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Primary Objective: Undetected cognitive impairment resulting from Traumatic Brain Injuries (TBIs), particularly the 75–95% classified as mild (mTBI), poses a significant public health challenge as untreated symptoms, can persist and cause lasting disability. These cognitive deficits are often missed by standard screening tests, creating a need for alternative cognitive screening tools. The Clock Drawing Test (CDT), a popular, brief cognitive screening instrument, was used to evaluate cognition in persons with TBI. Design: The effectiveness of the CDT was assessed on its own and in tandem with a validated computerised screening battery, including the Stroop Test, Symbol Digit Modalities Test (SDMT), and Paced Visual Serial Addition Test 2-second trials (PVSAT-2). Methods and Procedures: The clock drawing component of the Montreal Cognitive Assessment (MoCA) of 223 subjects attending an outpatient TBI clinic was scored using two different methods. Main Outcomes and Results: The CDT screened for cognitive impairment most effectively when scored using the Clock Drawing Interpretation Scale (CDIS). Cognitive impairment was detected in 19.4% of the elusive cohort of persons with mTBI. Conclusions: The results of this study suggest that the CDT is effective at screening for cognitive impairment in persons with TBI. The CDT could be a valuable supplementary tool in TBI clinics as well as an effective cognitive screening instrument in busy primary care settings. [ABSTRACT FROM AUTHOR]

Objective Systemic anticoagulation remains the standard for acute lower extremity (LE) deep venous thrombosis (DVT), but growing interest in catheter-directed thrombolysis (CDT) and its potential to reduce the incidence of post-thrombotic syndrome (PTS) has led to advent of ultrasound-accelerated CDT (US-CDT). Few studies to date have examined the outcomes of US-CDT against traditional CDT (T-CDT). Methods This is a retrospective, single-center review of all patients treated for acute LE DVT over a five-year period with either US- and T-CDT. Patients were stratified based on demographics, presentation, co-morbidities, risk factors, and peri-procedural data. Results Seventy-six limbs in 67 patients were treated; 51 limbs in 42 patients were treated with US-CDT, and 25 limbs in 25 patients were treated with T-CDT. Adjuncts include: pharmacomechanical thrombolysis ( n = 28 vs. 20, p = 0.04), angioplasty ( n = 22 vs. 18, p = 0.11), stenting ( n = 30 vs. 6, p ≤ 0.001), and IVC filter insertion ( n = 5 vs. 0, p = 0.07). Mean lysis times were 21 ± 1.7 and 24 ± 1.8 h for US- and T-CDT, respectively ( p = 0.26). Thirty (25 ultrasound, 5 traditional) limbs had complete lysis. Thirty-one (22 ultrasound, 9 traditional) limbs had incomplete lysis. Fifteen (4 ultrasound, 11 traditional) limbs had ineffective lysis ( p = 0.002 in favor of ultrasound). Four patients (3 US-CDT, 1 T-CDT) had recurrent ipsilateral thrombosis within 30 days ( p = 0.60). By Kaplan-Meier analysis, there were no significant difference between primary patency, primary-assisted patency, secondary patency, re-thrombosis, and recurrent symptoms at 6, 12, and 24 months. Conclusion US-CDT does not significantly improve mid-term patencies but results in greater acute clot burden reduction in patients with acute LE DVTs compared to T-CDT, which may be beneficial in reducing the long-term incidence of PTS. [ABSTRACT FROM AUTHOR]

