Comprehensive analyses with radiological and biological markers of breast cancer on contrast-enhanced chest CT: a single center experience using dual-layer spectral detector CT.

OBJECTIVES: To evaluate the predictive value of virtual monoenergetic images (VMIs) by assessing tumor conspicuity on dual-layer spectral detector CT (SDCT) and correlate tumor conspicuity on VMI with prognostic biomarkers in patients with breast cancer. METHODS: Sixty-four patients underwent arterial phase and 90-s delayed phase dual-layer SDCT. A retrospective tumor conspicuity analysis of 14 benign tumors and 65 breast cancers was performed using conventional images (CIs) and VMI at 40 keV (VMI40) on arterial and delayed phase scans (CIART, VMI40ART, CIDE, VMI40DE). Mean Hounsfield units (HU) of tumors were measured on VMI40ART and VMI40DE. A receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic accuracy between image sets. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 levels were evaluated using histopathology. Correlations between VMI analyses and histological characteristics of cancers were analyzed. RESULTS: Cancers on VMI40 had a significantly higher conspicuity score and mean HU than benign tumors (p < 0.001). VMI40DE showed the highest conspicuity for cancers (mean, 3.79) and the greatest area under the ROC curve (0.817; 95% confidence interval 0.745-0.889). VMI40DE yielded significantly higher mean HU for cancers than VMI40ART (p < 0.001). The conspicuity score and mean HU on VMI40ART were significantly higher in cancers with ER negativity, PR negativity, and Ki67 positivity (p < 0.05). CONCLUSIONS: VMI40DE may be useful in the diagnosis of breast cancers due to higher tumor conspicuity and better enhancement than VMI40ART. VMI40ART may be beneficial for the prediction of poor breast cancer prognoses. KEY POINTS: • VMI40 improved conspicuity of breast cancer than CI. • VMI40DEyielded higher diagnostic performance of breast cancer than VMI40ART. • VMI40ARThas an additional benefit in terms of prognosis prediction in patients with breast cancers.

One-Minute Ultrafast Brain MRI With Full Basic Sequences: Can It Be a Promising Way Forward for Pediatric Neuroimaging?

OBJECTIVE. The long scan time of brain MRI is a major drawback that limits its clinical use for evaluating pediatric patients who are inherently prone to motion and frequently require sedatives. This study investigated the clinical feasibility of a 1-minute ultrafast brain MRI protocol in pediatric patients by assessing its image quality in comparison with that of routine brain MRI. MATERIALS AND METHODS. Twenty-three patients were enrolled who underwent 1-minute ultrafast MRI and routine brain MRI protocols including five essential sequences (T1-weighted imaging, T2-weighted imaging, DWI, FLAIR, and T2*-weighted imaging). Total scan time for the same image contrast levels was 1 minute 11 seconds for ultrafast MRI versus 9 minutes 51 seconds for routine brain MRI. Two readers independently reviewed all images from the two MRI protocols and graded the image quality on a 4-point Likert scale. The Wilcoxon signed rank test was used to compare the readers' ratings; interobserver agreement between the readers was also assessed. RESULTS. Although the mean scores of overall image quality and anatomic delineation in ultrafast brain MR images were significantly lower than those in routine brain MR images, ultrafast brain MRI showed sufficient overall image quality and anatomic delineation with more than 2 points on the 4-point scale. CONCLUSION. The 1-minute ultrafast brain MRI protocol showed at least sufficient image quality compared with routine brain MRI. Therefore, 1-minute ultrafast brain MRI can be a viable first-line neuroimaging study for pediatric patients because of its shorter scan time, absence of radiation hazard, and reduced sedation requirements.

Initial clinical experience of synthetic MRI as a routine neuroimaging protocol in daily practice: A single-center study.

