A simple and sensitive test for Candida auris colonization, surveillance, and infection control suitable for near patient use.

Candida auris is a multidrug-resistant fungal pathogen with a propensity to colonize humans and persist on environmental surfaces. C. auris invasive fungal disease is being increasingly identified in acute and long-term care settings. We have developed a prototype cartridge-based C. auris surveillance assay (CaurisSurV cartridge; "research use only") that includes integrated sample processing and nucleic acid amplification to detect C. auris from surveillance skin swabs in the GeneXpert instrument and is designed for point-of-care use. The assay limit of detection (LoD) in the skin swab matrix was 10.5 and 14.8 CFU/mL for non-aggregative (AR0388) and aggregative (AR0382) strains of C. auris, respectively. All five known clades of C. auris were detected at 2-3-5× (31.5-52.5 CFU/mL) the LoD. The assay was validated using a total of 85 clinical swab samples banked at two different institutions (University of California Los Angeles, CA and Wadsworth Center, NY). Compared to culture, sensitivity was 96.8% (30/31) and 100% (10/10) in the UCLA and Wadsworth cohorts, respectively, providing a combined sensitivity of 97.5% (40/41), and compared to PCR, the combined sensitivity was 92% (46/50). Specificity was 100% with both clinical (C. auris negative matrix, N = 31) and analytical (non-C. auris strains, N = 32) samples. An additional blinded study with N = 60 samples from Wadsworth Center, NY yielded 97% (29/30) sensitivity and 100% (28/28) specificity. We have developed a completely integrated, sensitive, specific, and 58-min prototype test, which can be used for routine surveillance of C. auris and might help prevent colonization and outbreaks in acute and chronic healthcare settings. IMPORTANCE: This study has the potential to offer a better solution to healthcare providers at hospitals and long-term care facilities in their ongoing efforts for effective and timely control of Candida auris infection and hence quicker response for any potential future outbreaks.

PERSISTENT SUBRETINAL FLUID AFTER VITRECTOMY FOR MACULAR HOLE-ASSOCIATED RETINAL DETACHMENT.

PURPOSE: To evaluate the incidence, associated factors, and outcome of persistent subretinal fluid (SRF) after vitrectomy for macular hole-associated retinal detachment (MHRD). METHODS: A total of 158 eyes from 156 patients with MHRD who achieved macular hole closure after primary vitrectomy were included in the analysis; persistent SRF was defined as the presence of SRF for more than 1 month after first surgery. Preoperative and postoperative parameters were analyzed for their relationship with SRF development. RESULTS: Persistent SRF was observed in 19 eyes (12.0% of 158) postoperatively. Seven eyes (36.8% of 19) with persistent SRF eventually displayed complete absorption during follow-up. Univariate analysis revealed that eyes with persistent SRF were statistically associated with internal limiting membrane inverted flap, duration of symptoms, tamponade (perfluoropropane/silicone oil: 14/5 vs. 35/104, P < 0.001), and MHRD subtype (Type 1/Type 2/Type 3: 15/4/0 vs. 60/40/39, P = 0.003). In multivariate analysis, only internal limiting membrane inverted flap (odds ratio, 15.778, 95% confidence interval, 3.170-78.523; P = 0.001) was positively associated with persistent SRF. There were no significant differences in best-corrected visual acuity improvement ( P = 0.425) between the SRF involved foveal and without involved foveal groups and no significant differences between the SRF complete absorption and incomplete absorption groups. CONCLUSION: Absorption of persistent SRF may be more difficult in MHRD eyes than in ordinary rhegmatogenous retinal detachment eyes. The internal limiting membrane inverted flap in MHRD was associated with a greater likelihood of persistent SRF. The location and incomplete absorption of persistent SRF did not seem to be associated with the final visual outcome.

Development and Validation of TaqMan Chemistry Probe-Based Rapid Assay for the Detection of Echinocandin-Resistance in Candida auris.