Clostridium difficile is the cause of antibiotics-associated diarrhea and pseudomembranous colitis. The pathogen produces three protein toxins: C. difficile toxins A (TcdA) and B (TcdB), and C. difficile transferase toxin (CDT). The single-chain toxins TcdA and TcdB are the main virulence factors. They bind to cell membrane receptors and are internalized. The N-terminal glucosyltransferase and autoprotease domains of the toxins translocate from low-pH endosomes into the cytosol. After activation by inositol hexakisphosphate (InsP6), the autoprotease cleaves and releases the glucosyltransferase domain into the cytosol, where GTP-binding proteins of the Rho/Ras family are mono- O-glucosylated and, thereby, inactivated. Inactivation of Rho proteins disturbs the organization of the cytoskeleton and affects multiple Rho-dependent cellular processes, including loss of epithelial barrier functions, induction of apoptosis, and inflammation. CDT, the third C. difficile toxin, is a binary actin-ADP-ribosylating toxin that causes depolymerization of actin, thereby inducing formation of the microtubule-based protrusions. Recent progress in understanding of the toxins' actions include insights into the toxin structures, their interaction with host cells, and functional consequences of their actions. [ABSTRACT FROM AUTHOR]

Carbohydrate-deficient transferrin (CDT) is a glycoform profile of serum transferrin that increases in response to sustained high alcohol intake and over the last decades has become an important alcohol biomarker with clinical and forensic applications. However, the wide range of CDT measurement procedures has resulted in lack of uniform results and reference limits, and hampered comparison of results. In 2005, the IFCC therefore founded a special working group (WG) aiming for standardisation of CDT measurement. This review summarises the history of CDT and the actions taken by the WG-CDT. Initial steps included the definition of the measurand (serum disialotransferrin to total transferrin fraction expressed in %), and the determination of a well-defined anion-exchange HPLC procedure as the candidate reference measurement procedure (cRMP). Subsequent achievements were the establishment of a network of reference laboratories to perform the cRMP, setting a reference interval, and development of a reference material based on human serum for which the laboratory network assign values. Using a set of reference materials for calibration allowed for achieving equivalence of results of all present CDT measurement procedures. The final steps of the WG-CDT have been a full validation of the cRMP to make it an IFCC approved RMP, and providing guidance for international standardisation of all CDT measurement procedures. [ABSTRACT FROM AUTHOR]

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a complete Tcd pathogenicity locus and achieve similar colonization densities. However, disease severity varies from lethal to avirulent infections. Genomic analysis of avirulent isolates reveals a 69-bp deletion in the cdtR gene, which encodes a response regulator for binary toxin expression. Deleting the 69-bp sequence in virulent R20291 strain renders it avirulent in mice with reduced toxin gene transcription. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile isolates without reducing colonization and persistence. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis. [Display omitted] • Clinical ST1 C. difficile isolates with identical PaLoc can differ remarkably in virulence • Two avirulent C. difficile isolates remain avirulent in immune-deficient and germ-free mice • Avirulent C. difficile isolates contain a deletion in the regulatory gene for binary toxin • CdtR regulates Tcd and CDT toxins, thus broadly impacting the virulence of C. difficile Dong et al. show that clinical ST1 C. difficile isolates with identical pathogenicity loci have variable virulence in mice. A natural deletion within the regulatory gene (cdtR) for binary toxin attenuates virulence in epidemic ST1 C. difficile isolates without reducing colonization and persistence. [ABSTRACT FROM AUTHOR]

• This visualized therapeutic platform can eradicate and accurately image bacteria, and real-time monitor treatment progress. • The aptamer functionalized and NIR responsive CuS@Pt-Au/Apt NPs integrate targeting/CDT/PTT for bacterial infection therapy. • This research addresses the application limitation of nanozymes and effectively treats chronic wounds in diabetic mice. The bacterial infection of chronic wounds caused by diabetes has imposed a significant burden on society and families. Therefore, the collaborative and emerging antibacterial strategies are urgently designed and invented to reduce the burden of bacteria on wounds. Herein, an aptamer functionalized and near-infrared light responsive nano-antibacterial material (CuS@Pt-Au/Apt NPs) based on cascaded nanozymes is successfully constructed for the synergistic therapy of wound infection in diabetic mice. In vitro performance assays verify that CuS@Pt-Au/Apt NPs exhibit the sustained release of hydroxyl radical (·OH) and excellent photothermal properties. Varies in vitro antibacterial experiments demonstrate that the minimum inhibitory concentrations (MICs) of CuS@Pt-Au/Apt against Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) are both 128 μg·mL−1 under NIR irradiation and glucose catalysis, while validate the efficient in vitro bactericidal activity, significant glutathione consumption and its antibacterial mechanism. In vivo anti-infection assays prove that CuS@Pt-Au/Apt NPs perform the best cutaneous wound healing capability with a remaining infected area of <2% for bacterial infection of diabetes, and significantly reduce the occurrence of inflammation at the infected wounds. This antibacterial strategy integrating targeting, chemodynamic therapy (CDT) and photothermal therapy (PTT) not only achieves synergistic and enhanced antimicrobial effects, but also addresses the limitations of nanozymes and promotes their biomedical applications. [ABSTRACT FROM AUTHOR]