BACKGROUND AND PURPOSE: We investigated the clinical feasibility of synthetic MRI with a 4-min single scan using a 48-channel head coil as a routine neuroimaging protocol in daily practice by assessing its diagnostic image quality. METHODS: We retrospectively reviewed the imaging data of 89 patients who underwent routine brain MRI using synthetic MRI acquisition between February 2017 and April 2017. Image quality assessments were performed by two independent readers on synthetic T1 fluid-attenuated inversion recovery (FLAIR), T2-weighted, T2 FLAIR, and phase-sensitive inversion recovery sequences acquired using multiple-dynamic multiple-echo imaging. Interobserver reliability between the two readers was assessed using kappa (κ) statistics. RESULTS: On a 4-point assessment scale, the overall image quality and anatomical delineation provided by synthetic brain MRI were found to be good with scores of more than 3 points for all sequences except for the T2 FLAIR sequence. The synthetic T2 FLAIR sequence provided sufficient image quality but showed more pronounced artifacts, especially the CSF pulsation artifact and linear hyperintensity along the brain surface. Interobserver agreement for evaluating image quality of all synthetic sequences was good to excellent (κ, 0.61-0.99; P < 0.001). CONCLUSION: Synthetic MRI can be acceptable as a routine clinical neuroimaging protocol with a short scan time. It can be helpful to design customized and flexible neuroimaging protocols for each institution.

Association between aortic valvular calcification and characteristics of the aortic valve in patients with bicuspid aortic valve stenosis.

BACKGROUND: Aortic valve calcification quantification using cardiac computed tomography (CCT) is a reliable marker for aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) disease. PURPOSE: To determine the association of Agatston aortic valve calcium score (AVCS) with morphological and hemodynamic characteristics of BAV and define cut-off AVCS for optimizing the grade of AS in patients with bicuspid AS. MATERIAL AND METHODS: This study included 161 BAV patients with AS regardless of aortic regurgitation who underwent transthoracic echocardiography and CCT. BAVs were classified according to orientation of cusps and presence of raphe. Associations of AVCS with characteristics of BAV morphology and functional variables were determined by linear regression analysis. Area under the receiver operating characteristic curve (AUC) was used to determine the cut-off AVCS greater than which the diagnosis of severe AS was optimized. RESULTS: AVCS was significantly different according to sex ( P < 0.001), AS severity ( P < 0.001), type of valvular dysfunction ( P = 0.011), and orientation of cusps ( P = 0.028). Multiple linear regression showed that AVCS was significantly associated with sex (estimate = -0.583, P < 0.001) and AS severity (estimate = 0.817, P < 0.001). AVCS was a predictor for severe AS with AUC of 0.80 in both women ( P = 0.002) and men ( P < 0.001). Its cut-off value was 1423 Agatston unit (AU) in women and 2573 AU in men. CONCLUSIONS: In patients with bicuspid AS, AVCS was significantly higher in men and those with severe AS. However, AVCS was not significantly associated with morphological characteristics of BAV or the type of valvular dysfunction.

AMPK Alters Detrusor Contractility During Emptying in Normal Bladder and Hypertrophied Bladder with Partial Bladder Outlet Obstruction via CaMKKß.

AMP-activated protein kinase (AMPK) has been implicated in contractility changes in bladders with partial bladder outlet obstruction (PBOO), but the role of AMPK in the contractile response of normal bladder remains unclear. We investigated the phosphorylation of AMPKα and expression of the involved upstream AMPK kinases (AMPKKs) in a model of bladders with PBOO and sought to determine whether the pharmacological inhibition of these two factors affected detrusor contractility in normal bladders, using female Sprague-Dawley rats. Cystometry and Western blot analysis were performed in rats that were subjected to PBOO induction or a sham operation. Cystometry was performed in normal rats that received selective inhibitors of AMPKα and Ca2+/calmodulin-dependent protein kinase kinase (CaMKKß) (compound C and STO-609, respectively) at doses determined in the experiments. In the PBOO bladders, bladder weight and micturition pressure (MP) were higher and AMPKα phosphorylation (T172) and CaMKKß expression was significantly reduced. Compound C and STO-609 increased MP. The increased contractile response in bladders with PBOO-induced hypertrophy was related to decreased CaMKKß/AMPK signaling activity, and the pharmacological inhibition of this pathway in normal bladders increased detrusor contractility, implying a role of CaMKKß/AMPK signaling in the bladder in the regulation of detrusor contractility.