Candida auris is a multidrug-resistant yeast pathogen causing outbreaks in health care facilities worldwide, and the emergence of echinocandin-resistant C. auris is a concern. Currently used Clinical and Laboratory Standards Institute (CLSI) and commercial antifungal susceptibility tests (AFST) are phenotype-based, slow, and not scalable, limiting their effectiveness in the surveillance of echinocandin-resistant C. auris. The urgent need for accurate and rapid methods of assessment of echinocandin resistance cannot be overstated, as this class of antifungal drugs is preferred for patient management. We report the development and validation of a TaqMan chemistry probe-based fluorescence melt curve analysis (FMCA) following asymmetric polymerase chain reaction (PCR) to assess mutations within the hot spot one (HS1) region of FKS1, the gene responsible for encoding 1,3-ß-d-glucan synthase that is a target for echinocandins. The assay correctly identified F635C, F635Y, F635del, F635S, S639F or S639Y, S639P, and D642H/R645T mutations. Of these mutations, F635S and D642H/R645T were not involved in echinocandin resistance, while the rest were, as confirmed by AFST. Of 31 clinical cases, the predominant mutation conferring echinocandin resistance was S639F/Y (20 cases) followed by S639P (4 cases), F635del (4 cases), F635Y (2 cases), and F635C (1 case). The FMCA assay was highly specific and did not cross-react with closely and distantly related Candida and other yeast and mold species. Structural modeling of the Fks1 protein, its mutants, and docked conformations of three echinocandin drugs suggest a plausible Fks1 binding orientation for echinocandins. These findings lay the groundwork for future evaluations of additional FKS1 mutations and their impact on the development of drug resistance. The TaqMan chemistry probe-based FMCA would allow rapid, high throughput, and accurate detection of FKS1 mutations conferring echinocandin resistance in C. auris.

Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents.

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.

Utility of CHROMagar™ Candida Plus for presumptive identification of Candida auris from surveillance samples.

Candida auris is a nosocomial fungal pathogen of prime importance due to its global emergence and rapid spread in healthcare facilities worldwide. One important concern is that routine, conventional methods fail to identify C. auris. While molecular and protein-based assays accurately detect/identify C. auris, these methods are time-consuming, expensive, and require expertise. Therefore, the objective of the present study was to assess the potential use of a novel chromogenic medium, CHROMagar™ Candida Plus, as an economical alternative to expensive and laborious diagnostic tests. We compared CHROMagar™ Candida Plus with the standard enrichment (salt Sabouraud Dulcitol broth) medium to test the recovery efficiency of C. auris from surveillance samples. We also tested CHROMagar™ Candida Plus for its ability to distinguish C. auris from other yeast species. One hundred surveillance samples were cultured on CHROMagar™ Candida Plus and Dulcitol broth and incubated at 37 °C and 40 °C, respectively. Additionally, 32 Candida and yeast species were cultured on CHROMagar™ Candida Plus at 37 °C for three days to rule out any close resemblance to C. auris. Of 100 surveillance samples tested, 69 yielded presumptive positive C. auris exhibiting creamy pink colonies with a blue halo on CHROMagar™ Candida Plus within three days of incubation, and MALDI-TOF MS confirmed all by day 4. On the other hand, 69 of 100 surveillance samples yielded turbidity in Dulcitol broth by days 3-14 with final MALDI identification by days 5 to 17. Both media failed to identify one sample each, resulting in assay sensitivity and specificity of 99% and 97%, respectively. Of Candida and yeast species tested, 75-80% of C. metapsilosis and C. orthospilosis were misidentified as C. auris. However, previous studies indicated that these species are rarely detected in surveillance screening of C. auris. Naganishia diffluens also resembled C. auris, although it required different temperature growth (30 °C). In conclusion, CHROMagar™ Candida Plus provides rapid presumptive identification of C. auris. It would be another valuable tool in surveillance efforts to control the spread of C. auris in healthcare.

Development of a Duplex Real-Time PCR Assay for the Differentiation of Blastomyces dermatitidis and Blastomyces gilchristii and a Retrospective Analysis of Culture and Primary Specimens from Blastomycosis Cases from New York (2005 to 2019).

Blastomycosis due to Blastomyces dermatitidis and Blastomyces gilchristii is a significant cause of respiratory mycoses in North America with occasional reported outbreaks. We developed a highly sensitive, specific, and reproducible TaqMan duplex real-time PCR assay for the differentiation of B. dermatitidis and B. gilchristii The new assay permitted retrospective analysis of Blastomyces cultures (2005 to 2019) and primary clinical specimens from blastomycosis cases (2013 to 2019) from New York patients. We identified B. dermatitidis as the predominant pathogen in 38 cases of blastomycosis, while B. gilchristii was a minor pathogen involved in five cases; these findings expand understanding of blastomycosis in New York. The duplex real-time PCR assay could be implemented in reference and public health laboratories to further understand the ecology and epidemiology of blastomycosis due to B. dermatitidis and B. gilchristii.

