Do the benefits of homeownership on mental health vary by race and poverty status? An application of doubly robust estimation for causal inference.

While empirical studies have observed that homeownership is associated with improved mental health conditions, research indicates that this relationship might vary by race. Moreover, such a White-Black disparity in the impacts of homeownership on mental health could be complexed by poverty status, as maintaining one's homeownership could be a financial burden for people living in poverty status, defined by the US official poverty threshold. We add to the existing literature by analyzing the impacts of homeownership on psychological distress, simultaneously disaggregating by race and poverty status using survey data from the Panel Study on Income Dynamics from the 2017 and 2019 waves (N = 7059). Propensity score weighting and doubly robust estimation are applied to estimate causal inference for the impact of 2017 homeownership on 2019 psychological distress using negative binomial models. First, we found the impacts of homeownership on reducing psychological distress are significant for White Americans, not for Black Americans. Second, we found such a White-Black disparity is only observable for populations not living in poverty. On the other hand, for populations living in poverty, homeownership no longer lowers psychological distress for either race. Findings suggest that financial support and mental health support are needy to address inequality in the impacts of homeownership on mental health, which could simultaneously vary by poverty status and race. Implications are discussed.

The auxin efflux carrier PIN1a regulates vascular patterning in cereal roots.

Barley (Hordeum vulgare) is an important global cereal crop and a model in genetic studies. Despite advances in characterising barley genomic resources, few mutant studies have identified genes controlling root architecture and anatomy, which plays a critical role in capturing soil resources. Our phenotypic screening of a TILLING mutant collection identified line TM5992 exhibiting a short-root phenotype compared with wild-type (WT) Morex background. Outcrossing TM5992 with barley variety Proctor and subsequent SNP array-based bulk segregant analysis, fine mapped the mutation to a cM scale. Exome sequencing pinpointed a mutation in the candidate gene HvPIN1a, further confirming this by analysing independent mutant alleles. Detailed analysis of root growth and anatomy in Hvpin1a mutant alleles exhibited a slower growth rate, shorter apical meristem and striking vascular patterning defects compared to WT. Expression and mutant analyses of PIN1 members in the closely related cereal brachypodium (Brachypodium distachyon) revealed that BdPIN1a and BdPIN1b were redundantly expressed in root vascular tissues but only Bdpin1a mutant allele displayed root vascular defects similar to Hvpin1a. We conclude that barley PIN1 genes have sub-functionalised in cereals, compared to Arabidopsis (Arabidopsis thaliana), where PIN1a sequences control root vascular patterning.

The evolution of the duckweed ionome mirrors losses in structural complexity.

BACKGROUND AND AIMS: The duckweeds (Lemnaceae) consist of 36 species exhibiting impressive phenotypic variation, including the progressive evolutionary loss of a fundamental plant organ, the root. Loss of roots and reduction of vascular tissues in recently derived taxa occur in concert with genome expansions of ≤14-fold. Given the paired loss of roots and reduction in structural complexity in derived taxa, we focus on the evolution of the ionome (whole-plant elemental contents) in the context of these fundamental changes in body plan. We expect that progressive vestigiality and eventual loss of roots might have both adaptive and maladaptive consequences that are hitherto unknown. METHODS: We quantified the ionomes of 34 accessions in 21 species across all duckweed genera, spanning 70 Myr in this rapidly cycling plant (doubling times are as rapid as ~24 h). We related both micro- and macroevolutionary ionome contrasts to body plan remodelling and showed nimble microevolutionary shifts in elemental accumulation and exclusion in novel accessions. KEY RESULTS: We observed a robust directional trend in calcium and magnesium levels, decreasing from the ancestral representative Spirodela genus towards the derived rootless Wolffia, with the latter also accumulating cadmium. We also identified abundant within-species variation and hyperaccumulators of specific elements, with this extensive variation at the fine (as opposed to broad) scale. CONCLUSIONS: These data underscore the impact of root loss and reveal the very fine scale of microevolutionary variation in hyperaccumulation and exclusion of a wide range of elements. Broadly, they might point to trade-offs not well recognized in ionomes.

