Mice infected with Mycobacterium tuberculosis are resistant to acute disease caused by secondary infection with SARS-CoV-2.

Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 (CoV2) are the leading causes of death due to infectious disease. Although Mtb and CoV2 both cause serious and sometimes fatal respiratory infections, the effect of Mtb infection and its associated immune response on secondary infection with CoV2 is unknown. To address this question we applied two mouse models of COVID19, using mice which were chronically infected with Mtb. In both model systems, Mtb-infected mice were resistant to the pathological consequences of secondary CoV2 infection, and CoV2 infection did not affect Mtb burdens. Single cell RNA sequencing of coinfected and monoinfected lungs demonstrated the resistance of Mtb-infected mice is associated with expansion of T and B cell subsets upon viral challenge. Collectively, these data demonstrate that Mtb infection conditions the lung environment in a manner that is not conducive to CoV2 survival.

Donor plasmacytoid dendritic cells limit graft-versus-host disease through vasoactive intestinal polypeptide expression.

Vasoactive intestinal polypeptide (VIP), an anti-inflammatory neuropeptide with pleiotropic cardiovascular effects, induces differentiation of hematopoietic stem cells into regulatory dendritic cells that limit graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We have previously shown that donor plasmacytoid dendritic cells (pDCs) in bone marrow (BM) donor grafts limit the pathogenesis of GVHD. In this current study we show that murine and human pDCs express VIP, and that VIP-expressing pDCs limit T-cell activation and expansion using both in vivo and in vitro model systems. Using T cells or pDCs from transgenic luciferase+ donors in murine bone marrow transplantation (BMT), we show similar homing patterns of donor pDCs and T cells to the major sites for alloactivation of donor T cells: spleen and gut. Cotransplanting VIP-knockout (KO) pDCs with hematopoietic stem cells and T cells in major histocompatibility complex mismatched allogeneic BMT led to lower survival, higher GVHD scores, and more colon crypt cell apoptosis than transplanting wild-type pDCs. BMT recipients of VIP-KO pDCs had more T helper 1 polarized T cells, and higher plasma levels of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α than recipients of wild-type pDCs. T cells from VIP-KO pDC recipients had increasing levels of bhlhe40 transcripts during the first 2 weeks posttransplant, and higher levels of CyclophilinA/Ppia transcripts at day 15 compared with T cells from recipients of wild-type pDCs. Collectively, these data indicate paracrine VIP synthesis by donor pDCs limits pathogenic T-cell inflammation, supporting a novel mechanism by which donor immune cells regulate T-cell activation and GVHD in allogeneic BMT.

PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity.

Current limitations in using chimeric antigen receptor T(CART) cells to treat patients with hematological cancers include limited expansion and persistence in vivo that contribute to cancer relapse. Patients with chronic lymphocytic leukemia (CLL) have terminally differentiated T cells with an exhausted phenotype and experience low complete response rates after autologous CART therapy. Because PI3K inhibitor therapy is associated with the development of T-cell-mediated autoimmunity, we studied the effects of inhibiting the PI3Kδ and PI3Kγ isoforms during the manufacture of CART cells prepared from patients with CLL. Dual PI3Kδ/γ inhibition normalized CD4/CD8 ratios and maximized the number of CD8+ T-stem cell memory, naive, and central memory T-cells with dose-dependent decreases in expression of the TIM-3 exhaustion marker. CART cells manufactured with duvelisib (Duv-CART cells) showed significantly increased in vitro cytotoxicity against CD19+ CLL targets caused by increased frequencies of CD8+ CART cells. Duv-CART cells had increased expression of the mitochondrial fusion protein MFN2, with an associated increase in the relative content of mitochondria. Duv-CART cells exhibited increased SIRT1 and TCF1/7 expression, which correlated with epigenetic reprograming of Duv-CART cells toward stem-like properties. After transfer to NOG mice engrafted with a human CLL cell line, Duv-CART cells expressing either a CD28 or 41BB costimulatory domain demonstrated significantly increased in vivo expansion of CD8+ CART cells, faster elimination of CLL, and longer persistence. Duv-CART cells significantly enhanced survival of CLL-bearing mice compared with conventionally manufactured CART cells. In summary, exposure of CART to a PI3Kδ/γ inhibitor during manufacturing enriched the CART product for CD8+ CART cells with stem-like qualities and enhanced efficacy in eliminating CLL in vivo.

