Eleven biosynthetic genes explain the majority of natural variation in carotenoid levels in maize grain.

Vitamin A deficiency remains prevalent in parts of Asia, Latin America, and sub-Saharan Africa where maize (Zea mays) is a food staple. Extensive natural variation exists for carotenoids in maize grain. Here, to understand its genetic basis, we conducted a joint linkage and genome-wide association study of the US maize nested association mapping panel. Eleven of the 44 detected quantitative trait loci (QTL) were resolved to individual genes. Six of these were correlated expression and effect QTL (ceeQTL), showing strong correlations between RNA-seq expression abundances and QTL allelic effect estimates across six stages of grain development. These six ceeQTL also had the largest percentage of phenotypic variance explained, and in major part comprised the three to five loci capturing the bulk of genetic variation for each trait. Most of these ceeQTL had strongly correlated QTL allelic effect estimates across multiple traits. These findings provide an in-depth genome-level understanding of the genetic and molecular control of carotenoids in plants. In addition, these findings provide a roadmap to accelerate breeding for provitamin A and other priority carotenoid traits in maize grain that should be readily extendable to other cereals.

A conserved genetic architecture among populations of the maize progenitor, teosinte, was radically altered by domestication.

Very little is known about how domestication was constrained by the quantitative genetic architecture of crop progenitors and how quantitative genetic architecture was altered by domestication. Yang et al. [C. J. Yang et al., Proc. Natl. Acad. Sci. U.S.A. 116, 5643-5652 (2019)] drew multiple conclusions about how genetic architecture influenced and was altered by maize domestication based on one sympatric pair of teosinte and maize populations. To test the generality of their conclusions, we assayed the structure of genetic variances, genetic correlations among traits, strength of selection during domestication, and diversity in genetic architecture within teosinte and maize. Our results confirm that additive genetic variance is decreased, while dominance genetic variance is increased, during maize domestication. The genetic correlations are moderately conserved among traits between teosinte and maize, while the genetic variance-covariance matrices (G-matrices) of teosinte and maize are quite different, primarily due to changes in the submatrix for reproductive traits. The inferred long-term selection intensities during domestication were weak, and the neutral hypothesis was rejected for reproductive and environmental response traits, suggesting that they were targets of selection during domestication. The G-matrix of teosinte imposed considerable constraint on selection during the early domestication process, and constraint increased further along the domestication trajectory. Finally, we assayed variation among populations and observed that genetic architecture is generally conserved among populations within teosinte and maize but is radically different between teosinte and maize. While selection drove changes in essentially all traits between teosinte and maize, selection explains little of the difference in domestication traits among populations within teosinte or maize.

Domestication reshaped the genetic basis of inbreeding depression in a maize landrace compared to its wild relative, teosinte.

Inbreeding depression is the reduction in fitness and vigor resulting from mating of close relatives observed in many plant and animal species. The extent to which the genetic load of mutations contributing to inbreeding depression is due to large-effect mutations versus variants with very small individual effects is unknown and may be affected by population history. We compared the effects of outcrossing and self-fertilization on 18 traits in a landrace population of maize, which underwent a population bottleneck during domestication, and a neighboring population of its wild relative teosinte. Inbreeding depression was greater in maize than teosinte for 15 of 18 traits, congruent with the greater segregating genetic load in the maize population that we predicted from sequence data. Parental breeding values were highly consistent between outcross and selfed offspring, indicating that additive effects determine most of the genetic value even in the presence of strong inbreeding depression. We developed a novel linkage scan to identify quantitative trait loci (QTL) representing large-effect rare variants carried by only a single parent, which were more important in teosinte than maize. Teosinte also carried more putative juvenile-acting lethal variants identified by segregation distortion. These results suggest a mixture of mostly polygenic, small-effect partially recessive effects in linkage disequilibrium underlying inbreeding depression, with an additional contribution from rare larger-effect variants that was more important in teosinte but depleted in maize following the domestication bottleneck. Purging associated with the maize domestication bottleneck may have selected against some large effect variants, but polygenic load is harder to purge and overall segregating mutational burden increased in maize compared to teosinte.