Psoas Muscle Area as a Predictor of Transcatheter Aortic Valve Implantation Outcomes.

BACKGROUND: Frailty is a well-recognised predictor of outcomes after transcatheter aortic valve implantation (TAVI). Psoas muscle area (PMA) is a surrogate marker for sarcopaenia and is a validated assessment tool for frailty. The objective of this study was to examine frailty as a predictor of outcomes in TAVI patients and assess the prognostic usefulness of adding PMA to established frailty assessments. METHODS: Frailty assessments were performed on 220 consecutive patients undergoing TAVI. These assessments used four markers (serum albumin, handgrip strength, gait speed, and a cognitive assessment), which were combined to form a composite frailty score. Preprocedural computed tomography scans were used to calculate cross-sectional PMA for each patient. The primary outcomes were all-cause mortality at 1-year and post-procedure length of hospital stay. RESULTS: Frailty status, as defined by the composite frailty score, was independently predictive of length of hospital stay (p=0.001), but not predictive of 1-year mortality (p=0.161). Albumin (p=0.036) and 5-metre walk test (p=0.003) were independently predictive of 1-year mortality. The PMA, when adjusted for gender, and normalised according to body surface area, was not predictive of 1-year mortality. Normalised PMA was associated with increased post-procedure length of stay within the female population (p=0.031). CONCLUSIONS: A low PMA is associated with increased length of hospital stay in female TAVI patients but does not provide additional predictive value over traditional frailty scores. The PMA was not shown to correlate with TAVI-related complications or 1-year mortality.

3-Methylglutarylcarnitine: A biomarker of mitochondrial dysfunction.

The acylcarnitines comprise a wide range of acyl groups linked via an ester bond to the hydroxyl group of L-carnitine. Mass spectrometry methods are capable of measuring the relative abundance of hundreds of acylcarnitines in a single drop of blood. As such, acylcarnitines can serve as sensitive biomarkers of disease. For certain acylcarnitines, however, their biochemical origin, and biomedical significance, remain unclear. One such example is 3-methylglutaryl (3MG) carnitine (C5-3M-DC). Whereas 3MG carnitine levels are normally very low, elevated levels are detected in discrete inborn errors of metabolism (IEM) as well as different forms of heart disease. Moreover, acute injury, including γ radiation exposure, paraquat poisoning, and traumatic brain injury manifest elevated levels of 3MG carnitine in blood and/or urine. Recent evidence indicates that two distinct biosynthetic routes to 3MG carnitine exist. The first, caused by an inherited deficiency in the leucine catabolism pathway enzyme, 3-hydroxy-3-methylglutaryl (HMG) CoA lyase, leads to a buildup of trans-3-methylglutaconyl (3MGC) CoA. Reduction of the double bond in trans-3MGC CoA generates 3MG CoA, which is then converted to 3MG carnitine by carnitine acyltransferase. This route, however, cannot explain why 3MG carnitine levels increase in IEMs that do not affect leucine metabolism or various chronic and acute disease states. In these cases, disease-related defects in aerobic energy metabolism result in diversion of acetyl CoA to trans-3MGC CoA. Once formed, trans-3MGC CoA is reduced to 3MG CoA and esterified to form 3MG carnitine. Thus, 3MG carnitine, represents a potential biomarker of disease processes associated with compromised mitochondrial energy metabolism.

Child Protective Services Reports After Reunification: An Examination of the Risk of Being Rereported to Child Protective Services After Returning Home From Foster Care.