Insights into the Acidic Site in Manganese Oxide in Terms of the Sulfur and Water Tolerance of Low-Temperature NH3 Selective Catalytic Reduction.

A critical constraint impeding the utilization of Mn-based oxide catalysts in NH3 selective catalytic reduction (NH3-SCR) is their inadequate resistance to water and sulfur. This vulnerability primarily arises from the propensity of SO2 to bind to the acidic site in manganese oxide, resulting in the formation of metal sulfate and leading to the irreversible deactivation of the catalyst. Therefore, gaining a comprehensive understanding of the detrimental impact of SO2 on the acidic sites and elucidating the underlying mechanism of this toxicity are of paramount importance for the effective application of Mn-based catalysts in NH3-SCR. Herein, we strategically modulate the acidity of the manganese oxide catalyst surface through the incorporation of Ce and Nb. Comprehensive analyses, including thermogravimetry, NH3 temperature-programmed desorption, in situ diffused reflectance infrared Fourier transform spectroscopy, and density functional theory calculations, reveal that SO2 exhibits a propensity for adsorption at strongly acidic sites. This mechanistic understanding underscores the pivotal role of surface acidity in governing the sulfur resistance of manganese oxide.

Engineering of Pore Design and Oxygen Vacancy on High-Entropy Oxides by a Microenvironment Tailoring Strategy.

High-entropy oxides (HEOs) exhibit abundant structural diversity due to cationic and anionic sublattices with independence, rendering them superior in catalytic applications compared to monometallic oxides. Nevertheless, the conventional high-temperature calcination approach undermines the porosity and reduces the exposure of active sites (such as oxygen vacancies, OVs) in HEOs, leading to diminished catalytic efficiency. Herein, we fabricate a series of HEOs with a large surface area utilizing a microenvironment modulation strategy (m-NiMgCuZnCo: 86 m2/g, m-MnCuCoNiFe: 67 m2/g, and m-FeCrCoNiMn: 54 m2/g). The enhanced porosity in m-NiMgCuZnCo facilitates the presentation of numerous OVs, exhibiting an exceptional catalytic performance. This tactic creates inspiration for designing HEOs with rich porosity and active species with vast potential applications.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

Exploring publications in 3 major orthodontic journals: A comparative bibliometric analysis of two 10-year periods (2002-2011 and 2012-2021).

INTRODUCTION: This study aimed to perform a bibliometric analysis examining contributing countries and collaborative networks, authors and collaborative relationships, the performance of the institutions, and cocited journals and references in 3 major orthodontic journals (American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, and Angle Orthodontist) over two 10-year periods (2002-2011 and 2012-2021). METHODS: In this study, 4432 publications in the first decade and 4012 publications in the second decade were quantitatively analyzed and visualized using visualization software such as VOSviewer (Leiden University, Leiden, Netherlands), CiteSpace (Drexel University, Philadelphia, Pa), and Scimago Graphica (SCImago Lab, Spain). RESULTS: Institutions in the United States had the highest number of publications through the 2 decades, whereas Brazil, South Korea, and China achieved significant improvements in performance in the second decade compared with the first. Closer collaborative networks among scholars were revealed in the second decade. The cocitation analysis of the journals showed that highly cited journals included more professional orthodontic journals in the second decade than in the first decade. CONCLUSIONS: Bibliometric analysis of publications in 3 major orthodontic journals over two 10-year periods revealed a trend of diversification in countries and institutions participating in publishing, international collaborations, and collaboration networks among authors in the field of orthodontics during the 2 decades.

Bibliometric and visualized analysis of randomized controlled trials in orthodontics between 1991 and 2022.