Cervical Lymph Nodes Detected by F-18 FDG PET/CT in Oncology Patients: Added Value of Subsequent Ultrasonography for Determining Nodal Metastasis.

Background and Objectives: To investigate the diagnostic performance of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and subsequent ultrasonography (US) for determining cervical nodal metastasis in oncology patients. Materials and Methods: Fifty-nine cervical lymph nodes (LNs) initially detected by PET/CT with subsequent neck US were included in this retrospective study. All LNs were subjected to US-guided fine-needle aspiration or core needle biopsy. The maximum standardized uptake value (SUVmax) and sonographic features were assessed. Results: Forty-three of 59 cervical LNs detected by PET/CT were malignant. PET/CT alone showed a highest diagnostic value for metastatic LNs with 81.4% sensitivity, 68.8% specificity, and 78% accuracy when SUVmax ≥5.8 was applied as an optimal cut-off value. Combined PET/CT and subsequent US diagnoses for determining nodal metastasis showed the following diagnostic performance: 81.4% sensitivity, 87.5% specificity, and 83.1% accuracy. There was a significant difference in the diagnostic performance between the two diagnostic imaging approaches (p = 0.006). Conclusions: Combined diagnosis using subsequent US showed a significantly higher diagnostic performance for determining nodal metastasis in the neck. Therefore, we believe that our proposed diagnostic strategy using subsequent US can be helpful in evaluating cervical LNs on PET/CT. Moreover, our results clarify the need for US-guided tissue sampling in oncology patients.

Usefulness of abbreviated breast MRI screening for women with a history of breast cancer surgery.

PURPOSE: We investigated the usefulness of abbreviated breast MRI (AB-MRI), including fat-suppressed T2-weighted imaging, pre- and postcontrast image acquisition, and subtracted maximum-intensity projection imaging, for the screening of women with a history of breast cancer surgery. METHODS: Between October 2014 and March 2016, a total of 799 AB-MRI examinations were performed for 725 women with a history of breast cancer surgery. The image acquisition time was 8.5 min. Screening mammography, ultrasound, and AB-MRI were generally performed around the same time. The cancer detection rate, positive predictive values for recall and biopsy, sensitivity and specificity of screening MRI, and rate of malignancy belonging to each breast imaging reporting and data system (BI-RADS) category were assessed. RESULTS: AB-MRI detected 12 malignancies in 12 women (15.0 cancers per 1000 cases). Seven of these 12 malignancies were initially invisible on ultrasound and mammography, although subsequent targeted ultrasound revealed lesions corresponding to the MRI-detected lesions. The positive predictive values for recall and biopsy and sensitivity and specificity values for screening MRI were 12.4, 61.5, 100, and 89.2%, respectively. The rates of malignancies belonging to categories 1, 2, 3, and 4 of the BI-RADS were 0, 0, 4.8, and 57.1%, respectively. CONCLUSIONS: The diagnostic performance of screening AB-MRI for women with a history of breast cancer surgery is acceptable, with the advantages of short examination and interpretation times and low costs. Thus, it could be used as a main screening modality that may replace conventional imaging in breast cancer survivors.

Correction to: Usefulness of abbreviated breast MRI screening for women with a history of breast cancer surgery.

In the original publication of the article, the acknowledgment section was missed out inadvertently. The acknowledgement section is below.

Improved Opacification of a Suboptimally Enhanced Pulmonary Artery in Chest CT: Experience Using a Dual-Layer Detector Spectral CT.