While a number of studies have examined the risk of reentry after exiting foster care, few studies have examined the risk of rereport to Child Protective Services (CPS) in the United States. Understanding more about rereports may help identify targets for supportive services that prevent reentry and promote safety. This study is the first to use nation-wide linked data to examine the risk of rereport for reunified children. The sample included children reunified after experiencing their first episode in foster care with at least one CPS report prior to care. With a 2000-day observation period, flexible parametric survival models with time varying hazard ratios were used to model the hazard or rereport conditional on prior CPS and foster care characteristics. Over 50% of the sample experienced a rereport after reunification. Results indicate that children entering foster care following a history of multiple CPS reports prior to placement were at substantially increased risk of rereport after returning home. A group of children with shorter stays in care had a high risk of recurrence within the first month, but this was not true over time. Implications for future research as well as permanency planning and addressing the needs of families with chronic reports are discussed.

C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption.

While the toxicity of PARP inhibitors to cells with defects in homologous recombination (HR) is well established, other synthetic lethal interactions with PARP1/PARP2 disruption are poorly defined. To inform on these mechanisms we conducted a genome-wide screen for genes that are synthetic lethal with PARP1/2 gene disruption and identified C16orf72/HAPSTR1/TAPR1 as a novel modulator of replication-associated R-loops. C16orf72 is critical to facilitate replication fork restart, suppress DNA damage and maintain genome stability in response to replication stress. Importantly, C16orf72 and PARP1/2 function in parallel pathways to suppress DNA:RNA hybrids that accumulate at stalled replication forks. Mechanistically, this is achieved through an interaction of C16orf72 with BRCA1 and the RNA/DNA helicase Senataxin to facilitate their recruitment to RNA:DNA hybrids and confer resistance to PARP inhibitors. Together, this identifies a C16orf72/Senataxin/BRCA1-dependent pathway to suppress replication-associated R-loop accumulation, maintain genome stability and confer resistance to PARP inhibitors.

Acidification of previously limed upland pastures - An overlooked flood risk factor?

In low-lying land, the impact of agriculture on flooding has focussed on soil compaction, whilst in the uplands there has been more interest in the influence of afforestation. The potential effect of acidification of previously limed upland grassland soils on this risk has been overlooked. The marginal economics of upland farms has led to inadequate lime application on these grasslands. In Wales, UK, agronomic improvement of upland acid grasslands with liming was widespread in the last century. The extent and topographical distribution of this land use in Wales was estimated and these characteristics were mapped in four catchments studied in more detail. Then 41 sites on improved pastures within the catchments were sampled, where lime had not been applied for periods of between two and 30 years; unimproved acid pastures adjacent to five of these sites were also sampled. Soil pH, organic matter, infiltration rates and earthworm populations were recorded. Grasslands at risk of acidification without maintenance liming were estimated to cover almost 20 % of upland Wales. The majority of these grasslands were located on steeper slopes (gradients >7o) where any reduction in infiltration would promote surface runoff and limit rainwater retention. The extent of these pastures varied markedly between the four study catchments. There was a 6-fold reduction in infiltration rates between high and low pH soils, and this trend was correlated with reductions in anecic earthworm abundance. The vertical burrows of these earthworms are important for infiltration and no such earthworms were present in the most acidic soils. Recently limed soils had infiltration rates similar to those of unimproved acid pastures. Soil acidification has the potential to exacerbate flood risk but further research is needed to assess the extent of any impact. Modelling of catchment specific flood risk should include the extent of upland soil acidification as an additional land use factor.

Loss of ancestral function in duckweed roots is accompanied by progressive anatomical reduction and a re-distribution of nutrient transporters.

Organ loss occurs frequently during plant and animal evolution. Sometimes, non-functional organs are retained through evolution. Vestigial organs are defined as genetically determined structures that have lost their ancestral (or salient) function.1,2,3 Duckweeds, an aquatic monocot family, exhibit both these characteristics. They possess a uniquely simple body plan, variably across five genera, two of which are rootless. Due to the existence of closely related species with a wide diversity in rooting strategies, duckweed roots represent a powerful system for investigating vestigiality. To explore this, we employed a panel of physiological, ionomic, and transcriptomic analyses, with the main goal of elucidating the extent of vestigiality in duckweed roots. We uncovered a progressive reduction in root anatomy as genera diverge and revealed that the root has lost its salient ancestral function as an organ required for supplying nutrients to the plant. Accompanying this, nutrient transporter expression patterns have lost the stereotypical root biased localization observed in other plant species. While other examples of organ loss such as limbs in reptiles4 or eyes in cavefish5 frequently display a binary of presence/absence, duckweeds provide a unique snapshot of an organ with varying degrees of vestigialization in closely related neighbors and thus provide a unique resource for exploration of how organs behave at different stages along the process of loss.

