Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots.

Background: In the earliest days of COVID-19 pandemic, the collection of dried blood spots (DBS) enabled public health laboratories to undertake population-scale seroprevalence studies to estimate rates of SARS-CoV-2 exposure. With SARS-CoV-2 seropositivity levels now estimated to exceed 94% in the United States, attention has turned to using DBS to assess functional (neutralizing) antibodies within cohorts of interest. Methods: Contrived DBS eluates from convalescent, fully vaccinated and pre-COVID-19 serum samples were evaluated in SARS-CoV-2 plaque reduction neutralization titer (PRNT) assays, a SARS-CoV-2 specific 8-plex microsphere immunoassay, a cell-based pseudovirus assay, and two different spike-ACE2 inhibition assays, an in-house Luminex-based RBD-ACE2 inhibition assay and a commercial real-time PCR-based inhibition assay (NAB-Sure™). Results: DBS eluates from convalescent individuals were compatible with the spike-ACE2 inhibition assays, but not cell-based pseudovirus assays or PRNT. However, the insensitivity of cell-based pseudovirus assays was overcome with DBS eluates from vaccinated individuals with high SARS-CoV-2 antibody titers. Conclusion: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.

Characterization of African-American Super-Agers in the National Alzheimer's Coordinating Center cohort.

BACKGROUND: "Super-agers" are adults aged ≥80 with cognitive performance similar to persons two to three decades younger. Characteristics such as larger hippocampal volume, APOE-ε4 allele absence, higher educational attainment, female sex, and lifelong cognitive stimulation are associated with cognitive performance compatible with super-aging. These findings are based on predominantly white research samples. Limited data are available on African-American super-agers. To fill this gap, we explored potential factors associated with super-aging in older African-American adults. METHODS: Data from African-American participants aged ≥80 in the National Alzheimer's Coordinating Center (NACC) dataset were analyzed. Using global Clinical Dementia Rating (CDR) scores, participants were first categorized as impaired (score ≥0.5) or non-impaired/normal cognition (NC) (score = 0). From the NC group, super-agers were identified using NACC-data-driven cutoffs. Participants were considered super-agers if their memory performance was similar to persons aged 50-60 with NC, and their performance on other domains was within one standard deviation of the mean for persons aged ≥80. We examined group characteristics (NC, super-ager, impaired) using chi-square and ANOVA with pairwise comparisons. Multinomial logistic regression, adjusted for sex and education, evaluated correlates of super-ager group assignment. RESULTS: Data for 1285 African-American participants aged ≥80 were analyzed. We identified 24.7% (n = 316) NC, 4.8% (n = 61) super-agers, and 70.6% (n = 905) impaired. Super-agers were mostly female and more educated, had similar vascular comorbidities as the other groups, and had less sleep disorders, depression, and alcohol use. After adjusting for sex and education, super-ager group assignment was associated with less sleep disorders, less depression, and moderate alcohol use. CONCLUSIONS: Participants with controlled vascular risk, mental health, alcohol use, and sleep disorders tended to be in the super-ager group. These factors may be important focus areas in clinical practice to support cognitive resilience with aging in older African-American adults.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.

Use of Self-Collected Dried Blood Spots and a Multiplex Microsphere Immunoassay to Measure IgG Antibody Response to COVID-19 Vaccines.