Salt-induced inhibition of rice seminal root growth is mediated by ethylene-jasmonate interaction.

The phytohormones ethylene and jasmonate play important roles in the adaptation of rice plants to salt stress. However, the molecular interactions between ethylene and jasmonate on rice seminal root growth under salt stress are unknown. In this study, the effects of NaCl on the homeostasis of ethylene and jasmonate, and on rice seminal root growth were investigated. Our results indicate that NaCl treatment promotes ethylene biosynthesis by up-regulating the expression of ethylene biosynthesis genes, whereas NaCl-induced ethylene does not inhibit rice seminal root growth directly, but rather indirectly, by promoting jasmonate biosynthesis. NaCl treatment also promotes jasmonate biosynthesis through an ethylene-independent pathway. Moreover, NaCl-induced jasmonate reduces meristem cell number and cell division activity via down-regulated expression of Oryza sativa PLETHORA (OsPLT) and cell division-related genes, respectively. Additionally, NaCl-induced jasmonate inhibits seminal root cell elongation by down-regulating the expression of cell elongation-related genes. Overall, salt stress promotes jasmonate biosynthesis through ethylene-dependent and -independent pathways in rice seminal roots, and jasmonate inhibits rice seminal root growth by inhibiting root meristem cell proliferation and root cell elongation.

Molecular and Genetic Aspects of Grain Number Determination in Rice (Oryza sativa L.).

Rice grain yield is a complex trait determined by three components: panicle number, grain number per panicle (GNPP) and grain weight. GNPP is the major contributor to grain yield and is crucial for its improvement. GNPP is determined by a series of physiological and biochemical steps, including inflorescence development, formation of rachis branches such as primary rachis branches and secondary rachis branches, and spikelet specialisation (lateral and terminal spikelets). The molecular genetic basis of GNPP determination is complex, and it is regulated by numerous interlinked genes. In this review, panicle development and the determination of GNPP is described briefly, and GNPP-related genes that influence its determination are categorised according to their regulatory mechanisms. We introduce genes related to rachis branch development and their regulation of GNPP, genes related to phase transition (from rachis branch meristem to spikelet meristem) and their regulation of GNPP, and genes related to spikelet specialisation and their regulation of GNPP. In addition, we describe other GNPP-related genes and their regulation of GNPP. Research on GNPP determination suggests that it is possible to cultivate rice varieties with higher grain yield by modifying GNPP-related genes.

In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak.

An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are panresistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug fosmanogepix is currently in phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90, 0.03 mg/liter; range, 0.004 to 0.06 mg/liter). The local epidemiological cutoff value (ECV) for MGX indicated all C. auris isolates were within the population of wild-type (WT) strains; 0.06 mg/liter defines the upper limit of wild type (UL-WT). MGX was 8- to 32-fold more active than the echinocandins, 16- to 64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators' MIC50, MIC90, or geometric mean (GM) values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris panresistant isolates was 0.008 to 0.015 mg/liter, and the median and mode MIC values were 0.015 mg/liter, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018: Impact and Lessons Learned.

Candida auris is a multidrug-resistant yeast which has emerged in health care facilities worldwide; however, little is known about identification methods, patient colonization, environmental survival, spread, and drug resistance. Colonization on both biotic (patients) and abiotic (health care objects) surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in New York (NY) from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/nonselective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of the internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal gene for C. auris genotyping. Results included (a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates as well as identification of 277 clinical cases and 350 colonized cases from 151 health care facilities, including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, (b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, (c) demonstration of relatively heavier colonization of C. auris in nares than in the axilla/groin, and (d) predominance of the South Asia clade I with intrinsic resistance to fluconazole and elevated MIC to voriconazole (81%), amphotericin B (61%), flucytosine (5FC) (3%), and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

3D self-gated cardiac cine imaging at 3 Tesla using stack-of-stars bSSFP with tiny golden angles and compressed sensing.