Environment-specific selection alters flowering-time plasticity and results in pervasive pleiotropic responses in maize.

Crop genetic diversity for climate adaptations is globally partitioned. We performed experimental evolution in maize to understand the response to selection and how plant germplasm can be moved across geographical zones. Initialized with a common population of tropical origin, artificial selection on flowering time was performed for two generations at eight field sites spanning 25° latitude, a 2800 km transect. We then jointly tested all selection lineages across the original sites of selection, for the target trait and 23 other traits. Modeling intergenerational shifts in a physiological reaction norm revealed separate components for flowering-time plasticity. Generalized and local modes of selection altered the plasticity of each lineage, leading to a latitudinal pattern in the responses to selection that were strongly driven by photoperiod. This transformation led to widespread changes in developmental, architectural, and yield traits, expressed collectively in an environment-dependent manner. Furthermore, selection for flowering time alone alleviated a maladaptive syndrome and improved yields for tropical maize in the temperate zone. Our findings show how phenotypic selection can rapidly shift the flowering phenology and plasticity of maize. They also demonstrate that selecting crops to local conditions can accelerate adaptation to climate change.

Bearded or smooth? Awns improve yield when wheat experiences heat stress during grain fill in the southeastern United States.

The presence or absence of awns-whether wheat heads are 'bearded' or 'smooth' - is the most visible phenotype distinguishing wheat cultivars. Previous studies suggest that awns may improve yields in heat or water-stressed environments, but the exact contribution of awns to yield differences remains unclear. Here we leverage historical phenotypic, genotypic, and climate data for wheat (Triticum aestivum) to estimate the yield effects of awns under different environmental conditions over a 12-year period in the southeastern USA. Lines were classified as awned or awnless based on sequence data, and observed heading dates were used to associate grain fill periods of each line in each environment with climatic data and grain yield. In most environments, awn suppression was associated with higher yields, but awns were associated with better performance in heat-stressed environments more common at southern locations. Wheat breeders in environments where awns are only beneficial in some years may consider selection for awned lines to reduce year-to-year yield variability, and with an eye towards future climates.

Characterization of a Host-Specific Toxic Activity Produced by Bipolaris cookei, Causal Agent of Target Leaf Spot of Sorghum.

Target leaf spot (TLS) of sorghum, caused by the necrotrophic fungus Bipolaris cookei, can cause severe yield loss in many parts of the world. We grew B. cookei in liquid culture and observed that the resulting culture filtrate (CF) was differentially toxic when infiltrated into the leaves of a population of 288 diverse sorghum lines. In this population, we found a significant correlation between high CF sensitivity and susceptibility to TLS. This suggests that the toxin produced in culture may play a role in the pathogenicity of B. cookei in the field. We demonstrated that the toxic activity is light sensitive and, surprisingly, insensitive to pronase, suggesting that it is not proteinaceous. We identified the two sorghum genetic loci most associated with the response to CF in this population. Screening seedlings with B. cookei CF could be a useful approach for prescreening germplasm for TLS resistance.

The genetic architecture of the maize progenitor, teosinte, and how it was altered during maize domestication.