Serosurveys can determine the extent and spread of a pathogen in populations. However, collection of venous blood requires trained medical staff. Dried blood spots (DBS) are a suitable alternative because they can be self-collected and stored/shipped at room temperature. As COVID-19 vaccine deployment began in early 2021, we rapidly enrolled laboratory employees in a study to evaluate IgG antibody levels following vaccination. Participants received a DBS collection kit, self-collection instructions, and a brief questionnaire. Three DBS were collected by each of 168 participants pre- and/or postvaccination and tested with a multiplex microsphere immunoassay (MIA) that separately measures IgG antibodies to SARS-CoV-2 spike-S1 and nucleocapsid antigens. Most DBS (99.6%, 507/509) were suitable for testing. Participants with prior SARS-CoV-2 infection (n = 7) generated high S antibody levels after the first vaccine dose. Naïve individuals (n = 161) attained high S antibody levels after the second dose. Similar antibody levels were seen among those vaccinated with Moderna (n = 29) and Pfizer-BioNTech (n = 137). For those receiving either mRNA vaccine, local side effects were more common after the first vaccine dose, whereas systemic side effects were more common after the second dose. Individuals with the highest antibody levels in the week prior to the second vaccine dose experienced more side effects from the second dose. Our study demonstrated that combining self-collected DBS and a multiplex MIA is a convenient and effective way to assess antibody levels to vaccination and could easily be used for population serosurveys of SARS-CoV-2 or other emerging pathogens. IMPORTANCE Serosurveys are an essential tool for assessing immunity in a population (1, 2). However, common barriers to effective serosurveys, particularly during a pandemic, include high-costs, resources required to collect venous blood samples, lack of trained laboratory technicians, and time required to perform the assay. By utilizing self-collected dried blood spots (DBS) and our previously developed high-throughput microsphere immunoassay, we were able to significantly reduce many of these common challenges. Participants were asked to self-collect three DBS before and/or after they received their COVID-19 vaccines to measure antibody levels following vaccination. Participants successfully collected 507 DBS that were tested for IgG antibodies to the spike and nucleocapsid proteins of SARS-CoV-2. When used with self-collected DBS, our relatively low-cost assay significantly reduced common barriers to collecting serological data from a population and was able to effectively assess antibody response to vaccination.

Intracerebroventricular dosing of N-sulfoglucosamine sulfohydrolase in mucopolysaccharidosis IIIA mice reduces markers of brain lysosomal dysfunction.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease. Enzyme replacement therapy has been proposed, but further evaluation of the treatment strategy is needed. Here, we used Chinese hamster ovary cells to produce a highly soluble and fully active recombinant human sulfamidase (rhSGSH). We discovered that rhSGSH utilizes both the CI-MPR and LRP1 receptors for uptake into patient fibroblasts. A single intracerebroventricular (ICV) injection of rhSGSH in MPS IIIA mice resulted in a tissue half-life of 9 days and widespread distribution throughout the brain. Following a single ICV dose, both total HS and the MPS IIIA disease-specific HS-NRE were dramatically reduced, reaching a nadir 2 weeks post dose. The durability of effect for reduction of both substrate and protein markers of lysosomal dysfunction and a neuroimmune response lasted through the 56 days tested. Furthermore, seven weekly 148 µg doses ICV reduced those markers to near normal and produced a 99.5% reduction in HS-NRE levels. A pilot study utilizing every other week dosing in two animals supports further evaluation of less frequent dosing. Finally, our dose-response study also suggests lower doses may be efficacious. Our findings show that rhSGSH can normalize lysosomal HS storage and markers of a neuroimmune response when delivered ICV.

A cross-sectional study of hepatitis C prevalence and correlates among persons who inject drugs in rural and non-rural communities.

Persons who inject drugs (PWID) have been experiencing a higher burden of new hepatitis C (HCV) due to the opioid epidemic. The greatest increases in injection have been in rural communities. However, less is known about the prevalence of HCV or its risk factors in rural compared to non-rural communities. This study compared HCV infection history, current infection, and associated behavioural and sociodemographic correlates among PWID recruited from rural and non-rural communities from Upstate New York (NY). This cross-sectional study recruited 309 PWID, using respondent-driven sampling. Blood samples were collected through finger stick for HCV antibody and RNA tests. A survey was also self-administered for HCV infection history, sociodemographics and behavioural correlates to compare by setting rurality. HCV seropositivity was significantly higher among PWID from rural than non-rural communities (71.0% vs. 46.8%), as was current infection (41.4% vs. 25.9%). High levels of past year syringe (44.4%) and equipment (62.2%) sharing were reported. Factors associated with infection history include syringe service program utilization, non-Hispanic white race, sharing needles and methamphetamine injection, which was higher in rural vs. non-rural communities (38.5% vs. 15.5%). HCV burden among PWID appears higher in rural than non-rural communities and may be increasing possibly due to greater levels of methamphetamine injection. On-going systematic surveillance of HCV prevalence and correlates is crucial to respond to the changing opioid epidemic landscape. Additionally, improving access to harm reduction services, especially with special focus on stimulants, may be important to reduce HCV prevalence among PWID in rural settings.

Utility of Newborn Dried Blood Spots to Ascertain Seroprevalence of SARS-CoV-2 Antibodies Among Individuals Giving Birth in New York State, November 2019 to November 2021.

