Trichomonas vaginalis extracellular vesicles up-regulate and directly transfer adherence factors promoting host cell colonization.

Trichomonas vaginalis, a common sexually transmitted parasite that colonizes the human urogenital tract, secretes extracellular vesicles (TvEVs) that are taken up by human cells and are speculated to be taken up by parasites as well. While the crosstalk between TvEVs and human cells has led to insight into host:parasite interactions, roles for TvEVs in infection have largely been one-sided, with little known about the effect of TvEV uptake by T. vaginalis. Approximately 11% of infections are found to be coinfections of multiple T. vaginalis strains. Clinical isolates often differ in their adherence to and cytolysis of host cells, underscoring the importance of understanding the effects of TvEV uptake within the parasite population. To address this question, our lab tested the ability of a less adherent strain of T. vaginalis, G3, to take up fluorescently labeled TvEVs derived from both itself (G3-EVs) and TvEVs from a more adherent strain of the parasite (B7RC2-EVs). Here, we showed that TvEVs generated from the more adherent strain are internalized more efficiently compared to the less adherent strain. Additionally, preincubation of G3 parasites with B7RC2-EVs increases parasite aggregation and adherence to host cells. Transcriptomics revealed that TvEVs up-regulate expression of predicted parasite membrane proteins and identified an adherence factor, heteropolysaccharide binding protein (HPB2). Finally, using comparative proteomics and superresolution microscopy, we demonstrated direct transfer of an adherence factor, cadherin-like protein, from TvEVs to the recipient parasite's surface. This work identifies TvEVs as a mediator of parasite:parasite communication that may impact pathogenesis during mixed infections.

Deep-learning-based motion correction using multichannel MRI data: a study using simulated artifacts in the fastMRI dataset.

Deep learning presents a generalizable solution for motion correction requiring no pulse sequence modifications or additional hardware, but previous networks have all been applied to coil-combined data. Multichannel MRI data provide a degree of spatial encoding that may be useful for motion correction. We hypothesize that incorporating deep learning for motion correction prior to coil combination will improve results. A conditional generative adversarial network was trained using simulated rigid motion artifacts in brain images acquired at multiple sites with multiple contrasts (not limited to healthy subjects). We compared the performance of deep-learning-based motion correction on individual channel images (single-channel model) with that performed after coil combination (channel-combined model). We also investigate simultaneous motion correction of all channel data from an image volume (multichannel model). The single-channel model significantly (p < 0.0001) improved mean absolute error, with an average 50.9% improvement compared with the uncorrected images. This was significantly (p < 0.0001) better than the 36.3% improvement achieved by the channel-combined model (conventional approach). The multichannel model provided no significant improvement in quantitative measures of image quality compared with the uncorrected images. Results were independent of the presence of pathology, and generalizable to a new center unseen during training. Performing motion correction on single-channel images prior to coil combination provided an improvement in performance compared with conventional deep-learning-based motion correction. Improved deep learning methods for retrospective correction of motion-affected MR images could reduce the need for repeat scans if applied in a clinical setting.

Investigations of the function of AMH in granulosa cells in hens.

Anti-mullerian hormone (AMH) plays a crucial role in follicle regulation in mammals by preventing premature primordial follicle activation and restricting follicle development through reduction of FSH sensitivity and inhibition of FSH-induced increase of steroidogenic enzymes. AMH is produced by granulosa cells from growing follicles and expression declines at the time of selection in both mammalian and avian species. The role of AMH in chicken granulosa cells remains unclear, as research is complicated because mammalian AMH is not bioactive in chickens and there is a lack of commercially available chicken AMH. In the current experiments, we used RNA interference to study the role of AMH on markers of follicle development in the presence and absence of FSH. Cultured chicken granulosa cells from 3-5 mm follicles and 6-8 mm follicles, the growing pool from which follicle selection is thought to occur, were used. Transfection with an AMH-specific siRNA significantly reduced AMH mRNA expression in granulosa cells from 3-5 mm and 6-8 mm follicles. Genes of interest were only measured in granulosa cells of 3-5 mm follicles due to low expression of AMH mRNA at the 6-8 mm follicle stage. Knockdown of AMH mRNA did not affect markers of follicle development (follicle stimulating hormone receptor, FSHR; steroidogenic acute regulatory protein, STAR; cytochrome P450 family 11 subfamily A member 1, CYP11A1; bone morphogenetic protein receptor type 2, BMPR2) or FSH responsiveness in granulosa cells from 3-5 mm follicles, indicating that AMH does not regulate follicle development directly by affecting markers of steroidogenesis, FSHR or BMPR2 at this follicle stage in chickens.

