Computer-vision analysis of craniofacial dysmorphology in 22q11.2 deletion syndrome and psychosis spectrum disorders.

BACKGROUND: Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders. METHODS: Here, 2D digital photographs were collected from 22q11DS (n = 150), PS (n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics-a semi-automated machine learning technique that localizes and measures facial features. RESULTS: F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements. CONCLUSIONS: The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.

Feasibility of a virtual reality course on adult tracheostomy safety skills.

The National Tracheostomy Safety Project has run high-quality, face-to-face skills courses since 2009. The aim of this project was to produce a virtual reality version of the established course and evaluate its impact on participant learning, and participant and faculty satisfaction. Healthcare staff and students were recruited and randomised to attend one of (1) a face-to-face traditional course (control); (2) a virtual reality course at a conference centre with on-site technical support; (3) a fully remote virtual reality course; the virtual reality groups were combined for the analysis of learning outcomes and satisfaction. The primary outcome was the difference in pre/post-course knowledge scores on a 30-item questionnaire; secondary outcomes included knowledge retention, usability, comfort/side effects and participant performance in a simulated tracheostomy emergency. Thirty-seven participants and 15 faculty participated in this study. There was no significant difference between mean pre/post-course scores from the face-to-face (from 21.1 to 23.1; +2) and combined virtual reality (from 17.1 to 21.1; +4) groups, with both showing improvement (p = 0.21). The mean System Usability Scale score for virtual reality was 76.8 (SD 12.6), which is above average; the median Simulator Sickness Questionnaire score was 7.5 (IQR 3.7-22.4), indicating minimal symptoms. All participants resolved the primary clinical problem in the simulated emergency, but the virtual reality (VR) group was slower overall (mean difference 61.8 s, p = 0.003). This technical feasibility study demonstrated that there was no difference in participant knowledge immediately after and 4 weeks following face-to-face and virtual reality courses. Virtual reality offers an immersive experience that can be delivered remotely and offers potential benefits of reducing travel and venue costs for attendees, therefore increasing the flexibility of training opportunities.

Real-World Performance Benchmarks in the Reading Ability of Prescription Drug Labels by Community-Dwelling Older Adults.

BACKGROUND: Despite known recommendations regarding standards for print size and the intuitive importance of vision in reading prescription labels, the predictive nature of vision and prescription label readability remains largely undefined. Furthermore, while the importance of vision is recognized, various demographic factors associated with the ability to read prescription labels have not been fully elucidated. OBJECTIVE: Describe relationships between visual acuity, point size, and readability of prescription labels and provide insight into demographic factors associated with prescription label readability. METHODS: Cross-sectional examination of prescription label readability by older, community-dwelling adults. Subjects were evaluated as to demographics, visual acuity, and ability to read test instruments consisting of unaltered prescription label features of five medications dispensed by community pharmacies and two drug samples. Descriptive statistics in conjunction with a logit predictive model were employed for data analysis. RESULTS: Instructions for medication use were most recognizable, identified and correctly read by 95.60% of the study cohort while directions for the use of drug samples were lowest (34.91%). Among prescription label features, auxiliary labels consistently demonstrated poor readability. Level of visual acuity was statistically related to the ability to read prescription labels while identifying prescription label components increased proportionally with point size. Race, gender, and history of a recent eye examination were statistically significant predictors of prescription label reading ability. Visual acuity alone was found to explain approximately 26% of the variablity in ability to read Rx labels. CONCLUSION: Visual acuity is predictive of the ability to access Rx label information and should be considered a modifiable variable for improving prescription label reading ability amenable by appropriate eye care and spectacle correction.

Error codes at autopsy to study potential biases in diagnostic error.