INTRODUCTION: In many evidence-based approaches to orthodontic research, randomized controlled trials (RCTs) represent authoritative evidence to identify rational therapeutics. This study aimed to perform mappings of bibliometric networks on orthodontic RCTs and summarize visual characteristics between 1991 and 2022. METHODS: The articles were retrieved from the Web of Science Core Collection in October 2022 without an initial time limit. Only orthodontic RCTs were eligible. Some bibliometric tools (HistCite, VOSviewer, SCImago Graphica, and CiteSpace) were applied for visualized analysis. Data such as geography, productive institutions, hot articles, journals, authors, references, and keywords were extracted and summarized for analysis. RESULTS: A total of 1122 orthodontic RCTs were searched. A total of 3841 authors from 1157 institutions in 65 countries published orthodontic RCTs. The United States (149) was the most prolific country, and the University of Sao Paulo (35) was the most productive institution. The American Journal of Orthodontics and Dentofacial Orthopedics (206) was the most popular journal for scholars. The visualization results of keyword co-occurrence identified 5 clusters: (1) tooth movement and auxiliary measures, (2) appliances and oral health, (3) orthodontic discomfort and symptomatic therapy, (4) periodontal disease in orthodontics and health maintenance, and (5) retention and relapse. CONCLUSIONS: Over the past 31 years, publications and citations on orthodontic RCTs from the Web of Science Core Collection have increased notably across many countries, authors, and institutions. Recently, there has been a significant increase in the attention to orthodontic RCTs that focus on accelerating tooth movement.

Molecular epidemiology and transmission dynamics of multi-drug resistant tuberculosis strains using whole genome sequencing in the Amhara region, Ethiopia.

BACKGROUND: Drug resistant Mycobacterium tuberculosis prevention and care is a major challenge in Ethiopia. The World health organization has designated Ethiopia as one of the 30 high burden multi-drug resistant tuberculosis (MDR-TB) countries. There is limited information regarding genetic diversity and transmission dynamics of MDR-TB in Ethiopia. OBJECTIVE: To investigate the molecular epidemiology and transmission dynamics of MDR-TB strains using whole genome sequence (WGS) in the Amhara region. METHODS: Forty-five MDR-TB clinical isolates from Amhara region were collected between 2016 and 2018, and characterized using WGS and 24-loci Mycobacterium Interspersed Repetitive Units Variable Number of Tandem Repeats (MIRU-VNTR) typing. Clusters were defined based on the maximum distance of 12 single nucleotide polymorphisms (SNPs) or alleles as the upper threshold of genomic relatedness. Five or less SNPs or alleles distance or identical 24-loci VNTR typing is denoted as surrogate marker for recent transmission. RESULTS: Forty-one of the 45 isolates were analyzed by WGS and 44% (18/41) of the isolates were distributed into 4 clusters. Of the 41 MDR-TB isolates, 58.5% were classified as lineage 4, 36.5% lineage 3 and 5% lineage 1. Overall, TUR genotype (54%) was the predominant in MDR-TB strains. 41% (17/41) of the isolates were clustered into four WGS groups and the remaining isolates were unique strains. The predominant cluster (Cluster 1) was composed of nine isolates belonging to lineage 4 and of these, four isolates were in the recent transmission links. CONCLUSIONS: Majority of MDR-TB strain cluster and predominance of TUR lineage in the Amhara region give rise to concerns for possible ongoing transmission. Efforts to strengthen TB laboratory to advance diagnosis, intensified active case finding, and expanded contact tracing activities are needed in order to improve rapid diagnosis and initiate early treatment. This would lead to the interruption of the transmission chain and stop the spread of MDR-TB in the Amhara region.

Identification and transcriptome data analysis of ARF family genes in five Orchidaceae species.