Large-scale analysis of sheep rumen metagenome profiles captured by reduced representation sequencing reveals individual profiles are influenced by the environment and genetics of the host.

BACKGROUND: Producing animal protein while reducing the animal's impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years. Genetic selection is one possible path to reduce the environmental impact of livestock production, but these traits are difficult and expensive to measure on many animals. The rumen microbiome may serve as a proxy for these traits due to its role in feed digestion. Restriction enzyme-reduced representation sequencing (RE-RRS) is a high-throughput and cost-effective approach to rumen metagenome profiling, but the systematic (e.g., sequencing) and biological factors influencing the resulting reference based (RB) and reference free (RF) profiles need to be explored before widespread industry adoption is possible. RESULTS: Metagenome profiles were generated by RE-RRS of 4,479 rumen samples collected from 1,708 sheep, and assigned to eight groups based on diet, age, time off feed, and country (New Zealand or Australia) at the time of sample collection. Systematic effects were found to have minimal influence on metagenome profiles. Diet was a major driver of differences between samples, followed by time off feed, then age of the sheep. The RF approach resulted in more reads being assigned per sample and afforded greater resolution when distinguishing between groups than the RB approach. Normalizing relative abundances within the sampling Cohort abolished structures related to age, diet, and time off feed, allowing a clear signal based on methane emissions to be elucidated. Genus-level abundances of rumen microbes showed low-to-moderate heritability and repeatability and were consistent between diets. CONCLUSIONS: Variation in rumen metagenomic profiles was influenced by diet, age, time off feed and genetics. Not accounting for environmental factors may limit the ability to associate the profile with traits of interest. However, these differences can be accounted for by adjusting for Cohort effects, revealing robust biological signals. The abundances of some genera were consistently heritable and repeatable across different environments, suggesting that metagenomic profiles could be used to predict an individual's future performance, or performance of its offspring, in a range of environments. These results highlight the potential of using rumen metagenomic profiles for selection purposes in a practical, agricultural setting.

Deep Learning Reconstruction Enables Prospectively Accelerated Clinical Knee MRI.

Background MRI is a powerful diagnostic tool with a long acquisition time. Recently, deep learning (DL) methods have provided accelerated high-quality image reconstructions from undersampled data, but it is unclear if DL image reconstruction can be reliably translated to everyday clinical practice. Purpose To determine the diagnostic equivalence of prospectively accelerated DL-reconstructed knee MRI compared with conventional accelerated MRI for evaluating internal derangement of the knee in a clinical setting. Materials and Methods A DL reconstruction model was trained with images from 298 clinical 3-T knee examinations. In a prospective analysis, patients clinically referred for knee MRI underwent a conventional accelerated knee MRI protocol at 3 T followed by an accelerated DL protocol between January 2020 and February 2021. The equivalence of the DL reconstruction of the images relative to the conventional images for the detection of an abnormality was assessed in terms of interchangeability. Each examination was reviewed by six musculoskeletal radiologists. Analyses pertaining to the detection of meniscal or ligament tears and bone marrow or cartilage abnormalities were based on four-point ordinal scores for the likelihood of an abnormality. Additionally, the protocols were compared with use of four-point ordinal scores for each aspect of image quality: overall image quality, presence of artifacts, sharpness, and signal-to-noise ratio. Results A total of 170 participants (mean age ± SD, 45 years ± 16; 76 men) were evaluated. The DL-reconstructed images were determined to be of diagnostic equivalence with the conventional images for detection of abnormalities. The overall image quality score, averaged over six readers, was significantly better (P < .001) for the DL than for the conventional images. Conclusion In a clinical setting, deep learning reconstruction enabled a nearly twofold reduction in scan time for a knee MRI and was diagnostically equivalent with the conventional protocol. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Roemer in this issue.