OBJECTIVE: The objective of our study was to evaluate the quality of virtual monoenergetic imaging (VMI) from dual-layer detector spectral CT and the effect of virtual monoenergetic images obtained at low energies on the detection of pulmonary embolism (PE) in patients with a suboptimally enhanced pulmonary artery on chest CT. MATERIALS AND METHODS: Of 1552 consecutive chest CT examinations performed with dual-layer detector spectral CT using a routine protocol with a tube voltage of 120 kVp, 79 examinations with suboptimal enhancement of the pulmonary artery (i.e., mean attenuation of pulmonary artery ≤ 180 HU) were included. The mean attenuation of the pulmonary artery, noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of virtual monoenergetic images obtained at 40-200 keV were compared with those of the conventional 120-kVp images. The virtual monoenergetic images with the best CNR were compared with the 120-kVp images with regard to subjective image quality and diagnostic accuracy for detecting PE. RESULTS: Sufficient attenuation of the pulmonary artery (> 180 HU) was obtained using VMI for 78 of the 79 examinations. The noise levels of the virtual monoenergetic images were gradually increased with decreasing energy level (i.e., kiloelectron volt setting). The CNR and SNR of virtual monoenergetic images at 40-65 keV were significantly higher (both, p < 0.001) than the CNR and SNR of the 120-kVp images. The CNR was the highest at 40 keV for all cases. Diagnostic accuracy for detecting PE was significantly higher for 40-keV images (reader 1: AUC = 0.992, p = 0.033; reader 2: AUC = 0.986, p = 0.043) than for 120-kVp images (reader 1, AUC = 0.911; reader 2, AUC = 0.933). The subjective quality was not different between these two images. CONCLUSION: In chest CT examinations in which the pulmonary artery is suboptimally enhanced, obtaining virtual monoenergetic images at a low energy setting using dual-layer detector spectral CT allows sufficient attenuation of the pulmonary artery to be achieved while preserving image quality and increasing diagnostic performance for detecting PE.

Metaplastic spindle cell carcinoma of the breast in a patient with neurofibromatosis type 1.

We report a unique case of a 67-year-old woman with neurofibromatosis type 1, who was also diagnosed with metaplastic spindle cell carcinoma of the left breast. She had many neurofibromatosis lesions on her body, as well as the mass in the left breast. After the breast mass was diagnosed as a malignant mesenchymal tumor by core needle biopsy, the patient underwent left modified radical mastectomy. Subsequently, the pathological analysis of the tumor showed it to be a metaplastic spindle cell carcinoma. The co-occurrence of neurofibromatosis type 1 and breast cancer, in particular metaplastic spindle cell carcinoma, is very rare.

Specificity and putative mode of action of a mosquito larvicidal toxin from the bacterium Xenorhabdus innexi.

Reduction of mosquito-borne diseases relies, in part, on the use of synthetic pesticides to control pest mosquitoes. This reliance has led to genetic resistance, environmental contamination and the nondiscriminatory elimination of both pest and non-pest species. To expand our options for control, we screened entomopathogenic bacteria for potential larvicidal activity. A lipopeptide from the bacterium, Xenorhabdus innexi, was discovered that displayed potent larvicidal activity. The LC50s of the lipopeptide towards Aedes aegypti, Culex pipiens and Anopheles gambiae larvae were 1.81, 1.25 and 1.86 parts-per-million, respectively. No mortality was observed in other insect species tested. The putative mode of action of the lipopeptide suggested that after orally ingestion, it bound to the apical membrane of anterior midgut cells and created pores in the cellular membranes. The rapid neutralization of midgut pH suggested the pores disabled the H+-V-ATPase on the basal membrane and led to epithelial cell death. Specificity and toxicity towards mosquito larvae and the unique mode of action makes this lipopeptide a potentially attractive bacterial insecticide for control of mosquitoes.

Interpretations of diffusion-weighted MR imaging by radiology residents in the emergency department: is diagnostic performance influenced by the level of residency training?