Importance: Serosurveys can be used to monitor population-level dynamics of COVID-19 and vaccination. Dried blood spots (DBSs) collected from infants contain maternal IgG antibodies and are useful for serosurveys of individuals recently giving birth. Objectives: To examine SARS-CoV-2 antibody prevalence in pregnant individuals in New York State, identify associations between SARS-CoV-2 antibody status and maternal and infant characteristics, and detect COVID-19 vaccination among this population. Design, Setting, and Participants: A population-based, repeated cross-sectional study was conducted to detect SARS-CoV-2 nucleocapsid (N) and spike (S) IgG antibodies. Deidentified DBS samples and data submitted to the New York State Newborn Screening Program between November 1, 2019, and November 30, 2021, were analyzed. Exposures: Prenatal exposure to SARS-CoV-2 antibodies. Main Outcomes and Measures: The presence of IgG antibodies to SARS-CoV-2 N and S antigens was measured using a microsphere immunoassay. Data were analyzed by geographic region and compared with reported COVID-19 cases and vaccinations among reproductive-aged females (15-44 years of age). Data were stratified by infant birth weight, gestational age, maternal age, and multiple birth status. Results: Dried blood spot samples from 415 293 infants (median [IQR] age, 1.04 [1.00-1.20] days; 210 805 [51.1%] male) were analyzed for SARS-CoV-2 antibodies. The first known antibody-positive infant in New York State was born on March 29, 2020. SARS-CoV-2 seroprevalence reflected statewide and regional COVID-19 cases among reproductive-aged females in the prevaccine period. From February through November 2021, S seroprevalence was strongly correlated with cumulative vaccinations in each New York State region and in the state overall (rs = 0.92-1.00, P ≤ .001). S and N seroprevalences were significantly lower in newborns with very low birth weight (720 [14.8%] for S and 138 [2.8%] for N, P < .001) and low birth weight (5160 [19.3%] for S and 1233 [4.6%] for N, P = .009) compared with newborns with normal birth weight (77 116 [20.1%] for S and 19 872 [5.2%] for N). Lower N and higher S seroprevalences were observed in multiple births (odds ratio [OR], 0.84; 95% CI, 0.75-0.94; P = .002 for N and OR, 1.24; 95% CI, 1.18-1.31; P < .001 for S) vs single births and for maternal age older than 30 years (OR, 0.87; 95% CI, 0.80-0.94; P < .001 for N and OR, 1.17; 95% CI, 1.11-1.23; P < .001 for S) vs younger than 20 years. Conclusions and Relevance: In this study, seroprevalence in newborn DBS samples reflected COVID-19 case fluctuations and vaccinations among reproductive-aged women during the study period. These results demonstrate the utility of using newborn DBS testing to estimate SARS-CoV-2 seroprevalence in pregnant individuals.

The Advisory Group on Risk Evidence Education for Dementia: Multidisciplinary and Open to All.

The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one's biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.

Patients asking about APOE gene test results? Here's what to tell them.

This guidance can help shape the conversations you have with patients who want to understand the results of their gene and biomarker testing for Alzheimer disease.

BRAF inhibitors and their immunological effects in malignant melanoma.

INTRODUCTION: The treatment of cutaneous melanoma has been revolutionized by the development of small-molecule inhibitors targeting the MAPK pathway, including inhibitors of BRAF (BRAFi) and MEK (MEKi), and immune checkpoint blockade antibodies, occurring in tandem. Despite these advances, the 5-year survival rate for patients with advanced melanoma remains only around 50%. Although not designed to alter immune responses within the tumor microenvironment (TME), MAPK pathway inhibitors (MAPKi) exert a range of effects on the host immune compartment that may offer opportunities for therapeutic interventions. AREAS COVERED: We review the effects of MAPKi, especially BRAFi, on the TME, focusing on alterations in inflammatory cytokine secretion, recruitment of immune cells and their functions, both during response to BRAFi treatment and as resistance develops. We outline potential combinations of MAPKi with established and experimental treatments. EXPERT OPINION: MAPKi in combination or in sequence with established treatments such as checkpoint inhibitors, anti-angiogenic agents, or new therapies such as adoptive cell therapies, may augment their immunological effects, reverse tumor-associated immune suppression, and offer the prospect of longer-lived clinical responses. Refining therapeutic tools at our disposal and embracing 'old friends' in the melanoma treatment arsenal, alongside new target identification, may improve the chances of therapeutic success.