Effect of IGF1 and FSH on the function of granulosa cells from prehierarchal follicles in chickens†.

Insulin-like growth factor 1 (IGF1) is an essential regulator of mammalian follicle development and synergizes with follicle-stimulating hormone (FSH) to amplify its effects. In avian preovulatory follicles, IGF1 increases the expression of genes involved in steroidogenesis and progesterone and inhibin A production. The role of IGF1 in prehierarchal follicles has not been well studied in chickens. The aim of this study was to investigate the role of IGF1 in granulosa cells from prehierarchal follicles and to determine whether IGF1 and FSH synergize to promote follicle development. Granulosa cells of 3-5 and 6-8 mm prehierarchal follicles were cultured with IGF1 (0, 10, 100 ng/mL) in the presence or absence of FSH (0, 10 ng/mL). Cell proliferation, expression of genes important in follicle development (FSHR, IGF1R, AMH, STAR, CYP11A1, INHA, and INHBA), and progesterone production were evaluated following treatment. IGF1 treatment alone significantly increased STAR, CYP11A1, and INHBA mRNA expression and cell proliferation in granulosa cells of 6-8 mm follicles. IGF1 and FSH synergized to increase STAR mRNA expression in 6-8 mm follicles. IGF1 and FSH co-treatment were necessary to increase INHA mRNA expression in 6-8 mm follicles. Although IGF1 significantly increased the expression of genes involved in steroidogenesis, progesterone production in granulosa cells of 6-8 mm follicles was not affected. IGF1 did not affect AMH mRNA expression, although FSH significantly decreased AMH expression in granulosa cells of 3-5 mm follicles. These results suggest that IGF1 may act with FSH to promote follicle selection at the prehierarchal follicle stage.

Molecular Characterization of Polymer Networks.

Polymer networks are complex systems consisting of molecular components. Whereas the properties of the individual components are typically well understood by most chemists, translating that chemical insight into polymer networks themselves is limited by the statistical and poorly defined nature of network structures. As a result, it is challenging, if not currently impossible, to extrapolate from the molecular behavior of components to the full range of performance and properties of the entire polymer network. Polymer networks therefore present an unrealized, important, and interdisciplinary opportunity to exert molecular-level, chemical control on material macroscopic properties. A barrier to sophisticated molecular approaches to polymer networks is that the techniques for characterizing the molecular structure of networks are often unfamiliar to many scientists. Here, we present a critical overview of the current characterization techniques available to understand the relation between the molecular properties and the resulting performance and behavior of polymer networks, in the absence of added fillers. We highlight the methods available to characterize the chemistry and molecular-level properties of individual polymer strands and junctions, the gelation process by which strands form networks, the structure of the resulting network, and the dynamics and mechanics of the final material. The purpose is not to serve as a detailed manual for conducting these measurements but rather to unify the underlying principles, point out remaining challenges, and provide a concise overview by which chemists can plan characterization strategies that suit their research objectives. Because polymer networks cannot often be sufficiently characterized with a single method, strategic combinations of multiple techniques are typically required for their molecular characterization.

Combining host and rumen metagenome profiling for selection in sheep: prediction of methane, feed efficiency, production, and health traits.