BACKGROUND: To evaluate the diagnostic performance of radiology residents' interpretations for diffusion-weighted MR imaging (DWI) in the emergency department at different levels of residency training. METHOD AND MATERIALS: A total of 160 patients who underwent DWI with acute neurologic symptoms were included in this retrospective study with an institutional review board approval. Four radiology residents with different training years and one attending neuroradiologist independently assessed the DWI results. Discordances between the results of residents and attending neuroradiologist were classified as follows: false positive (FP) and false negative (FN). We also evaluated the diagnostic performance of four residents according to the reference standard. RESULTS: Overall, the concordance rate was 84.8 %, with a 15.2 % overall discordance rate. There were 83 FN results. The most common misses were small vessel disease (n = 55), acute focal infarction (n = 10), diffuse axonal injury (n = 6), solitary mass (n = 5), extraaxial hemorrhages (n = 3), posterior reversible encephalopathy syndrome (n = 2), and postictal change (n = 2). Fourteen FP results were interpreted as hemorrhage and acute infarction. The 4th year resident exhibited the highest diagnostic performance, and the level of training had a significant influence on the rates of concordance (P < 0.05). Interobserver reliability was good between the interpretations of the residents and the final interpretations of the attending neuroradiologists. CONCLUSION: The level of resident training had a significant effect on their diagnostic performance, and good interobserver reliability was noted between the results of the residents and attending neuroradiologist.

Superior Labral Cleft after Superior Labral Anterior-to-Posterior Tear Repair: CT Arthrographic Features and Correlation with Clinical Outcome.

PURPOSE: To evaluate the presence of a superior labral cleft at postoperative computed tomographic (CT) arthrography after superior labral anterior-to-posterior lesion (SLAP) repair and to correlate CT arthrographic appearance with clinical outcomes. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. Fifty-six patients who underwent CT arthrography after arthroscopic SLAP repair were included. Two musculoskeletal radiologists retrospectively reviewed CT arthrographic images for the presence, size, location, direction, and shape of a superior labral cleft, which was defined as a detectable contrast material-filled focal discontinuity of the labrum within anchor fixation sites of the glenoid. In addition, the glenoid osteolysis ratio was calculated on the basis of the CT arthrographic images. Clinical outcome was evaluated with use of the American Shoulder and Elbow Surgeons (ASES) scoring system. Continuous variables, such as patient age, interval between imaging and surgery, ASES score, and osteolysis ratio, were compared by using the Mann-Whitney U test. RESULTS: A superior labral cleft was observed in 27 of the 56 patients (48%). The mean width and depth of the superior labral clefts was 2.1 mm ± 1.1 and 2.8 mm ± 0.8, respectively. The superior labral clefts extended posterior to the biceps anchor in 16 of the 27 patients (59%), were curved medially in 24 (89%), and had a smooth margin in 22 (81%). No significant association was observed between the presence of a superior labral cleft and the ASES score (P = .805) or patient age (P = .290). Superior labral clefts were observed more commonly in cases with a long interval since surgery (P = .007) and a high osteolysis ratio (P = .011). CONCLUSION: Superior labral clefts are frequently observed on CT arthrographic images after arthroscopic SLAP repair and do not correlate with clinical outcome.

Pulmonary Tuberculosis in Patients With Emphysema: Computed Tomography Findings.

OBJECTIVE: To evaluate the computed tomography (CT) findings and clinical characteristics of pulmonary tuberculosis (TB) in patients with emphysema, compared with those without emphysema. MATERIALS AND METHODS: Thirty-nine patients (M:F = 36:3; mean age, 64.8 years) who were diagnosed with chronic obstructive pulmonary disease and had emphysema in pretreatment chest CT scans were included in this study (emphysema group). Their clinical presentation, laboratory findings, and CT findings were compared with those of 57 pulmonary TB patients without chronic obstructive pulmonary disease and emphysema (M:F = 52:5; mean age, 64.3 years) (nonemphysema group). RESULTS: Fever was a more frequent clinical presentation and the C-reactive protein level was higher in the emphysema group. Among CT findings, consolidation and ground-glass opacity were seen more frequently in the emphysema group (82% and 69% vs 42% and 19%, respectively, P < 0.001). Consolidation was more often nonsegmental than lobular or segmental. Tree-in-bud appearance was less frequently noted in the emphysema group (36% vs 79%, P < 0.001). The location of main lesions (upper lung vs middle/lower lung) was not different between the 2 groups. CONCLUSIONS: Pulmonary TB in emphysema patients often shows bacterial pneumonia-like features, that is, presence of consolidation and ground-glass opacity and lack of bronchogenic spread on chest CT scans, combined with the presence of fever and a high C-reactive protein level. Sputum smear for acid-fast bacteria should be performed early in emphysema patients with pneumonia in TB-endemic areas.

NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine.

MFG-E8 (also known as lactadherin), which is a secreted glycoprotein from a variety of cell types, possesses two EGF domains and tandem C domains with sequence homology to that of blood coagulation proteins factor V and factor VIII. MFG-E8 binds to phosphatidylserine (PS) in membranes with high affinity. We have recently shown that the C2 domain of MFG-E8 bears more specificity toward PS when compared with phosphatidylcholine (PC), another phospholipid thought to be involved in the immune function of phagocytes. In our current study, we have determined the solution structure of the C2 domain by nuclear magnetic resonance (NMR) spectroscopy, and characterized the molecular basis of binding between the C2 domain and PS by (31)P-NMR spectroscopy. Furthermore, we also verified that that positively charged and aromatic residues clustered in loops 1-3 of the C2 domain play key roles in recognizing PS in apoptotic cells.

The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase.

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. AANAT, which is expressed in the pineal gland, retina, and various other tissues, catalyzes the conversion of serotonin to N-acetylserotonin and is the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AANAT can be used to treat patients with circadian rhythm disorders that are associated with specific circadian rhythm alterations, such as shift work disorder. In the present study, we screened modulators of AANAT activity from the water extracts of medicinal plants. Among the 267 tested medicinal plant extracts, Myricae Cortex (Myrica rubra), Perillae Herba (Perilla sikokiana), and Eriobotryae Folium (Eriobotrya japonica) showed potent inhibition of AANAT activity. Myricetin (5,7,3',4',5'-pentahydroxyflavonol), a main component of the Myricae Cortex, strongly inhibited the activity of AANAT and probably block the access to the substrate by docking to the catalytic residues that are important for AANAT activity. Myricetin significantly decreased the nocturnal serum melatonin levels in rats. In addition, the locomotor activity of rats treated with myricetin decreased during the nighttime and slightly increased throughout the day. These results suggest that myricetin could be used as a therapy to increase nighttime alertness by changing the circadian rhythm of serum melatonin and locomotor activity.

Detection of left atrial thrombus in patients with mitral stenosis and atrial fibrillation: retrospective comparison of two-phase computed tomography, transoesophageal echocardiography and surgical findings.

OBJECTIVE: This retrospective study aims to assess the accuracy of two-phase computed tomography (CT) and transoesophageal echocardiography (TEE) for the detection of left atrial (LA) thrombus in patients with mitral stenosis (MS) and atrial fibrillation (AF), by using intraoperative findings as the reference standard. METHODS: Preoperative two-phase CT and intraoperative TEE were performed in 106 patients with MS and AF. The ratio (LAA/AAL) of Hounsfield units (HU) in the LA appendage (LAA) to the ascending aorta (AA) was calculated on the late-phase CT image. RESULTS: LA echodense masses on TEE and LA filling defects on two-phase CT were observed in 29 and 39 patients, respectively. Thirty-five LA thrombi were identified at surgery in 27 patients. Compared with the intraoperative findings, per-patient sensitivity, specificity, positive and negative predictive values of two-phase CT were 100 %, 85 %, 69 % and 100 %, and those by using TEE were 93 %, 95 %, 86 % and 97 % in detecting LAA thrombus. After adopting the cut-off value of 0.5 for the LAA/AAL HU ratio, the specificity and positive predictive value of two-phase CT were increased to 96 % and 90 %, respectively. CONCLUSION: Two-phase CT with a cut-off value of LAA/AAL HU ratio of 0.5 provides high performance for the detection of LAA thrombus. KEY POINTS: • Accurate detection of left atrial appendage (LAA) thrombus is extremely important. • However artefacts from flow effects influence both CT and ultrasound findings. • Two-phase ECG-gated CT offers new insight into thrombus detection. • Analysis of aortic/atrial opacification helps differentiate LAA thrombus from artefact at CT.