OBJECTIVES: Current autopsy practice guidelines do not provide a mechanism to identify potential causes of diagnostic error (DE). We used our autopsy data registry to ask if gender or race were related to the frequency of diagnostic error found at autopsy. METHODS: Our autopsy reports include International Classification of Diseases (ICD) 9 or ICD 10 diagnostic codes for major diagnoses as well as codes that identify types of error. From 2012 to mid-2015 only 2 codes were used: UNDOC (major undocumented diagnoses) and UNCON (major unconfirmed diagnoses). Major diagnoses contributed to death or would have been treated if known. Since mid-2015, codes included specific diagnoses, i.e. undiagnosed or unconfirmed myocardial infarction, infection, pulmonary thromboembolism, malignancy, or other diagnosis as well as cause of death. Adult autopsy cases from 2012 to 2019 were assessed for DE associated with reported sex or race (nonwhite or white). 528 cases were evaluated between 2012 and 2015 and 699 between 2015 and 2019. RESULTS: Major DEs were identified at autopsy in 65.9 % of cases from 2012 to 2015 and in 72.1 % from 2015 to 2019. From 2012 to 2015, female autopsy cases showed a greater frequency in 4 parameters of DE, i.e., in the total number of cases with any error (p=0.0001), in the number of cases with UNDOC errors (p=0.0038) or UNCON errors (p=0.0006), and in the relative proportions of total numbers of errors (p=0.0001). From 2015 to 2019 undocumented malignancy was greater among males (p=0.0065); no other sex-related error was identified. In the same period some DE parameters were greater among nonwhite than among white subjects, including unconfirmed cause of death (p=0.035), and proportion of total error diagnoses (p=0.0003), UNCON diagnoses (p=0.0093), and UNDOC diagnoses (p=0.035). CONCLUSIONS: Coding for DE at autopsy can identify potential effects of biases on diagnostic error.

In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Effect of Age and Viscosity on Duration of Corneal Anesthesia with Topical 2% Lidocaine Administration.

Purpose: Formulation viscosity and patient-specific parameters such as age are important considerations in achieving patient comfort for prolonged anterior segment surgical procedures. In this study, we report pharmacodynamic and pharmacokinetic parameters of topical 2% lidocaine anesthetic decay based on formulation viscosity and subject age. Methods: Extemporaneous 2% lidocaine solution was compounded with varying percentages of carboxymethylcellulose (CMC) to adjust product viscosity. Juvenile and adult New Zealand White rabbits were utilized as a model for lidocaine-induced corneal anesthesia analysis. Following application of 20 µL in 1 eye of each animal, corneal sensitivity was measured using a Cochet-Bonnet esthesiometer at baseline and at 1-min intervals until recovery to baseline. Subsequent to washout period, the experiment was repeated for 3 replicate experiments. Results: A one-phase exponential decay model was utilized to describe rate of anesthesia decay. Bioavailability increased in a manner disproportionate to both tear film concentration and solution viscosity. In adult animals, half-life of anesthetic decay was found to range from 6.03 min with 2% lidocaine in 0.5% CMC to 9.45 min with 2% lidocaine in 1.5% CMC. In juveniles, half-life was found to be 4.46 and 3.58 min for 2% lidocaine in 1.5% CMC and commercial 2% lidocaine gel, respectively. Conclusions: Decay parameters of lidocaine-induced corneal anesthesia appear disparate from viscosity. It is postulated that viscosity-related increase in corneal contact time through reduced drainage plays a critical role in increasing bioavailability of topical anesthetics in our experimental findings, although nonlinear in character. Age is found to be an important mediator of lidocaine-induced corneal anesthesia.

Contralateral interhemispheric transfalcine approach to precuneal glioblastoma: fluorescein guided microsurgical resection and endoscopic microinspection tool.

Maximum safe resection remains a primary goal in the treatment of glioblastoma, with gross-total resection conveying additional survival benefit. Multiple intraoperative visualization techniques have been developed to improve the extent of resection. Herein, the authors describe the use of fluorescein and endoscopic assistance with a novel microinspection device in achieving a gross-total resection of a deep seated precuneal glioblastoma. An interhemispheric transfalcine approach was utilized and microsurgical resection was completed with fluorescein guidance. A 45° endoscope was then used to inspect the resection bed, and remaining areas of concern were then resected under endoscopic visualization. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21195.

Semantic processing features and schizotypal traits: A test-retest study.