BACKGROUND: Rumen microbes break down complex dietary carbohydrates into energy sources for the host and are increasingly shown to be a key aspect of animal performance. Host genotypes can be combined with microbial DNA sequencing to predict performance traits or traits related to environmental impact, such as enteric methane emissions. Metagenome profiles were generated from 3139 rumen samples, collected from 1200 dual purpose ewes, using restriction enzyme-reduced representation sequencing (RE-RRS). Phenotypes were available for methane (CH4) and carbon dioxide (CO2) emissions, the ratio of CH4 to CH4 plus CO2 (CH4Ratio), feed efficiency (residual feed intake: RFI), liveweight at the time of methane collection (LW), liveweight at 8 months (LW8), fleece weight at 12 months (FW12) and parasite resistance measured by faecal egg count (FEC1). We estimated the proportion of phenotypic variance explained by host genetics and the rumen microbiome, as well as prediction accuracies for each of these traits. RESULTS: Incorporating metagenome profiles increased the variance explained and prediction accuracy compared to fitting only genomics for all traits except for CO2 emissions when animals were on a grass diet. Combining the metagenome profile with host genotype from lambs explained more than 70% of the variation in methane emissions and residual feed intake. Predictions were generally more accurate when incorporating metagenome profiles compared to genetics alone, even when considering profiles collected at different ages (lamb vs adult), or on different feeds (grass vs lucerne pellet). A reference-free approach to metagenome profiling performed better than metagenome profiles that were restricted to capturing genera from a reference database. We hypothesise that our reference-free approach is likely to outperform other reference-based approaches such as 16S rRNA gene sequencing for use in prediction of individual animal performance. CONCLUSIONS: This paper shows the potential of using RE-RRS as a low-cost, high-throughput approach for generating metagenome profiles on thousands of animals for improved prediction of economically and environmentally important traits. A reference-free approach using a microbial relationship matrix from log10 proportions of each tag normalized within cohort (i.e., the group of animals sampled at the same time) is recommended for future predictions using RE-RRS metagenome profiles.

Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5-methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA in T. vaginalis is associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.

Feeding level is associated with altered liver transcriptome and follicle selection in hen†.

Genetic selection for particular traits in domestic animals may have altered the optimal feedback regulation among systems regulating appetite, growth, and reproduction. Broiler breeder chickens have been selected for fast and efficient growth and, unless feed restricted, consume excessively resulting in poor reproductive efficiency. We examined the effect of dietary treatment in full-fed and restricted-fed broiler breeder hens on ovarian responses, liver morphology, and transcriptome associated with reproductive function. Although full-fed broiler breeder hens had lower egg production (P < 0.01), the total number of ovarian follicles >8 mm (P < 0.01), 6-8 mm (P < 0.03), and 3-5 mm (P < 0.04) were greater in full-fed hens compared to restricted-fed hens. There was a large amount of lipid accumulation in the liver of full-fed hens and differential gene analysis yielded 120 genes that were differentially expressed >2-fold in response to feeding level (P < 0.01; false discovery rate < 0.05). Elevated T3 may indicate that general metabolism was affected by diet and GHR (P < 0.01) and insulin like growth factor 1 (IGF1) (P < 0.04) mRNA expression were both greater in the liver of full-fed hens as compared to restricted-fed hens. It is likely that selection for increased growth, associated with enhanced activity of the IGF1 system, has altered nutritional coupling of feed intake to follicle development.

Deep Learning Reconstruction Enables Highly Accelerated Biparametric MR Imaging of the Prostate.