Aortic Valve Dysfunction and Aortopathy Based on the Presence of Raphe in Patients with Bicuspid Aortic Valve Disease.

(1) Background: To identify the association between the presence or absence of a raphe and aortic valve dysfunction, as well as the presence of aortopathy in patients with a bicuspid aortic valve (BAV); (2) Methods: This retrospective study enrolled 312 participants (mean (SD) age, 52.7 (14.3) years; 227 men (72.8%)) with BAV. The BAVs were divided into those with the presence (raphe+) or absence (raphe-) of a raphe. Valvular function was classified as normal, aortic regurgitation (AR), or aortic stenosis (AS) using TTE. The pattern of BAV aortopathy was determined by the presence of dilatation at the sinus of Valsalva and the middle ascending aorta using CCT; (3) Results: BAVs with raphe+ had a higher prevalence of AR (148 (79.5%) vs. 48 (37.8%), p < 0.001), but a lower prevalence of AS (90 (48.6%) vs. 99 (78.0%), p < 0.001) compared with those with raphe-. The types of BAV aortopathy were significantly different (p = 0.021) according to those with BAV-raphe+ and BAV-raphe-; (4) Conclusions: The presence of a raphe was significantly associated with a higher prevalence of AR, but a lower prevalence of AS and combined dilatation of the aortic root and middle ascending aorta. The presence of a raphe was an independent determinant of AR.

Efficacy of Plant-Made Human Recombinant ACE2 against COVID-19 in a Golden Syrian Hamster Model.

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with SARS-CoV-2. Both hrACE2 and hrACE2-Fd inhibited SARS-CoV-2 by 50% at concentrations below the maximum plasma concentration, with EC50 of 5.8 µg/mL and 6.2 µg/mL, respectively. The hrACE2 and hrACE2-Fd injection groups showed a tendency for decreased viral titers in nasal turbinate tissues on day 3 after virus inoculation; however, this decrease was not detectable in lung tissues. Histopathological examination on day 9 after virus inoculation showed continued inflammation in the SARS-CoV-2 infection group, whereas decreased inflammation was observed in both the hrACE2 and hrACE2-Fd injection groups. No significant changes were observed at other time points. In conclusion, the potential therapeutic efficacy of plant-based proteins, hrACE2 and hrACE2-Fd, against COVID-19 was confirmed in a SARS-CoV-2-inoculated Golden Syrian hamster model. Further preclinical studies on primates and humans are necessary to obtain additional evidence and determine the effectiveness of these therapies.

A Plant-Derived Maternal Vaccine against Porcine Epidemic Diarrhea Protects Piglets through Maternally Derived Immunity.

Newborn piglets are susceptible to a highly contagious enteritis caused by the porcine epidemic diarrhea virus (PEDV), associated with high levels of mortality worldwide. There is pressing need for a rapid, safe, and cost-effective vaccine to safeguard pigs from getting infected by PEDV. PEDV belongs to the coronavirus family and is characterized by high levels of mutability. The primary goal of a PEDV vaccine is to provide immunity to newborn piglets through vaccination of sows. Plant-based vaccines are becoming more popular because they have low manufacturing costs, are easily scalable, have high thermostability, and a long shelf life. This is in contrast to conventional vaccines which include inactivated, live, and/or recombinant types that can be expensive and have limited ability to respond to rapidly mutating viruses. The binding of the virus to host cell receptors is primarily facilitated by the N-terminal subunit of the viral spike protein (S1), which also contains several epitopes that are recognized by virus-neutralizing antibodies. As a result, we generated a recombinant S1 protein using a plant-based vaccine platform. We found that the recombinant protein was highly glycosylated, comparable to the native viral antigen. Vaccination of pregnant sows at four and two weeks before farrowing led to the development of humoral immunity specific to S1 in the suckling piglets. In addition, we noted significant viral neutralization titers in both vaccinated sows and piglets. When challenged with PEDV, piglets born from vaccinated sows displayed less severe clinical symptoms and significantly lower mortality rates compared to piglets born from non-vaccinated sows.