Semantic processing abnormalities have been observed across the schizophrenia spectrum. However, it is unclear whether associations between semantic processing measures and schizotypal traits are stable over time. The current study aimed to explore the temporal stability of semantic processing measures and their correlations with schizotypal traits. In this study, we used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits and explored the association between schizotypal traits and semantic processing measures (i.e., N400- a large negativity with a broad scalp distribution, peaking around 400 ms after the presentation of any potentially meaningful stimulus) at baseline (Time 1; n = 63) and 3 months later (Time 2; n = 44). Repeated-measure ANOVA was conducted to examine the stability of the semantic processing measures; the intraclass correlation coefficient (ICC) was used to examine test-retest reliability; Pearson's r was calculated to explore associations between schizotypal traits and semantic processing measures. Results showed that both behavioral (reaction times) and N400 measures showed high reliability but low temporal stability. N400 latency for semantically unrelated stimuli was correlated with the cognitive-perceptual and the disorganized dimensions of schizotypal traits at Time 2. In conclusion, semantic processing measures generally showed good reliability. Schizotypal traits were correlated with N400 latencies in the current sample, but further studies are needed to examine whether this association is stable.

Hierarchical data visualization of experimental erythrocyte aggregation employing cross correlation and optical flow applications.

Appraisal of microvascular erythrocyte velocity as well as aggregation are critical features of hemorheological assessment. Examination of erythrocyte velocity-aggregate characteristics is critical in assessing disorders associated with coagulopathy. Microvascular erythrocyte velocity can be assessed using various methodologic approaches; however, the shared assessment of erythrocyte velocity and aggregation has not been well described. The purpose of this study therefore is to examine three independent erythrocyte assessment strategies with and without experimentally induced aggregation in order to elucidate appropriate analytic strategy for combined velocity/aggregation assessment applicable to in-vivo capillaroscopy. We employed a hierarchical microfluidic model combined with Bland-Altman analysis to examine agreement between three methodologies to assess erythrocyte velocity appropriate for interpretation of cinematography of in-vivo microvascular hemorheology. We utilized optical and manual techniques as well as a technique which we term transversal temporal cross-correlation (TTC) to observe and measure both erythrocyte velocity and aggregation. In general, optical, manual and TTC agree in estimation of velocity at relatively low flow rate, however with an increase in infusion rate the optical flow method yielded the velocity estimates that were lower than the TTC and manual velocity estimates. We suggest that this difference was due to the fact that slower moving particles close to the channel wall were better illuminated than faster particles deeper in the channel which affected the optical flow analysis. Combined velocity/aggregation appraisal using TTC provides an efficient approach for estimating erythrocyte aggregation appropriate for in-vivo applications. We demonstrated that the optical flow and TTC analyses can be used to estimate erythrocyte velocity and aggregation both in ex-vivo microfluidics laboratory experiments as well as in-vivo recordings. The simplicity of TTC method may be advantageous for developing velocity estimate methods to be used in the clinic. The trade-off is that TTC estimation cannot capture features of the flow based on optical flow analysis of individually tracked particles.

Female astronauts: Impact of space radiation on menopause.

Space travel has different effects on the reproductive capacity of women compared to men. The radiation exposure intrinsic to deep space travel causes destruction of some of a woman's primordial follicles. Data suggests that a typical Mars mission may reduce a women's ovarian reserve by about 50%. This has consequences to a woman's reproductive capacity and, more significantly, decreases the time interval to her menopause. A reduced time interval to menopause is associated with earlier mortality. Estrogen replacement therapy and cryopreservation of a female astronaut's oocytes may be used to address these issues. However, cortical tissue freezing provides advantages to more directly compensate for these workplace complications. Cortical tissue freezing especially provides advantages if there are plans to reproduce in an extraterrestrial location.

Berry Anthocyanin, Acid, and Volatile Trait Analyses in a Grapevine-Interspecific F2 Population Using an Integrated GBS and rhAmpSeq Genetic Map.