The genetics of domestication has been extensively studied ever since the rediscovery of Mendel's law of inheritance and much has been learned about the genetic control of trait differences between crops and their ancestors. Here, we ask how domestication has altered genetic architecture by comparing the genetic architecture of 18 domestication traits in maize and its ancestor teosinte using matched populations. We observed a strongly reduced number of QTL for domestication traits in maize relative to teosinte, which is consistent with the previously reported depletion of additive variance by selection during domestication. We also observed more dominance in maize than teosinte, likely a consequence of selective removal of additive variants. We observed that large effect QTL have low minor allele frequency (MAF) in both maize and teosinte. Regions of the genome that are strongly differentiated between teosinte and maize (high FST) explain less quantitative variation in maize than teosinte, suggesting that, in these regions, allelic variants were brought to (or near) fixation during domestication. We also observed that genomic regions of high recombination explain a disproportionately large proportion of heritable variance both before and after domestication. Finally, we observed that about 75% of the additive variance in both teosinte and maize is "missing" in the sense that it cannot be ascribed to detectable QTL and only 25% of variance maps to specific QTL. This latter result suggests that morphological evolution during domestication is largely attributable to very large numbers of QTL of very small effect.

Empirical comparison of genomic and phenotypic selection for resistance to Fusarium ear rot and fumonisin contamination in maize.

KEY MESSAGE: GS and PS performed similarly in improving resistance to FER and FUM content. With cheaper and faster genotyping methods, GS has the potential to be more efficient than PS. Fusarium verticillioides is a common maize (Zea mays L.) pathogen that causes Fusarium ear rot (FER) and produces the mycotoxin fumonisin (FUM). This study empirically compared phenotypic selection (PS) and genomic selection (GS) for improving FER and FUM resistance. Three intermating generations of recurrent GS were conducted in the same time frame and from a common base population as two generations of recurrent PS. Lines sampled from each PS and GS cycle were evaluated in three North Carolina environments in 2020. We observed similar cumulative responses to GS and PS, representing decreases of about 50% of mean FER and FUM compared to the base population. The first cycle of GS was more effective than later cycles. PS and GS both achieved about 70% of predicted total gain from selection for FER, but only about 26% of predicted gains for FUM, suggesting that heritability for FUM was overestimated. We observed a 20% decrease in genetic marker variation from PS and 30% decrease from GS. Our greatest challenge was our inability to quickly obtain dense and consistent set of marker genotypes across generations of GS. Practical implementation of GS in individual small-scale breeding programs will require cheaper and faster genotyping methods, and such technological advances will present opportunities to significantly optimize selection and mating schemes for future GS efforts beyond what we were able to achieve in this study.

The genetic architecture of teosinte catalyzed and constrained maize domestication.

The process of evolution under domestication has been studied using phylogenetics, population genetics-genomics, quantitative trait locus (QTL) mapping, gene expression assays, and archaeology. Here, we apply an evolutionary quantitative genetic approach to understand the constraints imposed by the genetic architecture of trait variation in teosinte, the wild ancestor of maize, and the consequences of domestication on genetic architecture. Using modern teosinte and maize landrace populations as proxies for the ancestor and domesticate, respectively, we estimated heritabilities, additive and dominance genetic variances, genetic-by-environment variances, genetic correlations, and genetic covariances for 18 domestication-related traits using realized genomic relationships estimated from genome-wide markers. We found a reduction in heritabilities across most traits, and the reduction is stronger in reproductive traits (size and numbers of grains and ears) than vegetative traits. We observed larger depletion in additive genetic variance than dominance genetic variance. Selection intensities during domestication were weak for all traits, with reproductive traits showing the highest values. For 17 of 18 traits, neutral divergence is rejected, suggesting they were targets of selection during domestication. Yield (total grain weight) per plant is the sole trait that selection does not appear to have improved in maize relative to teosinte. From a multivariate evolution perspective, we identified a strong, nonneutral divergence between teosinte and maize landrace genetic variance-covariance matrices (G-matrices). While the structure of G-matrix in teosinte posed considerable genetic constraint on early domestication, the maize landrace G-matrix indicates that the degree of constraint is more unfavorable for further evolution along the same trajectory.

Characterizing the oligogenic architecture of plant growth phenotypes informs genomic selection approaches in a common wheat population.