Racial/Ethnic Differences in Child Protective Services Reporting, Substantiation and Placement, With Comparison to Non-CPS Risks and Outcomes: 2005-2019.

We used National Child Abuse and Neglect Data System and Census data to examine Black-White and Hispanic-White disparities in reporting, substantiation, and out-of-home placement both descriptively from 2005-2019 and in multivariate models from 2007-2017. We also tracked contemporaneous social risk (e.g., child poverty) and child harm (e.g., infant mortality) disparities using non-child protective services (CPS) sources and compared them to CPS reporting rate disparities. Black-White CPS reporting disparities were lower than found in non-CPS risk and harm benchmarks. Consistent with the Hispanic paradox, Hispanic-White CPS reporting disparities were lower than risk disparities but similar to harm disparities. Descriptive and multivariate analyses of data from the past several years indicated that Black children were less likely to be substantiated or placed into out-of-home care following a report than White children. Hispanic children were slightly more likely to be substantiated or placed in out-of-home care than White children overall, but this difference disappeared in multivariate models. Available data provide no evidence that Black children were overreported relative to observed risks and harms reflected in non-CPS data. Reducing reporting rates among Black children will require addressing broader conditions associated with maltreatment.

Overexpressing Vitamin C Defective 2 reduces fertility and alters Ca2+ signals in Arabidopsis pollen.

A potential strategy to mitigate oxidative damage in plants is to increase the abundance of antioxidants, such as ascorbate (i.e. vitamin C). In Arabidopsis (A. thaliana), a rate-limiting step in ascorbate biosynthesis is a phosphorylase encoded by Vitamin C Defective 2 (VTC2). To specifically overexpress VTC2 (VTC2 OE) in pollen, the coding region was expressed using a promoter from a gene with ∼150-fold higher expression in pollen, leading to pollen grains with an eight-fold increased VTC2 mRNA. VTC2 OE resulted in a near-sterile phenotype with a 50-fold decrease in pollen transmission efficiency and a five-fold reduction in the number of seeds per silique. In vitro assays revealed pollen grains were more prone to bursting (greater than two-fold) or produced shorter, morphologically abnormal pollen tubes. The inclusion of a genetically encoded Ca2+ reporter, mCherry-GCaMP6fast (CGf), revealed pollen tubes with altered tip-focused Ca2+ dynamics and increased bursting frequency during periods of oscillatory and arrested growth. Despite these phenotypes, VTC2 OE pollen failed to show expected increases in ascorbate or reductions in reactive oxygen species, as measured using a redox-sensitive dye or a roGFP2. However, mRNA expression analyses revealed greater than two-fold reductions in mRNA encoding two enzymes critical to biosynthetic pathways related to cell walls or glyco-modifications of lipids and proteins: GDP-d-mannose pyrophosphorylase (GMP) and GDP-d-mannose 3',5' epimerase (GME). These results support a model in which the near-sterile defects resulting from VTC2 OE in pollen are associated with feedback mechanisms that can alter one or more signaling or metabolic pathways critical to pollen tube growth and fertility.

Repurposing FDA-approved drugs as inhibitors of therapy-induced invadopodia activity in glioblastoma cells.