Increased map density and transferability of markers are essential for the genetic analysis of fruit quality and stress tolerance in interspecific grapevine populations. We used 1449 GBS and 2000 rhAmpSeq markers to develop a dense map for an interspecific F2 population (VRS-F2) that was derived by selfing a single F1 from a Vitis riparia x 'Seyval blanc' cross. The resultant map contained 2519 markers spanning 1131.3 cM and was highly collinear with the Vitis vinifera 'PN40024' genome. Quantitative trait loci (QTL) for berry skin color and flower type were used to validate the map. Four rhAmpSeq transferable markers were identified that can be used in pairs (one pistillate and one hermaphroditic) to predict pistillate and hermaphrodite flower type with ≥99.7% accuracy. Total and individual anthocyanin diglucoside QTL mapped to chromosome 9 near a 5-O-GLUCOSYLTRANSFERASE candidate gene. Malic acid QTL were observed on chromosome 1 and 6 with two MALATE DEHYRDROGENASE CYTOPLASMIC 1 and ALUMINUM-ACTIVATED MALATE TRANSPORTER 2-LIKE (ALMT) candidate genes, respectively. Modeling malic acid identified a potential QTL on chromosome 8 with peak position in proximity of another ALMT. A first-ever reported QTL for the grassy smelling volatile (E)-2-hexenal was found on chromosome 2 with a PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE candidate gene near peak markers.

Small Molecule Inhibitors of Nuclear Export and the Amelioration of Lupus by Modulation of Plasma Cell Generation and Survival.

OBJECTIVE: To investigate the hypothesis that selective inhibitors of nuclear export (SINE compounds), recently approved for treatment of refractory plasma cell (PC) malignancy, may have potential in the treatment of lupus. METHODS: Female NZB/NZW mice were treated with the SINE compound KPT-350 or vehicle control. Tissue specimens were harvested and analyzed by flow cytometry, using standard markers. Nephritis was monitored by determining the proteinuria score and by histologic analysis of kidney specimens. Serum anti-double-stranded DNA (anti-dsDNA) levels were measured by enzyme-linked immunosorbent assay, and total numbers of IgG-secreting and dsDNA-specific antibody-secreting cells were assessed by enzyme-linked immunospot assay. RESULTS: KPT-350 abrogated murine lupus nephritis at both early and late stages of the disease and rapidly impaired generation of autoreactive PCs in germinal centers (GCs). SINE compounds inhibited the production of NF-κB-driven homeostatic chemokines by stromal cells, altering splenic B and T cell strategic positioning and significantly reducing follicular helper T cell, GC B cell, and autoreactive PC counts. KPT-350 also decreased levels of cytokines and chemokines involved in PC survival and recruitment in the kidney of lupus-prone mice. Exportin 1, the target of SINE compounds, was detected in GCs of human tonsils, splenic B cells of lupus patients, and multiple B cell subsets in the kidneys of patients with lupus nephritis. CONCLUSION: Collectively, our results provide support for the therapeutic potential of SINE compounds, via their targeting of several molecular and cellular pathways critical in lupus pathogenesis, including autoantibody production by plasma cells.

A meta-analysis of variability in conjunctival microvascular hemorheology metrics.

Conjunctival hemorheology has been used analytically to assess qualities of blood flow associated with various forms of cardiovascular disorders including diabetes mellitus, stroke, and sickle cell disease. Although conjunctival axial red blood cell velocity (Vax) has been demonstrated in varying disease states, benchmark measures of Vax are not well-defined. Due to various methodologic differences in assessment of Vax, interstudy consistency of hemorheological metrics is susceptible to both systematic and random error. Our study examines interstudy heterogeneity of Vax as measured in the conjunctival microvasculature of healthy subjects and assesses the overall perturbation of Vax based on disease state. Furthermore, our study aims to establish a potential range of normative Vax by comparing inter-study measurements in healthy patients. The most widely employed analytic approach to assess Vax was space-time analysis (n = 30). Using a meta-analytic approach, the prediction interval for Vax in healthy subjects among 20 studies ranged from 0.32-2.60 mm/s with a combined effect size of 0.52 ± 0.03 (CI: 0.46-0.59) mm/s. Inter-study comparison of Vax in healthy patients showed a high degree of variability (I2: 98.96%), due to studies with low measurement precision and/or dissimilar analytic methodology. Neither age nor diameter was a clinically significant moderator of Vax measurements in healthy patients. The combined effect size, defined as the composite Hedge's g of studies comparing healthy and disease state mean Vax, was 0.21 ± 0.13. High heterogeneity (I2: 80.48%) was observed in studies analyzing the difference between mean Vax in healthy and disease state patients. This heterogeneity was also observed when the difference in mean Vax between healthy and disease state patients was assessed in subgroups based on disease condition (I2: vascular disease 33%, sickle cell disease 62.22%, other 83.43%). Age was found to be a significant moderator (p = 0.048, ß = -0.40) of Hedge's g while diameter was not. No significant publication bias was observed in studies presenting healthy patient Vax or in studies comparing Vax between healthy and disease state patients. In summary, although homogeneity can be seen in healthy group Vax measurements, a high degree of statistical heterogeneity is found in Vax assessment comparing healthy and disease conditions that is not fully explained by methodologic variability.

