. Among selected biomarkers, PARA is the most reliable population biomarker in determining the SARS-CoV-2 load per capita due to its high accuracy, low variability, and high temporal consistency to reflect the change in population dynamics and dilution in wastewater. It also demonstrated its excellent utility for real-time assessment of the population contributing to the wastewater. In addition, the viral loads normalized by the PARA-estimated population significantly improved the correlation (rho =0.5878, p < 0.05) between SARS-CoV-2 load per capita and case numbers per capita. This chemical biomarker complements the current normalization scheme recommended by CDC and helps us understand the size, distribution, and dynamics of local populations for forecasting the prevalence of SARS-CoV2 within each sewershed. [Display omitted] [ABSTRACT FROM AUTHOR]

• Wastewater facilities that exhibit SARS-CoV-2 suppression have been identified. • Average SARS-CoV-2 load per reported case was calculated to be 5 × 1011. • Metabolomic profiling was used to identify the compounds suppressing the SARS-CoV-2. • Four compounds are positively correlated with SARS-CoV-2 signal suppression rates. Recent SARS-CoV-2 wastewater-based epidemiology (WBE) surveillance have documented a positive correlation between the number of COVID-19 patients in a sewershed and the level of viral genetic material in the wastewater. Efforts have been made to use the wastewater SARS-CoV-2 viral load to predict the infected population within each sewershed using a multivariable regression approach. However, reported clear and sustained variability in SARS-CoV-2 viral load among treatment facilities receiving industrial wastewater have made clinical prediction challenging. Several classes of molecules released by regional industries and manufacturing facilities, particularly the food processing industry, can significantly suppress the SARS-CoV-2 signals in wastewater by breaking down the lipid-bilayer of the membranes. Therefore, a systematic ranking process in conjugation with metabolomic analysis was developed to identify the wastewater treatment facilities exhibiting SARS-CoV-2 suppression and identify and quantify the chemicals suppressing the SARS-COV-2 signals. By ranking the viral load per diagnosed case among the sewersheds, we successfully identified the wastewater treatment facilities in Missouri, USA that exhibit SARS-CoV-2 suppression (significantly lower than 5 × 1011 gene copies/reported case) and determined their suppression rates. Through both untargeted global chemical profiling and targeted analysis of wastewater samples, 40 compounds were identified as candidates of SARS-CoV-2 signal suppressors. Among these compounds, 14 had higher concentrations in wastewater treatment facilities that exhibited SARS-CoV-2 signal suppression compared to the unsuppressed control facilities. Stepwise regression analyses indicated that 4-nonylphenol, palmitelaidic acid, sodium oleate, and polyethylene glycol dioleate are positively correlated with SARS-CoV-2 signal suppression rates. Suppression activities were further confirmed by incubation studies, and the suppression kinetics for each bioactive compound were determined. According to the results of these experiments, bioactive molecules in wastewater can significantly reduce the stability of SARS-CoV-2 genetic marker signals. Based on the concentrations of these chemical suppressors, a correction factor could be developed to achieve more reliable and unbiased surveillance results for wastewater treatment facilities that receive wastewater from similar industries. [Display omitted] [ABSTRACT FROM AUTHOR]