The Orchidaceae is a large family of perennial herbs especially noted for the exceptional diversity of specialized flowers. Elucidating the genetic regulation of flowering and seed development of orchids is an important research goal with potential utility in orchid breeding programs. Auxin Response Factor (ARF) genes encode auxin-responsive transcription factors, which are involved in the regulation of diverse morphogenetic processes, including flowering and seed development. However, limited information on the ARF gene family in the Orchidaceae is available. In this study, 112 ARF genes were identified in the genomes of 5 orchid species (Apostasia shenzhenica, Dendrobium catenatum, Phalaenopsis aphrodite, Phalaenopsis equestris and Vanilla planifolia,). These genes were grouped into 7 subfamilies based on their phylogenetic relationships. Compared with the ARF family in model plants, such as Arabidopsis thaliana and Oryza sativa, one group of ARF genes involved in pollen wall synthesis has been lost during evolution of the Orchidaceae. This loss corresponds with absence of the exine in the pollinia. Through mining of the published genomic and transcriptomic data for the 5 orchid species: the ARF genes of subfamily 4 may play an important role in flower formation and plant growth, whereas those of subfamily 3 are potentially involved in pollen wall development. the study results provide novel insights into the genetic regulation of unique morphogenetic phenomena of orchids, which lay a foundation for further analysis of the regulatory mechanisms and functions of sexual reproduction-related genes in orchids.

Characteristics of and Deaths among 333 Persons with Tuberculosis and COVID-19 in Cross-Sectional Sample from 25 Jurisdictions, United States.

Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB-COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 [95% CI 0.8‒1.4]). Among TB-COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB-COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.

Tuning the Coordination Microenvironment of Central Fe Active Site to Boost Water Electrolysis and Oxygen Reduction Activity.

In heterogeneous catalysis, single-atom catalysts are the frontier and important prototypes for many reactions, and revealing the intrinsic structure-activity relationship is presently a critical task, but remains challenging. In this work, water electrolysis and oxygen reduction performances of FeXYi N3 -i (X, Y = B, C, O, P and S; i = 0, 1) moiety in Fe-porphyrin are studied by the first-principles calculations, aiming at unraveling how and why tuning the coordination microenvironment of the active metal atom can improve the activity. It can be concluded that breaking the coordination shell symmetry breaks the well-accepted standard scaling relationship, adjusts *O adsorption behavior and thus optimizes the oxygen evolution reaction (OER) activity, for example, to an extremely low overpotential of 0.17 V. In combination with the Fe atom spin configuration and ligand field theory, the dramatically improved OER activity can be well explained. In the present work, the significance of the coordination microenvironment of central metal atom in studies of electrocatalysis is highlighted.

Embedding Hierarchical Pores by Mechanochemistry in Carbonates with Superior Chemoselective Catalysis and Stability.

Hierarchical porosity of carbonates can facilitate their performance in massive applications as compared to their corresponding bulk samples. Traditional solution-based precipitation is typically utilized to fabricate porous carbonates. However, this tactic is generally employed under humid conditions, which demand soluble metal precursors, solvents, and extended dry periods. A salt-assisted mechanochemistry is exploited in contemporary work to settle the shortcomings. Enlighted by solid-state technology, this approach eliminates the utilization of solvents, and the process of ball milling can create pores in 5 min. A range of highly porous carbonates and their derivatives are acquired, with several materials surpassing recording surface areas (e.g., H-CaCO3: 108 m2/g, SrCO3: 125 m2/g, BaCO3: 172 m2/g, Pd/H-CaCO3 catalyst: 101 m2/g). The results display that Pd/H-CaCO3 shows superior catalytic efficiency in the synthesis of aniline (turnover frequency [TON] = 1.33 × 104/h-1, yield ≥ 99%, and recycle stability: 11 cycles) and dye degradation. Combining mechanochemistry and salt-assisted tactic provides a facile and efficient pathway for processing porous materials.

Clonal diversity of Staphylococcus aureus isolates in clinical specimens from selected health facilities in Ethiopia.

