Stratified Simple Random Sampling Versus Volunteer Community-Wide Sampling for Estimates of COVID-19 Prevalence.

Objectives. To evaluate community-wide prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using stratified simple random sampling. Methods. We obtained data for the prevalence of SARS-CoV-2 in Jefferson County, Kentucky, from adult random (n = 7296) and volunteer (n = 7919) sampling over 8 waves from June 2020 through August 2021. We compared results with administratively reported rates of COVID-19. Results. Randomized and volunteer samples produced equivalent prevalence estimates (P < .001), which exceeded the administratively reported rates of prevalence. Differences between them decreased as time passed, likely because of seroprevalence temporal detection limitations. Conclusions. Structured targeted sampling for seropositivity against SARS-CoV-2, randomized or voluntary, provided better estimates of prevalence than administrative estimates based on incident disease. A low response rate to stratified simple random sampling may produce quantified disease prevalence estimates similar to a volunteer sample. Public Health Implications. Randomized targeted and invited sampling approaches provided better estimates of disease prevalence than administratively reported data. Cost and time permitting, targeted sampling is a superior modality for estimating community-wide prevalence of infectious disease, especially among Black individuals and those living in disadvantaged neighborhoods. (Am J Public Health. 2023;113(7):768-777. https://doi.org/10.2105/AJPH.2023.307303).

New roles of the Na+/H+ exchange regulatory factor 1 scaffolding protein: a review.

Na+/H+ exchange regulatory factor 1 (NHERF1), a member of a PDZ scaffolding protein family, was first identified as an organizer of membrane-bound protein complexes composed of hormone receptors, signal transduction pathways, and electrolyte and mineral transporters and channels. NHERF1 is involved in the regulation of Na+/H+ exchanger 3, Na+-dependent phosphate transporter 2a, and Na+-K+-ATPase through its ability to scaffold these transporters to the plasma membrane, allowing regulation of these protein complexes with their associated hormone receptors. Recently, NHERF1 has received increased interest in its involvement in a variety of functions, including cell structure and trafficking, tumorigenesis and tumor behavior, inflammatory responses, and tissue injury. In this review, we highlight the evidence for the expansive role of NHERF1 in cell biology and speculate on the implications for renal physiology and pathophysiology.

Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity after SARS-CoV-2 Vaccination.

BACKGROUND: The impact of chronic health conditions (CHCs) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. METHODS: We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated adult residents of Jefferson County, Kentucky, USA, from April 2021 to August 2021. Serostatus was determined by qualitative analysis of SARS-CoV-2-specific Spike IgG antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. RESULTS: Of the 5178 fully vaccinated participants, 51 were seronegative and 5127 were seropositive. Chronic kidney disease (CKD) and autoimmune disease showed the highest association with negative serostatus in fully vaccinated individuals. The absence of any CHC was strongly associated with positive serostatus. The risk of negative serostatus increased as the total number of pre-existing CHCs increased. Similarly, the use of two or more CHC-related medications was associated with seronegative status. CONCLUSIONS: The presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. The absence of any CHC was protective and increased the likelihood of a positive serological response. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

Public Awareness of and Support for the Use of Wastewater for SARS-CoV-2 Monitoring: A Community Survey in Louisville, Kentucky.

The majority of sewer systems in the United States and other countries are operated by public utilities. In the absence of any regulation, the public perception of wastewater monitoring for population health biomarkers is an important consideration for a public utility commission when allocating resources for this purpose. We conducted a survey in August 2021 as part of an ongoing COVID-19 community prevalence study in Louisville/Jefferson County, KY, US. The survey comprised seven questions about wastewater awareness and privacy concerns and was sent to approximately 35 000 households randomly distributed within the county. A total of 1220 adults were involved in the probability sample, and data from 981 respondents were used in the analysis. A total of 2444 adults additionally responded to the convenience sample, and data from 1751 respondents were used in the analysis. The samples were weighted to obtain estimates representative of all adults in the county. Public awareness of tracking the virus that causes COVID-19 in sewers was low. Opinions strongly support the public disclosure of monitoring results. Responses showed that people more strongly supported measurements in the largest areas (>50 000 households), typically representing population levels found in a large community wastewater treatment plant. Those with a history of COVID-19 infection were more likely to support highly localized monitoring. Understanding wastewater surveillance strategies and privacy concern thresholds requires an in-depth and comprehensive analysis of public opinion for continued success and effective public health monitoring.

Quantifying the relationship between sub-population wastewater samples and community-wide SARS-CoV-2 seroprevalence.