Postpartum Mother-To-Child Transmission of HIV in a Breastfeeding Infant.

This article is an examination of MTCT of HIV through breastfeeding in a mother who seroconverted postnatally.

Phylogenetic Distribution of Ralstonia solanacearum Species Complex Populations in Potato in Kenya.

Ralstonia solanacearum is a pathogen causing bacterial wilt disease of potato, resulting in 70% potato production losses in Kenya. A study was conducted to determine the diversity of R. solanacearum species complex strains within the main potato-growing regions of Kenya. Potato tubers were collected in different potato-growing regions of Kenya from visibly wilted potato plants as well as samples of tomato, irrigation water, and cultures for pathogen isolation. Genomic DNA was isolated from 135 purified cultures of RSSC isolates and PCR-amplified using multiplex and sequevar primers targeting the endoglucanase (egl) partial gene sequences. Pathogenicity tests using R. solanacearum strain (phylotype II sequevar I) were done on the cultivars Kenya Karibu, Shangi, Chulu, Wanjiku, and MoneyMaker. Phylogenetic analysis of the partial egl gene identified two genospecies, R. pseudosolanacearum sp. nov. (1.5%) and R. solanacearum (98.5%). All R. solanacearum strains clustered in sequevar I and were distributed in all the potato-growing regions surveyed. The cultivars were grown in a greenhouse for two cycles in a randomized complete block design and inoculated with R. solanacearum strain. The severity scores were assessed and the area under the disease progress curve (AUDPC) was determined. All the cultivars tested for pathogenicity exhibited wilting symptoms at varying intervals after infection, with none showing complete resistance to R. solanacearum. Cultivar Shangi exhibited minimum disease severity and progression of 41.14% and AUDPC of 1041.7, respectively, while 'Kenya Karibu' was the most susceptible with a high progression rate of 68.24% and AUDPC of 1897.5, respectively. 'MoneyMaker', 'Chulu', and 'Wanjiku' showed no significant difference in disease severity, depicting a simultaneous rate of infection among them. These findings provide valuable information to better understand the pathogen genetic diversity in Kenya and how it spreads.

Examination of the reliability and feasibility of two smartphone applications to assess executive functioning in racially diverse older adults.

Inclusion of Black participants in clinical research is a national priority. Mobile applications and remote data collection may increase study access for diverse populations. This study examined the reliability and feasibility of two mobile smartphone application-based cognitive measures in a diverse middle aged and older adult sample. Black (n = 44; Mage = 59.93) and non-Hispanic white (NHW; n = 50; Mage = 61.06) participants completed traditional paper-based neuropsychological testing and two app-based measures, Arrows and Number Match. Intraclass correlations demonstrated poor to moderate reliability (range: .417-.569) between performance on the app-based versions and performance on the traditional versions. Performance score differences by racial group were not statistically significant. Both Black and NHW participants rated the app-based measures as feasible and acceptable, though Black participants endorsed a stronger likelihood of future use. These findings add to the growing literature on remote cognitive testing .

Reduced care burden and improved quality of life in African American family caregivers: Positive impact of personalized assistive technology.

BACKGROUND: African Americans living with dementia are considered less likely to seek formal institutionalized elder care and more likely to be managed in the home by family-member caregivers. Assistive technologies (the use of smart visual devices like tablets and phones) can be used effectively to guide memory-impaired individuals with a sequence of pictures showing steps to complete activities of daily living, e.g., bathing, toileting, dressing. Assistive technology so far has not been generally embraced in African American communities. OBJECTIVES: Determine, if African American family caregivers, given the opportunity, would embrace the use of assistive technology and if they would perceive its use beneficial. METHODS: We assessed a group of eight family caregivers' overall care-burden scores, and their user-satisfaction scores after using assistive technology for three months. RESULTS: We found significant reduction in caregiver burden, positive changes in behavior and emotion scores, and high ratings on user satisfaction. CONCLUSIONS: The findings reported here comprise the first systematic study of the use of assistive technology by caregivers in an underserved population. They set the stage for exploring meaningful strategies and variables that will better engage underserved populations to take advantage of assistive technologies available in healthcare.