Staphylococcus aureus is among the top three causative agents of nosocomial infection in Ethiopia. The majority of studies in Ethiopia have focused on the epidemiology of S. aureus in hospital settings, with limited molecular genotyping results. Molecular characterization of S. aureus is essential for identification of strains, and contributes to the control and prevention of S. aureus infection. The aim of the current study was to determine the molecular epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates recovered from clinical specimens in Ethiopia. A total of 161 MSSA and 9 MRSA isolates were characterized using pulsed-field gel electrophoresis (PFGE) and staphylococcal protein A (spa) typing. Based on the PFGE analysis, MSSA isolates were grouped into eight pulso-types groups (from A to I), while MRSA isolates clustered into three (A, B and C) pulso-types with more than 80% similarity. The spa typing analysis showed diversity of S. aureus with 56 distinct spa types. Spa type t355 was most prevalent (56/170, 32.9%), while eleven new spa types were detected including t20038, t20039, and t20042. The identified spa types were clustered into 15 spa-clonal complexes (spa-CCs) using BURP analysis; novel/unknown spa types were further subjected to MLST analysis. The majority of isolates belonged to spa-CC 152 (62/170, 36.4%), followed by spa-CC 121 (19/170, 11.2%), and spa-CC 005 (18 /170, 10.6%). Of the nine MRSA isolates, 2 (22.2%) were spa-CC 239 with staphylococcal cassette chromosome (SCC)mec III. These findings highlight the diversity of S. aureus strains in Ethiopia, as well as the presence of potentially epidemic strains circulating in the country necessitating further characterization of S. aureus for antimicrobial resistance detection and infection prevention purposes.

Screening for Latent Tuberculosis Infection in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective: To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection: English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures: Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results: A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance: No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

Spontaneous Valley Polarization Caused by Crystalline Symmetry Breaking in Nonmagnetic LaOMX2 Monolayers.

In order to achieve valley polarization, breaking the time-reversal symmetry in two-dimensional hexagonal lattices with inversion asymmetry is the heart of current valleytronic research, which, however, has caused studies to stagnate due to the inevitable drawbacks. In this work, we go beyond the conventional paradigm and demonstrate the novel valley physics caused by lowering the crystalline symmetry instead of breaking the time-reversal symmetry. In particular, we translate our concept into concrete nonmagnetic LaOMX2 monolayers with a tetragonal lattice, confirming that a spontaneous structure distortion can cause the long-sought, considerably large valley polarization. In detail, the physics of valley-orbital coupling, valley-orbital-layer coupling, valley-contrasting linear dichroism, and interlayer exciton valleytronics are discussed.

Evaluation of Left Ventricular Mass in Different Cardiac Geometry Using Three-Dimensional Contrast-Enhanced Echocardiography.

A total of 69 patients were enrolled in the study, including 23 patients with hypertrophic cardiomyopathy (HCM), 26 patients with Left Ventricle (LV) enlargement comprising 16 dilated cardiomyopathy (DCM) patients and 10 ischemic cardiomyopathy (ICM) patients, and 20 control subjects. All patients underwent 2DE, contrast-enhanced 2DE (Contrast-2DE), 3DE, Contrast-3DE, and single photon emission computed tomography (SPECT) examinations. The 2DE-AL and 3DE methods measured the left ventricular mass (LVM). The results were compared with those measured by SPECT. The measured LVM of the 69 patients was systematically overestimated by 2DE-AL (177.4 ± 56.2 g), Contrast-2DE-AL (174.5 ± 55.5 g), 3DE (167.3 ± 59.2 g), and Contrast-3DE (154.2 ± 46.7 g) when compared with SPECT (148.5 ± 52.4 g) (P < 0.05), while Contrast-3DE provided the best agreement with SPECT in LVM measurement (r = 0.898, P < 0.001) and had the smallest deviation (5.7 ± 23.1 g). 3DE overestimated LVM more compared to Contrast-3DE in LV hypertrophy group (165.5 ± 37.9 g versus 153.5 ± 27.6 g, P = 0.003) and LV enlargement group (204.5 ± 69.3 g versus 183.5 ± 53.5 g, P = 0.006). For 2DE methods, there was no significant difference between the LVM obtained with or without contrast enhancement in control group (132.3 ± 23.6 g versus 128.4 ± 23.3 g), LV hypertrophy group (177.7 ± 38.6 versus 178.3 ± 30.9 g, P = 0.889), and LV enlargement group (211.9 ± 63.2 g versus 206.5 ± 66.0 g, P = 0.386). The difference between LVM measured by 2DE-AL and SPECT was the greatest (27.9 ± 34.0 g), especially in LV hypertrophy group and LV enlargement group (LV hypertrophy group 39.7 ± 26.0 g; LV enlargement group 24.2 ± 42.8 g). To conclude, Contrast-3DE and SPECT show greater consistency in LVM measurement, especially in cardiomyopathy, when compared with 2DE. Administering contrast can effectively reduce the overestimation of LVM by non-contrast DE.