Robust epidemiological models relating wastewater to community disease prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community disease prevalence due to inherent biases. This study conducted serial stratified randomized samplings to estimate the prevalence of SARS-CoV-2 antibodies in 3717 participants, and obtained weekly samples of community wastewater for SARS-CoV-2 concentrations in Jefferson County, KY (USA) from August 2020 to February 2021. Using an expanded Susceptible-Infected-Recovered model, the longitudinal estimates of the disease prevalence were obtained and compared with the wastewater concentrations using regression analysis. The model analysis revealed significant temporal differences in epidemic peaks. The results showed that in some areas, the average incidence rate, based on serological sampling, was 50 % higher than the health department rate, which was based on convenience sampling. The model-estimated average prevalence rates correlated well with the wastewater (correlation = 0.63, CI (0.31,0.83)). In the regression analysis, a one copy per ml-unit increase in weekly average wastewater concentration of SARS-CoV-2 corresponded to an average increase of 1-1.3 cases of SARS-CoV-2 infection per 100,000 residents. The analysis indicates that wastewater may provide robust estimates of community spread of infection, in line with the modeled prevalence estimates obtained from stratified randomized sampling, and is therefore superior to publicly available health data.

Na/H Exchange Regulatory Factor 1 Deficient Mice Show Evidence of Oxidative Stress and Altered Cisplatin Pharmacokinetics.

(1) Background: One third of patients who receive cisplatin develop an acute kidney injury. We previously demonstrated the Na/H Exchange Regulatory Factor 1 (NHERF1) loss resulted in increased kidney enzyme activity of the pentose phosphate pathway and was associated with more severe cisplatin nephrotoxicity. We hypothesized that changes in proximal tubule biochemical pathways associated with NHERF1 loss alters renal metabolism of cisplatin or response to cisplatin, resulting in exacerbated nephrotoxicity. (2) Methods: 2-4 month-old male wild-type and NHERF1 knock out littermate mice were treated with either vehicle or cisplatin (20 mg/kg dose IP), with samples taken at either 4, 24, or 72 h. Kidney injury was determined by urinary neutrophil gelatinase-associated lipocalin and histology. Glutathione metabolites were measured by HPLC and genes involved in glutathione synthesis were measured by qPCR. Kidney handling of cisplatin was assessed by a kidney cortex measurement of γ-glutamyl transferase activity, Western blot for γ-glutamyl transferase and cysteine S-conjugate beta lyase, and ICP-MS for platinum content. (3) Results: At 24 h knock out kidneys show evidence of greater tubular injury after cisplatin and exhibit a decreased reduced/oxidized glutathione ratio under baseline conditions in comparison to wild-type. KO kidneys fail to show an increase in γ-glutamyl transferase activity and experience a more rapid decline in tissue platinum when compared to wild-type. (4) Conclusions: Knock out kidneys show evidence of greater oxidative stress than wild-type accompanied by a greater degree of early injury in response to cisplatin. NHERF1 loss has no effect on the initial accumulation of cisplatin in the kidney cortex but is associated with an altered redox status which may alter the activity of enzymes involved in cisplatin metabolism.

Serological assessment of SARS-CoV-2 infection during the first wave of the pandemic in Louisville Kentucky.

Serological assays intended for diagnosis, sero-epidemiologic assessment, and measurement of protective antibody titers upon infection or vaccination are essential for managing the SARS-CoV-2 pandemic. Serological assays measuring the antibody responses against SARS-CoV-2 antigens are readily available. However, some lack appropriate characteristics to accurately measure SARS-CoV-2 antibodies titers and neutralization. We developed an Enzyme-linked Immunosorbent Assay (ELISA) methods for measuring IgG, IgA, and IgM responses to SARS-CoV-2, Spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins. Performance characteristics of sensitivity and specificity have been defined. ELISA results show positive correlation with microneutralization and Plaque Reduction Neutralization assays with infectious SARS-CoV-2. Our ELISA was used to screen healthcare workers in Louisville, KY during the first wave of the local pandemic in the months of May and July 2020. We found a seropositive rate of approximately 1.4% and 2.3%, respectively. Our analyses demonstrate a broad immune response among individuals and suggest some non-RBD specific S IgG and IgA antibodies neutralize SARS-CoV-2.

Effects of body protection vests and experience levels in prevention of equestrian injuries.

OBJECTIVES: To investigate the risk reduction and benefit of wearing body protection/safety vests in equestrian sports. METHODS: A comparison of equestrians wearing body protective vests and those not wearing vests was performed using incident report data of 718 participants in the United States Pony Clubs during 2011-2017. Data obtained included age, gender, certification level of member, type of activity, description of incident, description of injuries, what protective equipment was worn and other possible contributing factors. RESULTS: While wearing body protective vests when riding on the flat or for show jumping was not correlated with a decrease in injuries, wearing vests for cross country was correlated with decrease in reported injuries (p=0.036) and showed a trend towards a lower incident severity level (p=0.062). Wearing body protection during cross country reduced the relative risk of injury by 56%. While the volume of incidents varied with a rider's experience level, the number of serious injuries did not appear to correlate with lesser equestrian experience. CONCLUSIONS: While equestrian sports are considered to have a certain degree of risk associated with them, there are ways to make them safer. Wearing safety equipment, such as helmets and body protection, and obtaining education and experience can lessen the chance of incurring serious injuries.