Personalized Visual Mapping Assistive Technology to Improve Functional Ability in Persons With Dementia: Feasibility Cohort Study.

BACKGROUND: Mobile health (mHealth) apps using novel visual mapping assistive technology can allow users to develop personalized maps that aid people living with cognitive impairment in the recall of steps needed to independently complete activities of daily living (ADLs), such as bathing, toileting, and dressing. OBJECTIVE: This study aims to determine the feasibility and preliminary impact of an mHealth assistive technology app providing guidance to aid individuals living with cognitive impairment in the recall of steps to independently complete ADLs. METHODS: A total of 14 Veterans (mean age 65 SD 9.5 years; 14/14, 100% male; 10/14, 71.4% Black) and 8 non-Veterans (mean age 78, SD 10.3 years; 5/8, 62.5% male; 8/8, 100% Black) were recruited and enrolled from the Department of Veterans Affairs (VA) and non-VA cognitive care clinics. A visual mapping software program, MapHabit, was used to generate a series of personalized visual map templates focused on ADLs created within the MapHabit app. The visual maps were accessed through a tablet device. A 19-item exit questionnaire was administered to the participants to assess perceived improvement in their functional ability after using the MapHabit system for 3 months. RESULTS: A total of 13 (93%) VA clinic participants and 8 (100%) non-VA clinic participants completed the 3-month study. Baseline cognitive testing indicated impaired to significantly impaired cognitive function. After 3 months of using the MapHabit system, VA clinic participants reported perceived improvement in social engagement (P=.01) and performance of ADLs (P=.05) compared to the baseline, whereas non-VA clinic participants reported improvements in the performance of ADLs (P=.02), mood (P=.04), social engagement (P=.02), and memory (P=.02). All study participants reported they would recommend the MapHabit system to a colleague, and 85% (11/14) of VA and 100% (8/8) of non-VA clinic participants reported a willingness to participate in a future study. CONCLUSIONS: Older VA and non-VA clinic participants with cognitive impairment were willing to use an mHealth app to assist with the completion of ADLs, and they reported positive preliminary effects. A larger study is warranted to assess the efficacy in the setting of a randomized controlled trial.

High-Throughput Multiplex SARS-CoV-2 IgG Microsphere Immunoassay for Dried Blood Spots: A Public Health Strategy for Enhanced Serosurvey Capacity.

Early in the pandemic when diagnostic testing was not widely available, serosurveys played an important role in estimating the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations. Dried blood spots (DBS), which can be collected in nonclinical settings, provide a minimally invasive alternative to serum for serosurveys. We developed a Luminex-based SARS-CoV-2 microsphere immunoassay (MIA) for DBS that detects IgG antibodies to nucleocapsid (N) and spike subunit 1 (S1) antigens. The assay uses a 384-well plate format and automated liquid handlers for high-throughput capacity. Specificity was assessed using a large collection of prepandemic DBS and well-characterized sera. Sensitivity was analyzed using serology data from New York State SARS-CoV-2 serosurvey testing and matched diagnostic test results. For DBS, the specificity was 99.5% for the individual N and S1 antigens. Median fluorescence intensity (MFI) values for DBS and paired sera showed a strong positive correlation for N (R2 = 0.91) and S1 (R2 = 0.93). Sensitivity, assessed from 1,134 DBS with prior laboratory-confirmed SARS-CoV-2 infection, ranged from 83% at 0 to 20 days to 95% at 61 to 90 days after a positive test. When stratified using coronavirus disease 2019 (COVID-19) symptom data, sensitivity ranged from 90 to 96% for symptomatic and 77 to 91% for asymptomatic individuals. For 8,367 health care workers reporting detailed symptom data, MFI values were significantly higher for all symptom categories. Our results indicate that the SARS-CoV-2 IgG DBS MIA is sensitive, specific, and well-suited for large population-based serosurveys. The ability to readily modify and multiplex antigens is important for ongoing assessment of SARS-CoV-2 antibody responses to emerging variants and vaccines. IMPORTANCE Testing for antibodies to SARS-CoV-2 has been used to estimate the prevalence of COVID-19 in different populations. Seroprevalence studies, or serosurveys, were especially useful during the early phase of the pandemic when diagnostic testing was not widely available, and the resulting seroprevalence estimates played an important role in public health decision making. To achieve meaningful results, antibody tests used for serosurveys should be accurate and accessible to diverse populations. We developed a test that detects antibodies to two different SARS-CoV-2 proteins in dried blood spots (DBS). DBS require only a simple fingerstick and can be collected in nonclinical settings. We conducted a robust validation study and have demonstrated that our test is both sensitive and specific. Furthermore, we demonstrated that our test is suitable for large-scale serosurveys by testing over 56,000 DBS collected in a variety of community-based venues in New York State during the spring of 2020.