Glioblastoma (GBM) is the most prevalent primary central nervous system tumour in adults. The lethality of GBM lies in its highly invasive, infiltrative, and neurologically destructive nature resulting in treatment failure, tumour recurrence and death. Even with current standard of care treatment with surgery, radiotherapy and chemotherapy, surviving tumour cells invade throughout the brain. We have previously shown that this invasive phenotype is facilitated by actin-rich, membrane-based structures known as invadopodia. The formation and matrix degrading activity of invadopodia is enhanced in GBM cells that survive treatment. Drug repurposing provides a means of identifying new therapeutic applications for existing drugs without the need for discovery or development and the associated time for clinical implementation. We investigate several FDA-approved agents for their ability to act as both cytotoxic agents in reducing cell viability and as 'anti-invadopodia' agents in GBM cell lines. Based on their cytotoxicity profile, three agents were selected, bortezomib, everolimus and fludarabine, to test their effect on GBM cell invasion. All three drugs reduced radiation/temozolomide-induced invadopodia activity, in addition to reducing GBM cell viability. These drugs demonstrate efficacious properties warranting further investigation with the potential to be implemented as part of the treatment regime for GBM.

Resilience of ecosystem service delivery in grasslands in response to single and compound extreme weather events.

Extreme weather events are increasing in frequency and magnitude with profound effects on ecosystem functioning. Further, there is now a greater likelihood that multiple extreme events are occurring within a single year. Here we investigated the effect of a single drought, flood or compound (flood + drought) extreme event on temperate grassland ecosystem processes in a field experiment. To assess system resistance and resilience, we studied changes in a wide range of above- and below-ground indicators (plant diversity and productivity, greenhouse gas emissions, soil chemical, physical and biological metrics) during the 8 week stress events and then for 2 years post-stress. We hypothesized that agricultural grasslands would have different degrees of resistance and resilience to flood and drought stress. We also investigated two alternative hypotheses that the combined flood + drought treatment would either, (A) promote ecosystem resilience through more rapid recovery of soil moisture conditions or (B) exacerbate the impact of the single flood or drought event. Our results showed that flooding had a much greater effect than drought on ecosystem processes and that the grassland was more resistant and resilient to drought than to flood. The immediate impact of flooding on all indicators was negative, especially for those related to production, and climate and water regulation. Flooding stress caused pronounced and persistent shifts in soil microbial and plant communities with large implications for nutrient cycling and long-term ecosystem function. The compound flood + drought treatment failed to show a more severe impact than the single extreme events. Rather, there was an indication of quicker recovery of soil and microbial parameters suggesting greater resilience in line with hypothesis (A). This study clearly reveals that contrasting extreme weather events differentially affect grassland ecosystem function but that concurrent events of a contrasting nature may promote ecosystem resilience to future stress.

Testing a QuantCrit-Informed Approach to the Empirical Study of Race/Ethnicity and Child Maltreatment.

The past several years have seen calls from QuantCrit scholars to "disaggregate" samples into same-race groups. To date, however, there has been no attempt to empirically evaluate the benefits of disaggregation within a child welfare sample. Using a child maltreatment dataset derived from the National Child Abuse and Neglect Data System and Census data, we empirically evaluate the utility of employing sample disaggregation (in which separate records are created for White, Black and Latino populations in each county) as well as variable creation disaggregation (in which we avoid using "full county" economic measures, but instead employ "same race/ethnicity" measures). Using model fit and convergence with findings from individual-level studies as evaluation metrics, we find that both kinds of disaggregation are demonstrably beneficial. We recommend that sample and variable disaggregation be considered by any future researchers using national geographically structured child maltreatment data.

Wearable Devices in Veterinary Health Care.

Wearables are an up-and-coming tool in veterinary health care. This article reviews the current and prospective wearable technology for veterinary patients and the future of wearables in veterinary medicine. These devices allow veterinarians to monitor a patient's vital signs remotely, in addition to other variables, and push the profession away from a reactive health-care system toward a proactive culture that is able to identify diseases earlier. Advances in this technology have the potential to profoundly change the way veterinarians obtain and use patient data to practice medicine.

Latitudinal gradient in species diversity provides high niche opportunities for a range-expanding phytophagous insect.