Isolaram-se estirpes de Campylobacter spp. em amostras de carcaças (n=65), fezes (n=65) e linfonodos mesentéricos (n=65) de suínos abatidos em frigoríficos do estado de São Paulo e detectaram, pela técnica da Multiplex-PCR, a presença do complexo de genes cdt, responsáveis pela expressão do fator de virulência da toxina CDT. Do total de 195 amostras de origem suína, Campylobacter spp. foi isolado de 31 (15,9%), sendo 29 (93,6%) de amostras de suabe retal, 1/65 (3,2%) de suabe de carcaça e um (3,2%) de linfonodo. Vinte e oito estirpes de C. coli foram positivas para a detecção dos genes cdt, e três estirpes de C. jejuni foram negativas para a detecção desses genes. Foi detectada, pela primeira vez no estado de São Paulo, a presença dos genes cdt em 100% das estirpes de Campylobacter coli provenientes de suínos abatidos em frigoríficos.

Timely identification of excessive alcohol use and its potential complications is a prerequisite for successful treatment. Several routine tests have been used in laboratories that may help in diagnosing alcoholism, such as determination of MCV, AST, ALT, GGT, but it has been shown that they lack specificity and sensitivity. Contemporary biomarkers are increasingly being used today that may due to their unique characteristics help in discovering the onset of chronic alcohol abuse, as well as in abstinence and relapse monitoring. The term carbohydrate-deficient transferrin (CDT) stands for a small group of human transferrin isoforms (asialo, monosialo, and disialotran sferrin) with a lower degree of glycosylation in comparison to the dominant transferrin isoform (tetrasialotransferrin). Persons consuming large quantities of alcohol (≥50-80 g daily) over a period of at least two weeks have increased concentrations of transferrin isoforms lacking one (disialo transferrin) or both (asialotran - sferrin) carbohydrate chains. In this paper the traditional markers of chronic alcohol abuse (GGT, AST, ALT, and MCV) were determined, as well as the new biomarker CDT, after which diagnostic evaluation was performed and their usability and clinical value in routine laboratory practice were estimated. These markers were also determined in heavy alcoholics on admission into hospital and after two weeks of therapy, with the aim of estimating their diagnostic value for abstinence and relapse monitoring.

Small heat shock proteins (sHSP) are a diverse group of proteins and are highly abundant in plant species. Although majority of these sHSPs were shown to express specifically in seed, their potential function in seed physiology remains to be fully explored. Our proteomic analysis revealed that OsHSP18.2, a class II cytosolic HSP is an aging responsive protein as its abundance significantly increased after artificial aging in rice seeds. OsHSP18.2 transcript was found to markedly increase at the late maturation stage being highly abundant in dry seeds and sharply decreased after germination. Our biochemical study clearly demonstrated that OsHSP18.2 forms homooligomeric complex and is dodecameric in nature and functions as a molecular chaperon. OsHSP18.2 displayed chaperone activity as it was effective in preventing thermal inactivation of Citrate Synthase. Further, to analyze the function of this protein in seed physiology, seed specific Arabidopsis overexpression lines for OsHSP18.2 were generated. Our subsequent functional analysis clearly demonstrated that OsHSP18.2 has ability to improve seed vigor and longevity by reducing deleterious ROS accumulation in seeds. In addition, transformed Arabidopsis seeds displayed better performance in germination and cotyledon emergence under adverse conditions as well. Collectively, our work demonstrates that OsHSP18.2 is an aging responsive protein which functions as a molecular chaperon and possibly protect and stabilize the cellular proteins from irreversible damage particularly during maturation drying, desiccation and aging in seeds by restricting ROS accumulation and thereby improves seed vigor, longevity and seedling establishment.