BACKGROUND: Early diagnosis and treatment of prostate cancer (PCa) can be curative; however, prostate-specific antigen is a suboptimal screening test for clinically significant PCa. While prostate magnetic resonance imaging (MRI) has demonstrated value for the diagnosis of PCa, the acquisition time is too long for a first-line screening modality. PURPOSE: To accelerate prostate MRI exams, utilizing a variational network (VN) for image reconstruction. STUDY TYPE: Retrospective. SUBJECTS: One hundred and thirteen subjects (train/val/test: 70/13/30) undergoing prostate MRI. FIELD STRENGTH/SEQUENCE: 3.0 T; a T2 turbo spin echo (TSE) T2-weighted image (T2WI) sequence in axial and coronal planes, and axial echo-planar diffusion-weighted imaging (DWI). ASSESSMENT: Four abdominal radiologists evaluated the image quality of VN reconstructions of retrospectively under-sampled biparametric MRIs (bp-MRI), and standard bp-MRI reconstructions for 20 test subjects (studies). The studies included axial and coronal T2WI, DWI B50 seconds/mm2 and B1000 seconds/mm (4-fold T2WI, 3-fold DWI), all of which were evaluated separately for image quality on a Likert scale (1: non-diagnostic to 5: excellent quality). In another 10 test subjects, three readers graded lesions on bp-MRI-which additionally included calculated B1500 seconds/mm2 , and apparent diffusion coefficient map-according to the Prostate Imaging Reporting and Data System (PI-RADS v2.1), for both VN and standard reconstructions. Accuracy of PI-RADS ≥3 for clinically significant cancer was computed. Projected scan time of the retrospectively under-sampled biparametric exam was also computed. STATISTICAL TESTS: One-sided Wilcoxon signed-rank test was used for comparison of image quality. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for lesion detection and grading. Generalized estimating equation with cluster effect was used to compare differences between standard and VN bp-MRI. A P-value of <0.05 was considered statistically significant. RESULTS: Three of four readers rated no significant difference for overall quality between the standard and VN axial T2WI (Reader 1: 4.00 ± 0.56 (Standard), 3.90 ± 0.64 (VN) P = 0.33; Reader 2: 4.35 ± 0.74 (Standard), 3.80 ± 0.89 (VN) P = 0.003; Reader 3: 4.60 ± 0.50 (Standard), 4.55 ± 0.60 (VN) P = 0.39; Reader 4: 3.65 ± 0.99 (Standard), 3.60 ± 1.00 (VN) P = 0.38). All four readers rated no significant difference for overall quality between standard and VN DWI B1000 seconds/mm2 (Reader 1: 2.25 ± 0.62 (Standard), 2.45 ± 0.75 (VN) P = 0.96; Reader 2: 3.60 ± 0.92 (Standard), 3.55 ± 0.82 (VN) P = 0.40; Reader 3: 3.85 ± 0.72 (Standard), 3.55 ± 0.89 (VN) P = 0.07; Reader 4: 4.70 ± 0.76 (Standard); 4.60 ± 0.73 (VN) P = 0.17) and three of four readers rated no significant difference for overall quality between standard and VN DWI B50 seconds/mm2 (Reader 1: 3.20 ± 0.70 (Standard), 3.40 ± 0.75 (VN) P = 0.98; Reader 2: 2.85 ± 0.81 (Standard), 3.00 ± 0.79 (VN) P = 0.93; Reader 3: 4.45 ± 0.72 (Standard), 4.05 ± 0.69 (VN) P = 0.02; Reader 4: 4.50 ± 0.69 (Standard), 4.45 ± 0.76 (VN) P = 0.50). In the lesion evaluation study, there was no significant difference in the number of PI-RADS ≥3 lesions identified on standard vs. VN bp-MRI (P = 0.92, 0.59, 0.87) with similar sensitivity and specificity for clinically significant cancer. The average scan time of the standard clinical biparametric exam was 11.8 minutes, and this was projected to be 3.2 minutes for the accelerated exam. DATA CONCLUSION: Diagnostic accelerated biparametric prostate MRI exams can be performed using deep learning methods in <4 minutes, potentially enabling rapid screening prostate MRI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

Trichomonas vaginalis extracellular vesicles are internalized by host cells using proteoglycans and caveolin-dependent endocytosis.

Trichomonas vaginalis, a human-infective parasite, causes the most prevalent nonviral sexually transmitted infection worldwide. This pathogen secretes extracellular vesicles (EVs) that mediate its interaction with host cells. Here, we have developed assays to study the interface between parasite EVs and mammalian host cells and to quantify EV internalization by mammalian cells. We show that T. vaginalis EVs interact with glycosaminoglycans on the surface of host cells and specifically bind to heparan sulfate (HS) present on host cell surface proteoglycans. Moreover, competition assays using HS or removal of HS from the host cell surface strongly inhibit EV uptake, directly demonstrating that HS proteoglycans facilitate EV internalization. We identified an abundant protein on the surface of T. vaginalis EVs, 4-α-glucanotransferase (Tv4AGT), and show using isothermal titration calorimetry that this protein binds HS. Tv4AGT also competitively inhibits EV uptake, defining it as an EV ligand critical for EV internalization. Finally, we demonstrate that T. vaginalis EV uptake is dependent on host cell cholesterol and caveolin-1 and that internalization proceeds via clathrin-independent, lipid raft-mediated endocytosis. These studies reveal mechanisms used to drive host:pathogen interactions and further our understanding of how EVs are internalized by target cells to allow cross-talk between different cell types.