When species undergo poleward range expansions in response to anthropogenic change, they likely encounter less diverse communities in new locations. If low diversity communities provide weak biotic interactions, such as reduced competition or predation, range-expanding species may experience high niche opportunities. Here, we investigated if oak gall wasp communities follow a latitudinal diversity gradient (LDG) and if lower diversity communities provide weaker interactions at the poles for a range-expanding community member, Neuroterus saltatorius. We performed systematic surveys of gall wasps on a dominant oak, Quercus garryana, throughout most of its range, from northern California to Vancouver Island, British Columbia. On 540 trees at 18 sites, we identified 23 oak gall wasp morphotypes in three guilds (leaf detachable, leaf integral, and stem galls). We performed regressions between oak gall wasp diversity, latitude, and other abiotic (e.g. temperature) and habitat (e.g. oak patch size) factors to reveal if gall wasp communities followed an LDG. To uncover patterns in local interactions, we first performed partial correlations of gall wasp morphotype occurrences on trees within regions). We then performed regressions between abundances of co-occurring gall wasps on trees to reveal if interactions are putatively competitive or antagonistic. Q. garryana-gall wasp communities followed an LDG, with lower diversity at higher latitudes, particularly with a loss of detachable leaf gall morphotypes. Detachable leaf gall wasps, including the range-expanding species, co-occurred most on trees, with weak co-occurrences on trees in the northern expanded region. Abundances of N. saltatorius and detachable and integral leaf galls co-occurring on trees were negatively related, suggesting antagonistic interactions. Overall, we found that LDGs create communities with weaker associations at the poles that might facilitate ecological release in a range-expanding community member. Given the ubiquity of LDGs in nature, poleward range-expanding species are likely moving into low diversity communities. Yet, understanding if latitudinal diversity pattern provides weak biotic interactions for range-expanding species is not well explored. Our large-scale study documenting diversity in a related community of phytophagous insects that co-occur on a host plant reveals that LDGs create high niche opportunities for a range-expanding community member. Biogeographical patterns in diversity and species interactions are likely important mechanisms contributing to altered biotic interactions under range-expansions.

Cuando las especies se expanden hacia los polos en respuesta al cambio antropogénico, es probable que las encuentren comunidades menos diversas en sus nuevos lugares. Si las comunidades de baja diversidad proporcionan interacciones bióticas débiles, como competencia reducida o depredación, las especies que se expanden pueden tener 'oportunidades de alto nicho'. Aquí, investigamos si las comunidades de avispas de las agallas muestran un gradiente de diversidad latitudinal (LDG) y si las comunidades de menor diversidad proporcionan interacciones antagónicas más débiles en los polos para las comunidades que se expanden. Específicamente, investigamos estas relaciones en la comunidad de Neuroterus saltatorius. Realizamos estudios sistemáticos de las avispas de las agallas en un roble dominante, Quercus garryana en la mayor parte de su área de distribución, desde el norte de California hasta la isla de Vancouver, en la Columbia Británica. Sobre 540 árboles en 18 sitios y 6 regiones, nos identificamos 23 mofotipos de avispas de las agallas en tres gremios (hoja desmontable, hoja integral y agallas del tallo). Ejecutamos regresiones entre la diversidad de avispas de las agallas, la latitud, y otros factores abióticos (p. ej., temperatura) y de hábitat (p. ej., tamaño del parche de roble) para revelar si las comunidades de avispas de las agallas siguieron un LDG. Para descubrir tendencias en las interacciones locales, primero ejecutamos correlaciones parciales de ocurrencias de morfotipos de avispas de las agallas en árboles dentro de las regiones. Luego ejecutamos regresiones entre las coocurrencias de las abundancias deavispas de las agallas en los árboles para revelar si las interacciones son supuestamente competitivas o antagónicas. Las comunidades de avispas Q. garryana-gall, siguieron un LDG, con menor diversidad en latitudes más altas, particularmente con una pérdida de morfotipos de agallas de hoja desmontable. Las avispas de las agallas de las hojas desprendibles, incluidas a las especies que se expanden su hábitat, se encontraron en sobre todos los árboles, con coocurrencias débiles en los árboles de la región expandida del norte. Las coocurrencias de las las abundancias de N. saltatorius,las agallas foliares desmontables, e agallas integrales en los árboles se relacionaron negativamente, lo que sugiere interacciones antagónicas. En general, encontramos que los LDG crean comunidades con asociaciones más débiles en los polos que podrían facilitar la liberación ecológica en un miembro de la comunidad que se expanden. Debido de la ubicuidad de los LDG en la naturaleza, es probable que las especies que se expanden hacia los polos se estén trasladando a comunidades de baja diversidad. Sin embargo, no se explora bien la comprensión de si las tendenciasde diversidad latitudinal proporcionan interacciones bióticas débiles para las especies que se expanden. Nuestro estudio degran escala documenta la diversidad en una comunidad relacionada de insectos fitófagos que coexisten en una planta hospedante. Como resultado, revela que los LDG pueden crear oportunidades de grandes nichos para un miembro de la comunidad que se expande. Los patrones biogeográficos en la diversidad y las interacciones entre especies son probablemente mecanismos importantes que contribuyen a las interacciones bióticas alteradas bajo la expansión del hábitat.