BACKGROUND: Genetic variation in growth over the course of the season is a major source of grain yield variation in wheat, and for this reason variants controlling heading date and plant height are among the best-characterized in wheat genetics. While the major variants for these traits have been cloned, the importance of these variants in contributing to genetic variation for plant growth over time is not fully understood. Here we develop a biparental population segregating for major variants for both plant height and flowering time to characterize the genetic architecture of the traits and identify additional novel QTL. RESULTS: We find that additive genetic variation for both traits is almost entirely associated with major and moderate-effect QTL, including four novel heading date QTL and four novel plant height QTL. FT2 and Vrn-A3 are proposed as candidate genes underlying QTL on chromosomes 3A and 7A, while Rht8 is mapped to chromosome 2D. These mapped QTL also underlie genetic variation in a longitudinal analysis of plant growth over time. The oligogenic architecture of these traits is further demonstrated by the superior trait prediction accuracy of QTL-based prediction models compared to polygenic genomic selection models. CONCLUSIONS: In a population constructed from two modern wheat cultivars adapted to the southeast U.S., almost all additive genetic variation in plant growth traits is associated with known major variants or novel moderate-effect QTL. Major transgressive segregation was observed in this population despite the similar plant height and heading date characters of the parental lines. This segregation is being driven primarily by a small number of mapped QTL, instead of by many small-effect, undetected QTL. As most breeding populations in the southeast U.S. segregate for known QTL for these traits, genetic variation in plant height and heading date in these populations likely emerges from similar combinations of major and moderate effect QTL. We can make more accurate and cost-effective prediction models by targeted genotyping of key SNPs.

Exploring the knowledge and attitudes of women of reproductive age from the general public towards egg donation and egg sharing: a UK-based study.

STUDY QUESTION: What are the knowledge and views of UK-based women towards egg donation (ED) and egg sharing (ES)? SUMMARY ANSWER: Lacking knowledge of the practices of ED and ES could be an influential factor in donor egg shortages, rather than negative perceptions or lack of donor anonymity and financial incentives. WHAT IS KNOWN ALREADY: The increasing age of women trying to conceive has led to donor egg shortages, with ED and ES failing to meet demand. Indeed, in recent years in the UK, ES numbers have fallen. This results in long waiting lists, forcing patients abroad for fertility treatment to take up cross border reproductive care. Previous research suggests a lack of knowledge of ED among members of the general public; however, no study has yet assessed knowledge or views of ES in the general public. STUDY DESIGN, SIZE, DURATION: Six hundred and thirty-five UK-based women over 18 years were voluntarily recruited from social media community groups by convenience sampling. The recruitment period was from February to April 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants completed a previously validated questionnaire regarding female fertility, ED and ES, including knowledge, perceptions and approval of the practices and relevant legislation. This included ranking key benefits and issues regarding egg sharing. The questionnaire was completed using the online Qualtrics survey software. Statistical analysis was conducted using SPSS. MAIN RESULTS AND THE ROLE OF CHANCE: Regarding knowledge of ED and ES, 56.3% and 79.8%, respectively had little or no prior knowledge. Upon explanation, most approved of ED (85.8%) and ES (70.4%). A greater proportion of respondents would donate to a family member/friend (49.75%) than to an anonymous recipient (35.80%). Overall, ES was viewed less favourably than ED, with ethical and practical concerns highlighted. Women aged 18-30 years were significantly more likely to approve of egg donation practice compared to those aged >30 years (P < 0.0001). Those against ES found fears of financial coercion or negative psychological wellbeing the most concerning. About 35.8% and 49.7% would personally consider anonymous and known ED, respectively, whilst 56.7% would consider ES. Those answering in favour of egg sharing were significantly more likely to give higher benefit ratings compared to those against the practice (P < 0.001). Most agreed (55.8%) with and were not deterred to donate (60.1%) by the 'Disclosure of Donor Identity' legislation. Only 31.6% agreed with the compensatory cap; however, 52.7% would not be more motivated to donate by an increased cap. LIMITATIONS, REASONS FOR CAUTION: There were several limitations of the study, including the use of convenience sampling and the voluntary nature of participation opening the study up to sampling and participation bias. Finally, closed questions were predominantly used to allow the generation of quantitative data and statistical analysis. However, this approach prevented opinion justification and qualitative analysis, limiting the depth of conclusions drawn. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study to survey the general public's knowledge and views of ED/ES using a previously validated questionnaire. The conclusion that lack of knowledge could be contributing to the current donor shortfall in the UK demonstrates that campaigns to inform women of the practices are necessary to alleviate donor oocyte shortages. STUDY FUNDING/COMPETING INTEREST(S): No external funds were used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