PURPOSE: To develop and evaluate an accelerated 3D self-gated cardiac cine imaging technique at 3 Tesla without the use of external electrocardiogram triggering or respiratory gating. METHODS: A 3D stack-of-stars balanced steady-state free precession sequence with a tiny golden angle sampling scheme was developed to reduced eddy current effect-related artefacts at 3 Tesla. Respiratory and cardiac motion were derived from a central 5-point self-gating signal extraction approach. The data acquired around the end-expiration phases were then sorted into individual cardiac bins and used for reconstruction with compressed sensing. To evaluate the performance of the proposed method, image quality (1: the best; 4: the worst) was quantitatively compared using both the proposed method and the conventional 3D golden-angle self-gated method. Linear regression and Bland-Altman analysis were used to assess the functional measurements agreement between the proposed method and the routine 2D breath-hold multi-slice technique. RESULTS: Compared to the conventional 3D golden-angle self-gated method, the proposed method yielded images with much less streaking artifact and higher myocardium edge sharpness (0.50 ± 0.06 vs. 0.45 ± 0.05, P = 0.004). The proposed method provided an inferior image quality score to the routine 2D technique (2.13 ± 0.35 vs. 1.38 ± 0.52, P = 0.063) but a superior one to the conventional self-gated method (2.13 ± 0.35 vs. 3.13 ± 0.64, P = 0.031). Left ventricular functional measurements between the proposed method and routine 2D technique were all well in agreement. CONCLUSION: This study presents a novel self-gating approach to realize rapid 3D cardiac cine imaging at 3 Tesla.

Short T2 imaging using a 3D double adiabatic inversion recovery prepared ultrashort echo time cones (3D DIR-UTE-Cones) sequence.

PURPOSE: To investigate high contrast imaging of short T2 tissues with a three-dimensional double adiabatic inversion recovery prepared ultrashort echo time Cones (3D DIR-UTE-Cones) sequence. METHODS: The sequence used two sequential adiabatic inversion pulses to suppress signals from long T2 tissues, followed by multispoke UTE acquisition to detect signals from short T2 tissues. The two adiabatic inversion pulses are identical with a center frequency located at the water peak, but the spectral width is broad enough to cover both water and fat frequencies. The feasibility of this technique was demonstrated through numerical simulation and phantom studies. Finally, DIR-UTE-Cones was applied to three healthy volunteers to image cortical bone, patellar tendon, and Achilles tendon. T2* was also measured via single-component exponential fitting. RESULTS: Numerical simulation suggests that the DIR technique provides perfect nulling of muscle and fat as well as efficient suppression of other long T2 tissues with T1 values between fat and water or those above water. Excellent image contrast can be achieved with DIR-UTE-Cones for the short T2 tissues, with fitted T2* values of 0.28-0.38 ms for cortical bone, 0.56 ± 0.07 ms for the patella tendon, and 0.45 ± 0.06 ms for the Achilles tendon, respectively. CONCLUSION: The 3D DIR-UTE-Cones sequence provides robust suppression of long T2 tissues and allows selective imaging as well as T2* measurement of short T2 tissues such as cortical bone, patellar tendon, and the Achilles tendon. Magn Reson Med 79:2555-2563, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Yet more evidence that myelin protons can be directly imaged with UTE sequences on a clinical 3T scanner: Bicomponent T2* analysis of native and deuterated ovine brain specimens.

PURPOSE: UTE sequences with a minimal nominal TE of 8 µs have shown promise for direct imaging of myelin protons (T2 , < 1 ms). However, there is still debate about the efficiency of 2D slice-selective UTE sequences in exciting myelin protons because the half excitation pulses used in these sequences have a relatively long duration (e.g., 0.3-0.6 ms). Here, we compared UTE and inversion-recovery (IR) UTE sequences used with either hard or half excitation pulses (durations 32 µs or 472 µs, respectively) for imaging myelin in native and deuterated ovine brain at 3T. METHODS: Freshly frozen ovine brains were dissected into ∼2 mm-thick pure white matter and ∼3 to 8 mm-thick cerebral hemisphere specimens, which were imaged before and/or after different immersion time in deuterium oxide. RESULTS: Bicomponent T2* analysis of UTE signals obtained with hard excitation pulses detected an ultrashort T2 component (STC) fraction (fS ) of 0% to 10% in native specimens, and up to ∼86% in heavily deuterated specimens. fS values were significantly affected by the TIs used in IR-UTE sequences with either hard or half excitation pulses in native specimens but not in heavily deuterated specimens. The STC T2* was in the range of 150 to 400 µs in all UTE and IR-UTE measurements obtained with either hard or half excitation pulses. CONCLUSION: Our results further support myelin protons as the major source of the ultrashort T2* signals seen on IR-UTE images and demonstrate the potential of IR-UTE sequences with half excitation pulses for directly imaging myelin using clinical scanners. Magn Reson Med 80:538-547, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Accurate T1 mapping of short T2 tissues using a three-dimensional ultrashort echo time cones actual flip angle imaging-variable repetition time (3D UTE-Cones AFI-VTR) method.