Association Between Vancomycin AUC and Clinical Failure in Patients with Streptococcal Bacteremia.

Background: Monitoring of vancomycin using the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is now preferred for serious methicillin-resistant Staphylococcus aureus infections. Vancomycin AUC/MIC monitoring is being investigated but is not yet well elucidated with other bacterial pathogens. Methods: A retrospective cross-sectional study was conducted assessing patients with streptococcal bacteremia treated with vancomycin definitive therapy. AUC was calculated using a Bayesian approach, and classification and regression tree analysis was used to identify a vancomycin AUC threshold predictive of clinical failure. Results: Eleven patients had a vancomycin AUC < 329 of which 8 (73%) experienced clinical failure, while 35 patients had a vancomycin AUC ≥ 329 of which 12 (34%) experienced clinical failure (P = .04). Hospital length of stay was longer in the AUC ≥ 329 group (15 vs 8 days, P = .05), whereas time to bacteremia clearance (29 [22-45] vs 25 [20-29] hours, P = .15) and toxicity incidence (13% vs 4%, P = 1) were similar between groups. Conclusions: This study identified a VAN AUC threshold of <329 to be predictive of clinical failure in patients with streptococcal bacteremia which should be interpreted as hypothesis-generating. Studies evaluating VAN AUC-based monitoring for streptococcal bloodstream infections along with other infection types are needed before implementation into clinical practice can be recommended.

Novel Automation of an Enzyme-Linked Immunosorbent Spot Assay Testing Method: Comparable Diagnostic Performance of the T-SPOT.TB Test Using Manual Density Gradient Cell Isolation versus Automated Positive Selection with the T-Cell Select Kit.

The diagnosis of latent tuberculosis (TB) infection (LTBI) is critical to improve TB treatment and control, and the T-SPOT.TB test is a commercial enzyme-linked immunosorbent spot assay used for this purpose. The objective of the study was to increase automation and extend the time between blood collection and processing for the T-SPOT.TB test from 0 to 8 h to 0 to 54 h. The previous maximum time between blood collection and processing for the T-SPOT.TB test is 32 h using T-Cell Xtend. For this, we compared the T-SPOT.TB test using manual peripheral blood mononuclear cell (PBMC) isolation by density gradient separation at 0 to 8 h (reference method, control arm) to an automated PBMC isolation method using magnetic beads (T-Cell Select kit) at 0 to 55 h postcollection. A total of 620 subjects were enrolled from 4 study sites, and blood samples were collected from each volunteer, comprising 1,850 paired samples in total. Overall agreement between both methods was 96.8% (confidence interval [CI], 95.9 to 97.6%), with 95.8% (CI, 93.5 to 97.5%) positive and 97.1% negative agreement (CI, 96.1 to 97.9%). In summary, there was a strong overall agreement between the automated and manual T-SPOT.TB test processing methods. The results suggest that the T-SPOT.TB test can be processed using automated positive selection with magnetic beads using T-Cell Select to decrease hands-on time. Also, this cell isolation method allowed for the time between blood collection and processing to range from 0 to 55 h. Additional studies in larger and diverse patient populations including immunocompromised and pediatric patients are needed.

Green and Large-Scale Preparation of Chiral Metal-Organic Frameworks via Mechanochemistry.

It is a significant challenge to construct chiral metal-organic frameworks (CMOFs) by developing a facile and green preparation strategy. In this work, CMOFs were first synthesized via a mechanochemical process by combining a truncated mixed ligand strategy and defect engineering theory. The simple, green, and rapid construction strategy could solvent-freely harvest gram-scale CMOFs with a hierarchical micro/mesoporous structure. The as-synthesized CMOFs were evaluated by Aldol asymmetric catalysis and exhibited excellent catalytic performance (conversion was up to 97.1%, the ee value was 44.3%, and the activity was still good after 5 cycles).