Heterosis of leaf and rhizosphere microbiomes in field-grown maize.

Macroorganisms' genotypes shape their phenotypes, which in turn shape the habitat available to potential microbial symbionts. This influence of host genotype on microbiome composition has been demonstrated in many systems; however, most previous studies have either compared unrelated genotypes or delved into molecular mechanisms. As a result, it is currently unclear whether the heritability of host-associated microbiomes follows similar patterns to the heritability of other complex traits. We take a new approach to this question by comparing the microbiomes of diverse maize inbred lines and their F1 hybrid offspring, which we quantified in both rhizosphere and leaves of field-grown plants using 16S-v4 and ITS1 amplicon sequencing. We show that inbred lines and hybrids differ consistently in the composition of bacterial and fungal rhizosphere communities, as well as leaf-associated fungal communities. A wide range of microbiome features display heterosis within individual crosses, consistent with patterns for nonmicrobial maize phenotypes. For leaf microbiomes, these results were supported by the observation that broad-sense heritability in hybrids was substantially higher than narrow-sense heritability. Our results support our hypothesis that at least some heterotic host traits affect microbiome composition in maize.

A single-centre review of iatrogenic anaemia in adult intensive care.

OBJECTIVES: (a) To quantify the volume of diagnostic blood loss (DBL) and evaluate its impact on intensive care unit (ICU) patients, (b) examine the correlation between severity of disease and DBL and (c) identify potentially vulnerable patient subgroups. BACKGROUND: Iatrogenic anaemia is an important problem amongst ICU patients, with significant daily DBL. METHODS: A single-centre observational cohort study was conducted at St George's Hospital, London, cardiac and general ICU. Forty patients were included in the study. Variables measured were volume of blood collected and discarded on a daily basis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, frequency of phlebotomy, haemoglobin concentration before and after admission to ICU, reason for admission and complications developed in ICU. RESULTS: Mean (SD) total volume drawn per patient per day over 4 days was 86.3 mL (19.58). Nearly 30% of the total blood taken was discarded. There was a strong positive correlation between patients admitted because of sepsis and volume of DBL (P < .01), APACHE II score and volume taken (P = .01), patients who developed respiratory failure requiring ventilation and volume taken (P < .01) and patients who had received a blood transfusion and volume taken (P < .01). Haemoglobin concentration on discharge was negatively associated with DBL volume (P < .01). CONCLUSION: High volumes of blood were taken and discarded from the study population, possibly reflecting the fact that there are no guidelines for ICU staff in terms of the amount of blood that needs to be withdrawn in order to "prime" access lines.

Modifications to a LATE MERISTEM IDENTITY1 gene are responsible for the major leaf shapes of Upland cotton (Gossypium hirsutum L.).