Use of Self-Collected Saliva Samples for the Detection of SARS-CoV-2.

OBJECTIVE: Using a US Food and Drug Administration (FDA) emergency use authorization (EUA) reverse transcription polymerase chain reaction (RT-PCR) method, we examined the analytic performance accuracy of saliva specimens as compared to nasopharyngeal (NP) specimens in symptomatic patients. Correlation between test results and symptoms was also evaluated. METHODS: Over a 5-week period in 2020, 89 matched saliva and nasopharyngeal swabs were collected from individuals exhibiting symptoms consistent with SARS-CoV-2. Specimens were tested with an FDA EUA-approved RT-PCR method, and performance characteristics were compared. RESULTS: The concordance rate between saliva and nasopharyngeal testing was 93.26%. The mean cycle threshold value of saliva when compared to the NP specimen was 3.56 cycles higher. As compared to NP swab, saliva testing demonstrates acceptable agreement but lower sensitivity. CONCLUSION: When compared to a reference method using NP swabs, the use of saliva testing proved to be a reliable method. Self-collected saliva testing for SARS-CoV-2 allows for a viable option when trained staff or collection materials are in short supply.

Diversion of Acetyl CoA to 3-Methylglutaconic Acid Caused by Discrete Inborn Errors of Metabolism.

A growing number of inborn errors of metabolism (IEM) have been identified that manifest 3-methylglutaconic (3MGC) aciduria as a phenotypic feature. In primary 3MGC aciduria, IEM-dependent deficiencies in leucine pathway enzymes prevent catabolism of trans-3MGC CoA. Consequently, this metabolite is converted to 3MGC acid and excreted in urine. In secondary 3MGC aciduria, however, no leucine metabolism pathway enzyme deficiencies exist. These IEMs affect mitochondrial membrane structure, electron transport chain function or ATP synthase subunits. As a result, acetyl CoA oxidation via the TCA cycle slows and acetyl CoA is diverted to trans-3MGC CoA, and then to 3MGC acid. Whereas the trans diastereomer of 3MGC CoA is the only biologically relevant diastereomer, the urine of affected subjects contains both cis- and trans-3MGC acids. Studies have revealed that trans-3MGC CoA is susceptible to isomerization to cis-3MGC CoA. Once formed, cis-3MGC CoA undergoes intramolecular cyclization, forming an anhydride that, upon hydrolysis, yields cis-3MGC acid. Alternatively, cis-3MGC anhydride can acylate protein lysine side chains. Once formed, cis-3MGCylated proteins can be deacylated by the NAD+-dependent enzyme, sirtuin 4. Taken together, the excretion of 3MGC acid in secondary 3MGC aciduria represents a barometer of defective mitochondrial function.