A review of varietal change in roots, tubers and bananas: consumer preferences and other drivers of adoption and implications for breeding.

This review of the literature on varietal change in sub-Saharan Africa looks in detail at adoption of new varieties of bananas in Uganda, cassava in Nigeria, potato in Kenya, sweetpotato in Uganda and yams in Côte d'Ivoire. The review explored three hypotheses about drivers of varietal change. There was a strong confirmation for the hypothesis that insufficient priority given to consumer-preferred traits by breeding programmes contributes to the limited uptake of modern varieties (MVs) and low varietal turnover. Lack of evidence meant the second hypothesis of insufficient attention to understanding and responding to gender differences in consumer preferences for quality and post-harvest traits was unresolved. The evidence on the third hypothesis about the informal seed system contributing to slow uptake of MVs was mixed. In some cases, the informal system has contributed to rapid uptake of MVs, but often it appears to be a barrier with inconsistent varietal naming a major challenge.

Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) received an Emergency Use Authorization by the US Food and Drug Administration (FDA). CCP with a signal-to-cutoff ratio of ≥12 using the Ortho VITROS severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) test (OVSARS2IgG) is permitted to be labeled "high titer." Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2. METHODS: Nine hundred eighty-one samples from 196 repeat CCP donors 0-119 days post-initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations was evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy. RESULTS: Of donations, 32.7%/79.5% (PRNT90/PRNT50) met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cutoff ≥85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of ≥1:640 (PRNT50) and/or ≥1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cutoff. CONCLUSIONS: This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.

Molecular Diversity and Pathogenicity of Ralstonia solanacearum Species Complex Associated With Bacterial Wilt of Potato in Rwanda.

Bacterial wilt (BW), caused by Ralstonia solanacearum species complex (RSSC), leads to substantial potato yield losses in Rwanda. Studies were conducted to (i) determine the molecular diversity of RSSC strains associated with BW of potato, (ii) generate an RSSC distribution map for epidemiological inferences, and (iii) test the pathogenicity of predominant RSSC phylotypes on six commercial potato cultivars. In surveys conducted in 2018 and 2019, tubers from wilting potato plants were collected for pathogen isolation. DNA was extracted from 95 presumptive RSSC strain colonies. The pathogen was phylotyped by multiplex PCR and typed at sequevar level. Phylotype II sequevar 1 strains were then haplotyped using multilocus tandem repeat sequence typing (TRST) schemes. Pathogenicity of one phylotype II strain and two phylotype III strains were tested on cultivars Kinigi, Kirundo, Victoria, Kazeneza, Twihaze, and Cruza. Two RSSC phylotypes were identified, phylotype II (95.79%, n = 91) and phylotype III (4.21%, n = 4). This is the first report of phylotype III strains from Rwanda. Phylotype II strains were identified as sequevar 1 and distributed across potato growing regions in the country. The TRST scheme identified 14 TRST haplotypes within the phylotype II sequevar 1 strains with moderate diversity index (HGDI = 0.55). Mapping of TRST haplotypes revealed that a single TRST '8-5-12-7-5' haplotype plays an important epidemiological role in BW of potato in Rwanda. None of the cultivars had complete resistance to the tested phylotypes; the level of susceptibility varied among cultivars. Cultivar Cruza, which is less susceptible to phylotype II and III strains, is recommended when planting potatoes in the fields with history of BW.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores.

INTRODUCTION: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1. METHODS: First, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared receiver-operating characteristic (ROC) area under the curve in differentiating CDRs for the remaining tests. RESULTS: Some V3 tests performed better than V2 tests in differentiating between CDR 0.5 and 0, but the improvement was limited to Caucasian participants. DISCUSSION: Further efforts to improve the ability for early identification of cognitive decline among diverse racial groups are required.