Leaf shape varies spectacularly among plants. Leaves are the primary source of photoassimilate in crop plants, and understanding the genetic basis of variation in leaf morphology is critical to improving agricultural productivity. Leaf shape played a unique role in cotton improvement, as breeders have selected for entire and lobed leaf morphs resulting from a single locus, okra (l-D1), which is responsible for the major leaf shapes in cotton. The l-D1 locus is not only of agricultural importance in cotton, but through pioneering chimeric and morphometric studies, it has contributed to fundamental knowledge about leaf development. Here we show that an HD-Zip transcription factor homologous to the LATE MERISTEM IDENTITY1 (LMI1) gene of Arabidopsis is the causal gene underlying the l-D1 locus. The classical okra leaf shape allele has a 133-bp tandem duplication in the promoter, correlated with elevated expression, whereas an 8-bp deletion in the third exon of the presumed wild-type normal allele causes a frame-shifted and truncated coding sequence. Our results indicate that subokra is the ancestral leaf shape of tetraploid cotton that gave rise to the okra allele and that normal is a derived mutant allele that came to predominate and define the leaf shape of cultivated cotton. Virus-induced gene silencing (VIGS) of the LMI1-like gene in an okra variety was sufficient to induce normal leaf formation. The developmental changes in leaves conferred by this gene are associated with a photosynthetic transcriptomic signature, substantiating its use by breeders to produce a superior cotton ideotype.

Training population selection and use of fixed effects to optimize genomic predictions in a historical USA winter wheat panel.

KEY MESSAGE: The optimization of training populations and the use of diagnostic markers as fixed effects increase the predictive ability of genomic prediction models in a cooperative wheat breeding panel. Plant breeding programs often have access to a large amount of historical data that is highly unbalanced, particularly across years. This study examined approaches to utilize these data sets as training populations to integrate genomic selection into existing pipelines. We used cross-validation to evaluate predictive ability in an unbalanced data set of 467 winter wheat (Triticum aestivum L.) genotypes evaluated in the Gulf Atlantic Wheat Nursery from 2008 to 2016. We evaluated the impact of different training population sizes and training population selection methods (Random, Clustering, PEVmean and PEVmean1) on predictive ability. We also evaluated inclusion of markers associated with major genes as fixed effects in prediction models for heading date, plant height, and resistance to powdery mildew (caused by Blumeria graminis f. sp. tritici). Increases in predictive ability as the size of the training population increased were more evident for Random and Clustering training population selection methods than for PEVmean and PEVmean1. The selection methods based on minimization of the prediction error variance (PEV) outperformed the Random and Clustering methods across all the population sizes. Major genes added as fixed effects always improved model predictive ability, with the greatest gains coming from combinations of multiple genes. Maximum predictabilities among all prediction methods were 0.64 for grain yield, 0.56 for test weight, 0.71 for heading date, 0.73 for plant height, and 0.60 for powdery mildew resistance. Our results demonstrate the utility of combining unbalanced phenotypic records with genome-wide SNP marker data for predicting the performance of untested genotypes.

Intracranial volume (ICV) in isolated sagittal craniosynostosis: a retrospective case-matched-control study.

PURPOSE: Children with sagittal craniosynostosis (SC) are at risk of developing raised intracranial pressure (ICP). This is thought to result from cephalocranial disproportion-the restriction of normal cerebral development by a small cranial vault. It remains unclear whether intracranial volume (ICV) is altered in SC. This study offers a novel volumetric analysis of the scaphocephalic skull, comparing supratentorial (ST) volume, infratentorial (IT) volume, and total ICV of patients with sagittal synostosis to normal controls. METHODS: ICVs of 32 consecutive patients undergoing total calvarial vault remodelling (TCVR) for isolated SC were compared to 32 age- and sex-matched normal controls. ICV was measured with manual techniques on head computerised tomographic (CT) scans using OsiriX software. A paired t test was used to compare data between cases and controls. RESULTS: Mean total ICV, ST volume and IT volume were larger in SC than in controls, except in females > 6 months of age. There was no statistical significance. Regression analysis demonstrated larger ICVs in diseased children than in controls younger than 10 months, at which age trend lines intersected and the reverse became true for older children. This likely represents an evolving risk of cephalocranial disproportion beyond 10 months of age. The IT/ST volume ratio was conserved in scaphocephaly, and very closely approximated that of controls. CONCLUSIONS: Sagittal craniosynostosis appears to be associated with a larger cranial vault at less than 10 months and a smaller vault at greater than 10 months, although statistical significance was not achieved.