Artificial Intelligence for MR Image Reconstruction: An Overview for Clinicians.

Artificial intelligence (AI) shows tremendous promise in the field of medical imaging, with recent breakthroughs applying deep-learning models for data acquisition, classification problems, segmentation, image synthesis, and image reconstruction. With an eye towards clinical applications, we summarize the active field of deep-learning-based MR image reconstruction. We review the basic concepts of how deep-learning algorithms aid in the transformation of raw k-space data to image data, and specifically examine accelerated imaging and artifact suppression. Recent efforts in these areas show that deep-learning-based algorithms can match and, in some cases, eclipse conventional reconstruction methods in terms of image quality and computational efficiency across a host of clinical imaging applications, including musculoskeletal, abdominal, cardiac, and brain imaging. This article is an introductory overview aimed at clinical radiologists with no experience in deep-learning-based MR image reconstruction and should enable them to understand the basic concepts and current clinical applications of this rapidly growing area of research across multiple organ systems.

Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis.

T. vaginalis, a human-infective parasite, causes the most common nonviral sexually transmitted infection (STI) worldwide and contributes to adverse inflammatory disorders. The immune response to T. vaginalis is poorly understood. Neutrophils (polymorphonuclear cells [PMNs]) are the major immune cell present at the T. vaginalis-host interface and are thought to clear T. vaginalis. However, the mechanism of PMN clearance of T. vaginalis has not been characterized. We demonstrate that human PMNs rapidly kill T. vaginalis in a dose-dependent, contact-dependent, and neutrophil extracellular trap (NET)-independent manner. In contrast to phagocytosis, we observed that PMN killing of T. vaginalis involves taking "bites" of T. vaginalis prior to parasite death, using trogocytosis to achieve pathogen killing. Both trogocytosis and parasite killing are dependent on the presence of PMN serine proteases and human serum factors. Our analyses provide the first demonstration, to our knowledge, of a mammalian phagocyte using trogocytosis for pathogen clearance and reveal a novel mechanism used by PMNs to kill a large, highly motile target.

A school-based, interprofessional approach to sustaining oral health on an Island community.

A school-based oral health promotion program was established on a Bahamian island that lacks access to dental care. An interprofessional team of dental hygiene (DH) and occupational therapy (OT) students and faculty delivered an annual service program from 2016 to 2018 based on the Ecological Model of School-Based Health Promotion. The interprofessional team provided oral preventative services and class-based lessons to children to reinforce positive oral health behaviors. Efforts to sustain the program involved partnering with the Bahamian community stakeholders to expand networks of influence, developing effective communication systems, and integrating oral health into the school curriculum. The interprofessional approach enabled a sustained and comprehensive program. This report describes the unique DH and OT interprofessional collaboration and program sustainability efforts.

Gravity in Midfacial Aging: A 3-Dimensional Study.