Variable abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson's disease (PD) and parkinsonism features.

OBJECTIVES: Ascertain and quantify abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson's disease (PD) and parkinsonism features based on a statistical predictive modeling strategy for PLR classification. METHODS: Exploratory cohort analysis of pupillary kinetics in non-disease controls, PD subjects, and subjects with parkinsonism features using chromatic pupillometry. Receiver operating characteristic (ROC) curve interpretation of pupillary changes consistent with abnormality of intrinsically photosensitive retinal ganglion cells (ipRGCs) was employed using a thresholding algorithm to discriminate pupillary abnormality between study groups. RESULTS: Twenty-eight subjects were enrolled, including 17 PD subjects (age range 64-85, mean 70.65) and nine controls (age range 48-95, mean 63.89). Two subjects were described as demonstrating parkinsonism symptoms due to presumed Lewy body dementia and motor system atrophy (MSA) respectively. On aggregate analysis, PD subjects demonstrated abnormal but variable pupillary dynamics suggestive of ipRGC abnormality. Subjects with parkinsonism features did not demonstrate pupillary changes consistent with ipRGC abnormality. There was no relationship between levodopa equivalent dosage or PD severity and ipRGC abnormality. The pupillary test sensitivity in predicting PD was 0.75 and likelihood ratio was 1.2. CONCLUSIONS: ipRGC deficit is demonstrated in PD subjects; however, the degree and constancy of abnormality appear variable.

Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.

Negative symptoms and cognitive deficits contribute strongly to disability in schizophrenia, and are resistant to existing medications. Recent drug development has targeted enhanced NMDA function by increasing mGluR2/3 signaling. However, the clinical utility of such agents remains uncertain, and markers of brain circuit function are critical for clarifying mechanisms and understanding individual differences in efficacy. We conducted a double-blind, placebo-controlled, randomized cross-over (14 day washout) pilot study evaluating adjunctive use of the mGluR2 positive allosteric modulator AZD8529 (80 mg daily for 3 days), in chronic stable patients with schizophrenia (n = 26 analyzed). We focused on 3 T fMRI response in frontostriatal regions during an n-back working memory task, testing the hypothesis that AZD8529 produces fMRI changes that correlate with improvement in negative symptoms and cognition. We found that AZD8529 did not produce significant group-average effects on symptoms or cognitive accuracy. However, AZD8529 did increase n-back fMRI activation in striatum (p < 0.0001) and anterior cingulate/paracingulate (p = 0.002). Greater drug-versus-placebo effects on caudate activation significantly correlated with greater reductions in PANSS negative symptom scores (r = -0.42, p = 0.031), and exploratory correlations suggested broader effects across multiple symptom domains and regions of interest. These findings demonstrate that fMRI responses to mGluR2 positive modulation relate to individual differences in symptom reduction, and could be pursued for future biomarker development. Negative clinical results at the group level should not lead to premature termination of investigation of this mechanism, which may benefit an important subset of individuals with schizophrenia. Imaging biomarkers may reveal therapeutic mechanisms, and help guide treatment toward specific populations.

The spectrum of macrophage-predominant inflammatory myocardial disease presenting as fulminant heart failure.