An Overview and Predictors of Achieving the Postoperative Ceiling Effect of the WOMAC Score Following Total Knee Arthroplasty.

BACKGROUND: To describe the ceiling effect for the components of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and identify preoperative independent predictors for patients who achieve maximal scores (ceiling effect) after total knee arthroplasty (TKA). METHODS: A retrospective cohort of 2589 patients undergoing a primary TKA were identified from an established arthroplasty database. Patient demographics, WOMAC and Short Form 12 (SF-12) scores were collected preoperatively and 1 year postoperatively. Logistic regression analysis was used to identify independent preoperative predictors of patients achieving ceiling scores. RESULTS: The ceiling effect was 26.8% (n = 695) for the pain score, 6.4% (n = 165) for the function score, and 21.2% (n = 548) for the stiffness score. Lower body mass index (P = .001), absence of gastric ulceration (P = .04), absence of anemia (P = .02), absence of depression (P = .004), and absence of back pain (P < .001) and better preoperative WOMAC pain and SF-12 physical (P = .01) and mental (P < .001) scores were associated with a ceiling WOMAC pain score. Male gender (P = .03), lower body mass index (P = .040), absence of gastric ulceration (P = .004), and absence of back pain (P < .001) and better preoperative SF-12 physical (P = .02) scores were associated with a ceiling WOMAC function score. Male gender (P = .001), absence of back pain (P < .001), and better preoperative WOMAC stiffness score (P = .005) and SF-12 mental (P = .001) scores were associated with a ceiling WOMAC stiffness score. CONCLUSION: The WOMAC pain and stiffness components demonstrated a high ceiling effect but in contrast the functional score had a low ceiling effect. The absence of back pain was a common predictive factor for all 3 components and had the greatest impact upon the likelihood of achieving a ceiling score.

Asynchronous Bilateral Total Knee Arthroplasty: Predictors of the Functional Outcome and Patient Satisfaction for the Second Knee Replacement.

BACKGROUND: The primary aim of this study is to identify independent preoperative predictors of outcome and patient satisfaction for the second total knee arthroplasty (TKA). METHODS: A retrospective cohort of 454 patients undergoing an asynchronous (6 weeks or more apart) bilateral primary TKA were identified from an arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form-12 scores were collected preoperatively and 1 year postoperatively. Overall patient satisfaction was assessed at 1 year. RESULTS: The 1 year WOMAC pain score (P = .01), and improvement in WOMAC pain (P < .001) and functional (P = .002) scores were significantly lower for the second TKA. Worse preoperative WOMAC pain, function, and stiffness scores were demonstrated to be independent predictors of improvement in the WOMAC pain, function, and stiffness scores, respectively, for both the first and second TKA. The overall rate of satisfaction with the first TKA was 94.0% and 94.7% for the second TKA (P = .67). The rate of satisfaction for the second TKA was 77.8% for patients that were dissatisfied with their first TKA, which was an independent predictor of dissatisfaction (P = .02). CONCLUSION: Improvement in pain and function is less with the second TKA, but the satisfaction rate remains similar. There are common independent predictors for change in the WOMAC score for the first and second TKA; however, the predictors of satisfaction were different with no common factors. Patients that were dissatisfied with their first TKA were more likely to be dissatisfied with their second TKA. LEVEL OF EVIDENCE II: Prognostic retrospective cohort study.

Intraarticular injection of a Tin-117 m radiosynoviorthesis agent in normal canine elbows causes no adverse effects.

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin-117 m (117m Sn) colloid after intra-articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine-18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5-1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra-articular injection of 117m Sn colloid (92.5 MBq; 1-1.5 ml). Post-injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45-47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the 117m Sn activity was retained in the joint for 45-47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the 117m Sn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.