PURPOSE: To develop an accurate T1 measurement method for short T2 tissues using a combination of a 3-dimensional ultrashort echo time cones actual flip angle imaging technique and a variable repetition time technique (3D UTE-Cones AFI-VTR) on a clinical 3T scanner. METHODS: First, the longitudinal magnetization mapping function of the excitation pulse was obtained with the 3D UTE-Cones AFI method, which provided information about excitation efficiency and B1 inhomogeneity. Then, the derived mapping function was substituted into the VTR fitting to generate accurate T1 maps. Numerical simulation and phantom studies were carried out to compare the AFI-VTR method with a B1 -uncorrected VTR method, a B1 -uncorrected variable flip angle (VFA) method, and a B1 -corrected VFA method. Finally, the 3D UTE-Cones AFI-VTR method was applied to bovine bone samples (N = 6) and healthy volunteers (N = 3) to quantify the T1 of cortical bone. RESULTS: Numerical simulation and phantom studies showed that the 3D UTE-Cones AFI-VTR technique provides more accurate measurement of the T1 of short T2 tissues than the B1 -uncorrected VTR and VFA methods or the B1 -corrected VFA method. The proposed 3D UTE-Cones AFI-VTR method showed a mean T1 of 240 ± 25 ms for bovine cortical bone and 218 ± 10 ms for the tibial midshaft of human volunteers, respectively, at 3 T. CONCLUSION: The 3D UTE-Cones AFI-VTR method can provide accurate T1 measurements of short T2 tissues such as cortical bone. Magn Reson Med 80:598-608, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Rotator cuff tendon assessment using magic-angle insensitive 3D ultrashort echo time cones magnetization transfer (UTE-Cones-MT) imaging and modeling with histological correlation.

BACKGROUND: Rotator cuff tendons (RCTs) are challenging to image due to the "magic angle effect" and their short T2 . PURPOSE: To assess the degree of magic angle sensitivity of human RCTs and to utilize a 3D ultrashort echo time Cones sequence with magnetization transfer preparation (UTE-Cones-MT) and two-pool quantitative MT modeling with histological correlation. We hypothesized that MT parameters would be less sensitive to the magic angle compared with conventional T2 measurements. STUDY TYPE: Prospective imaging pathologic correlation. SPECIMEN: Twenty cadaveric rotator cuff tendons were imaged at five sample orientations ranging from 0-90° relative to the B0 field. FIELD STRENGTH/SEQUENCE: 3T/3D UTE-Cones-MT and Carr-Purcell-Meiboom-Gill (CPMG). ASSESSMENT: Two-pool quantitative MT modeling parameters and T2 values were calculated in regions of interest drawn by a medical physicist. Histopathological analysis was performed and mild and severe tendinopathy groups were assigned by a histopathologist and histotechnician. STATISTICAL TESTS: Coefficients of variations (CVs) were calculated for measures between the different orientations and group means were compared for each measure. RESULTS: CVs of T2 and macromolecular fractions between orientations were 26.14 ± 16.82% and 6.18 ± 2.77% (mean ± SD), respectively. T2 measurements at 0°, 27°, 70°, and 90° showed significant differences between the two histological groups (P = 0.004, 0.008, 0.003, and 0.015, respectively), but not at 55° (P = 0.611). Mean T2 value ranges between orientations for the mild and severe tendinopathy groups were 15.27-30.32 msec and 20.81-35.85 msec, respectively, showing overlap despite statistically significant differences (P = 0.003). Macromolecular fractions at all angles showed significant differences between the two groups (P < 0.0001). Mean fraction ranges between orientations for the mild and severe tendinopathy groups were 14.32-17.17% and 10.00-13.75% respectively (P < 0.0001) with no overlap. DATA CONCLUSION: Compared with T2 , macromolecular fraction obtained with the 3D UTE-Cones-MT technique is resistant to the magic angle effect and is more sensitive to RCT degeneration. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

Supraoptimal Cytokinin Content Inhibits Rice Seminal Root Growth by Reducing Root Meristem Size and Cell Length via Increased Ethylene Content.