BACKGROUND: Volume loss and volume descent are complementary aspects of facial aging, although the respective contribution of each is unclear. OBJECTIVES: The aim of this study was to quantify in 3 dimensions the effects of gravity on the midface in both upright and supine positions in an older and a younger group of patients. METHODS: A prospective study was undertaken of 53 female patients who had not undergone treatment with dermal fillers or facial cosmetic surgery. Three-dimensional photography with a VECTRA H1 camera (Canfield Scientific, Fairfield, NJ) was taken in supine and sitting positions. Volume shifts and displacement of structures in 3 dimensions were measured and analyzed. RESULTS: Morphologically, upon shifting from sitting to supine position, the tail of the brow elevated, the tear trough filled, the buccal and malar fat shifted posteriosuperiorly, the earlobe decreased in height, the nasiolabial folds and marionette lines diminished, the modiolus shifted laterally, and the jowl diminished. Volumetric analysis revealed that the infraorbital region increased in volume by a mean [SD] of 0.59 [0.55] mL, the tear trough by 0.22 [0.19] mL, and the malar region by 1.2 [1.06] mL. With subjects in the supine position, all facial topographic landmarks displaced significantly from sitting position. CONCLUSIONS: Facial aging in this cohort was predominantly due to tissue descent rather than volume loss. Reversal of the gravitational force restores the 3D position of the facial subunits and leads to volumization in desirable locations that approximates a more youthful appearance. The volume restored via redistribution of facial fat is comparable to that typically injected during direct volume transfer procedures.

Mechanochemical Regulation of Oxidative Addition to a Palladium(0) Bisphosphine Complex.

Here, we report the effect of force applied to the biaryl backbone of a bisphosphine ligand on the rate of oxidative addition of bromobenzene to a ligand-coordinated palladium center. Local compressive and tensile forces on the order of 100 pN were generated using a stiff stilbene force probe. A compressive force increases the rate of oxidative addition, whereas a tensile force decreases the rate, relative to that of the parent complex of strain-free ligand. Rates vary by a factor of ∼6 across ∼340 pN of force applied to the complexes. The crystal structures and DFT calculations support that force-induced perturbation of the geometry of the reactant is negligible. The force-rate relationship observed is mainly attributed to the coupling of force to nuclear motion comprising the reaction coordinate. These observations inform the development of catalysts whose activity can be tuned by an external force that is adjusted within a catalytic cycle.

Using Deep Learning to Accelerate Knee MRI at 3 T: Results of an Interchangeability Study.

OBJECTIVE. Deep learning (DL) image reconstruction has the potential to disrupt the current state of MRI by significantly decreasing the time required for MRI examinations. Our goal was to use DL to accelerate MRI to allow a 5-minute comprehensive examination of the knee without compromising image quality or diagnostic accuracy. MATERIALS AND METHODS. A DL model for image reconstruction using a variational network was optimized. The model was trained using dedicated multisequence training, in which a single reconstruction model was trained with data from multiple sequences with different contrast and orientations. After training, data from 108 patients were retrospectively undersampled in a manner that would correspond with a net 3.49-fold acceleration of fully sampled data acquisition and a 1.88-fold acceleration compared with our standard twofold accelerated parallel acquisition. An interchangeability study was performed, in which the ability of six readers to detect internal derangement of the knee was compared for clinical and DL-accelerated images. RESULTS. We found a high degree of interchangeability between standard and DL-accelerated images. In particular, results showed that interchanging the sequences would produce discordant clinical opinions no more than 4% of the time for any feature evaluated. Moreover, the accelerated sequence was judged by all six readers to have better quality than the clinical sequence. CONCLUSION. An optimized DL model allowed acceleration of knee images that performed interchangeably with standard images for detection of internal derangement of the knee. Importantly, readers preferred the quality of accelerated images to that of standard clinical images.

Protein Palmitoylation Plays an Important Role in Trichomonas vaginalis Adherence.

The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. As an obligate extracellular pathogen, adherence to epithelial cells is critical for parasite survival within the human host and a better understanding of this process is a prerequisite for the development of therapies to combat infection. In this sense, recent work has shown S-acylation as a key modification that regulates pathogenesis in different protozoan parasites. However, there are no reports indicating whether this post-translational modification is a mechanism operating in T. vaginalis In order to study the extent and function of S-acylation in T. vaginalis biology, we undertook a proteomic study to profile the full scope of S-acylated proteins in this parasite and reported the identification of 363 proteins involved in a variety of biological processes such as protein transport, pathogenesis related and signaling, among others. Importantly, treatment of parasites with the palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in parasite: parasite aggregation as well as adherence to host cells suggesting that palmitoylation could be modifying proteins that are key regulators of Trichomonas vaginalis pathogenesis.