BACKGROUND: Endomyocardial biopsy results are integral for diagnosis and management of myocarditis. Current diagnostic classifications of myocarditis are based on the microscopic and immunochemical characterization of inflammation do not include monocyte/macrophage-predominant (i.e. "histiocytic") myocarditis as a histologic subtype. METHODS: Endomyocardial biopsies from 6 patients with sudden heart failure were reviewed by 3 cardiac pathologists. Routine stains and immunostains to identify T cells and monocytes/macrophages, complement C4d, and endothelium were applied. Electron microscopy was performed in 2 cases. RESULTS: The 6 patients included 2 with diagnoses of systemic lupus erythematosus (SLE) and 4 without known disease. Microscopy showed space-occupying inflammation in 2 cases and interstitial inflammation in 4. No giant cell myocarditis or eosinophilic myocarditis was found. Immunostains showed infiltration predominantly by macrophages and/or monocytes with markedly fewer T cells. In 4 of 6 cases necrotic cells were immunopositive for complement C4d. Monocytes we identified immunochemically within the microvasculature in 5 cases and by electron microscopy in 2. Patients with SLE had microvascular C4d positivity or interstitial/sarcolemmal staining. Clinical outcomes ranged from spontaneous resolution to persistent heart failure requiring an internal cardioverter/defibrillator. CONCLUSIONS: (1) Heart failure with CD68 predominant inflammation ("histiocytic" myocardial inflammatory disease, HMID) occurs with variable clinical presentation and outcome; (2) HMID may be primary or secondary; (3) some cases of HMID show features suggestive of antibody and/or complement mediated myocardial injury, and (4) HMID is a diagnosis distinct from those in classification systems currently in use.

The Genetic Basis of Anthocyanin Acylation in North American Grapes (Vitis spp.).

Hydroxycinnamylated anthocyanins (or simply 'acylated anthocyanins') increase color stability in grape products, such as wine. Several genes that are relevant for anthocyanin acylation in grapes have been previously described; however, control of the degree of acylation in grapes is complicated by the lack of genetic markers quantitatively associated with this trait. To characterize the genetic basis of anthocyanin acylation in grapevine, we analyzed the acylation ratio in two closely related biparental families, Vitis rupestris B38 × 'Horizon' and 'Horizon' × Illinois 547-1, for 2 and 3 years, respectively. The acylation ratio followed a bimodal and skewed distribution in both families, with repeatability estimates larger than 0.84. Quantitative trait locus (QTL) mapping with amplicon-based markers (rhAmpSeq) identified a strong QTL from 'Horizon' on chromosome 3, near 15.85 Mb in both families and across years, explaining up to 85.2% of the phenotypic variance. Multiple candidate genes were identified in the 14.85-17.95 Mb interval, in particular, three copies of a gene encoding an acetyl-CoA-benzylalcohol acetyltransferase-like protein within the two most strongly associated markers. Additional population-specific QTLs were found in chromosomes 9, 10, 15, and 16; however, no candidate genes were described. The rhAmpSeq markers reported here, which were previously shown to be highly transferable among the Vitis genus, could be immediately implemented in current grapevine breeding efforts to control the degree of anthocyanin acylation and improve the quality of grapes and their products.

Study of ultrasound thrombolysis using acoustic bubbles in a microfluidic device.

Thrombosis is a common medical entity associated with many forms of cardiovascular disease including myocardial infarction and stroke. Recently, ultrasound thrombolysis has emerged as a promising technique for thrombosis treatment by delivering acoustic waves onto blood clots. In this study, an ultrasound thrombolysis method is presented using an acoustic bubble-based microfluidic device. With acoustic actuation, microstreaming flow is created in the microchannel by oscillating bubbles, breaking up the blood clots in blood samples in a few milliseconds. In a low-frequency field, the effects of bubble size on microstreaming patterns and thrombolysis have been experimentally studied. Using image processing techniques, we have quantitatively investigated the relationship between the input signal and the thrombolysis performance. Additionally, the viability test proved that there are no significant detrimental effects on the blood cells after acoustic actuation. This acoustic bubble-based microfluidic device is demonstrated to be a promising platform for quantitative analysis of ultrasound thrombolysis. It opens up possibilities for future development of ultrasound thrombolysis devices for the diagnosis and treatment of heart diseases.