Cytokinins (CKs), a class of phytohormone, regulate root growth in a dose-dependent manner. A certain threshold content of CK is required for rapid root growth, but supraoptimal CK content inhibits root growth, and the mechanism of this inhibition remains unclear in rice. In this study, treatments of lovastatin (an inhibitor of CK biosynthesis) and kinetin (KT; a synthetic CK) were found to inhibit rice seminal root growth in a dose-dependent manner, suggesting that endogenous CK content is optimal for rapid growth of the seminal root in rice. KT treatment strongly increased ethylene level by upregulating the transcription of ethylene biosynthesis genes. Ethylene produced in response to exogenous KT inhibited rice seminal root growth by reducing meristem size via upregulation of OsIAA3 transcription and reduced cell length by downregulating transcription of cell elongation-related genes. Moreover, the effects of KT treatment on rice seminal root growth, root meristem size and cell length were rescued by treatment with aminoethoxyvinylglycine (an inhibitor of ethylene biosynthesis), which restored ethylene level and transcription levels of OsIAA3 and cell elongation-related genes. Supraoptimal CK content increases ethylene level by promoting ethylene biosynthesis, which in turn inhibits rice seminal root growth by reducing root meristem size and cell length.

Dicliptera chinensis-derived polysaccharide enhanced the growth activity of submandibular gland cells in vitro after radiotherapy.

Objective: Radiotherapy for head and neck can damage the salivary gland cells, which can easily result in xerostomia. No effective treatment for radiation-induced salivary gland dysfunction currently exists. Thus, we aimed to study the protective effect of Dicliptera chinensis polysaccharides (DCP) on the prevention of submandibular gland (SMG) cell damage caused by radiotherapy in Sprague-Dawley rats. Design: Mechanical enzyme digestion was used to extract primary rat SMG cells. A radiation injury model was established by treating these cells with a dose of 8 Gy, followed by intervention using different DCP concentrations. The cell counting kit 8 assay was used to determine the inhibition rate of SMG cells in each group. The rates of apoptosis and cell cycle progression were detected using flow cytometry. Expression of the Mre11/Rad50/Nbs1 complex (MRN) was detected using western blotting. Results: DCP increased the proliferation of SMG cells after irradiation, and cell growth activity positively correlated with polysaccharide concentration. Flow cytometry analysis of SMG cell apoptosis revealed that DCP markedly reduced the total apoptosis rate after irradiation, especially the early apoptosis rate. Cell cycle results suggested that DCP reduced the number of cells in the S and G2 phases after irradiation and alleviated the S and G2 blocks. Western blot results indicated that the expression of Mre11, Rad50, and Nbs1 decreased in the radiation-injured group, whereas their expression increased after DCP treatment. Conclusions: DCP can protect the rat SMG cells after radiation and be used as a protective agent against salivary gland cell damage caused by radiotherapy.

Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae.

Importance: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission. Objective: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing. Design, Setting, and Participants: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers. Main Outcome and Measure: Improvement or resolution at the last follow-up assessment. Results: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 µg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates. Conclusion and Relevance: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

Modeling emotional contagion in the COVID-19 pandemic: a complex network approach.

During public health crises, the investigation into the modes of public emotional contagion assumes paramount theoretical importance and has significant implications for refining epidemic strategies. Prior research predominantly emphasized the antecedents and aftermath of emotions, especially those of a negative nature. The interplay between positive and negative emotions, as well as their role in the propagation of emotional contagion, remains largely unexplored. In response to this gap, an emotional contagion model was developed, built upon the foundational model and enriched from a complex network standpoint by integrating a degradation rate index. Stability analyses of this model were subsequently conducted. Drawing inspiration from topological structural features, an enhanced model was introduced, anchored in complex network principles. This enhanced model was then experimentally assessed using Watts-Strogatz's small-world network, Barabási-Albert's scale-free network, and Sina Weibo network frameworks. Results revealed that the rate of infection predominantly dictates the velocity of emotional contagion. The incitement rate and purification rate determine the overarching direction of emotional contagion, whereas the degradation rate modulates the waning pace of emotions during intermediate and later stages. Furthermore, the immunity rate was observed to influence the proportion of each state at equilibrium. It was discerned that a greater number of initial emotional disseminators, combined with a larger initial contagion node degree, can amplify the emotion contagion rate across the social network, thus augmenting both the peak and overall influence of the contagion.