This paper puts forward a new method for the transferrin (Tf) glycoform analysis in body fluids that involves the formation of a transferrin-terbium fluorescent adduct (TfFluo). The key idea is to validate the analytical procedure for carbohydrate-deficient transferrin (CDT), a traditional biochemical serum marker to identify chronic alcohol abuse. Terbium added to a human body-fluid sample produced TfFluo. Anion exchange HPLC technique, with fluorescence detection ( λ 298 nm and λ 550 nm), permitted clear separation and identification of Tf glycoform peaks without any interfering signals, allowing selective Tf sialoforms analysis in human serum and body fluids (cadaveric blood, cerebrospinal fluid, and dried blood spots) hampered for routine test. Serum samples ( n = 78) were analyzed by both traditional absorbance (Abs) and fluorescence (Fl) HPLC methods and CDT% levels demonstrated a significant correlation ( p < 0.001 Pearson). Intra- and inter-runs CV% was 3.1 and 4.6%, respectively. The cut-off of 1.9 CDT%, related to the HPLC Abs proposed as the reference method, by interpolation in the correlation curve with the present method demonstrated a 1.3 CDT% cut-off. Method comparison by Passing-Bablok and Bland-Altman tests demonstrated Fl versus Abs agreement. In conclusion, the novel method is a reliable test for CDT% analysis and provides a substantial analytical improvement offering important advantages in terms of types of body fluid analysis. Its sensitivity and absence of interferences extend clinical applications being reliable for CDT assay on body fluids usually not suitable for routine test. [ABSTRACT FROM AUTHOR]

Carbohydrate-deficient transferrin (CDT) is used as a biomarker of sustained high alcohol consumption. The currently available measurement procedures for CDT are based on various analytical techniques (HPLC, capillary electrophoresis, nephelometry), some differing in the definition of the analyte and using different reference intervals and cut-off values. The Working Group on Standardization of CDT (WG-CDT), initiated by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), has validated an HPLC candidate reference measurement procedure (cRMP) for CDT (% disialotransferrin to total transferrin based on peak areas), demonstrating that it is suitable as a reference measurement procedure (RMP) for CDT. Presented is a detailed description of the cRMP and its calibration. Practical aspects on how to treat genetic variant and so-called di-tri bridge samples are described. Results of method performance characteristics, as demanded by ISO 15189 and ISO 15193, are given, as well as the reference interval and measurement uncertainty and how to deal with that in routine use. The correlation of the cRMP with commercial CDT procedures and the performance of the cRMP in a network of laboratories are also presented. The performance of the CDT cRMP in combination with previously developed commutable calibrators allows for standardization of the currently available commercial measurement procedures for CDT. The cRMP has recently been approved by the IFCC and will be from now on be known as the IFCC-RMP for CDT, while CDT results standardized according to this RMP should be indicated as CDT IFCC . [ABSTRACT FROM AUTHOR]

Enterohemorrhagic Escherichia coli (EHEC) O157:H7/NM strains are significant foodborne pathogens intensively studied, while other sero- and pathotypes of the O157 serogroup only began to receive more attention. Here we report the first genome sequence of a cytolethal distending toxin (CDT-V) producing E. coli O157:H43 strain (T22) isolated from cattle. The genome consists of a 4.9 Mb chromosome assembled into three contigs and one plasmid of 82.4 kb. Comparative genomic investigations conducted with the core genomes of representative E. coli strains in GenBank ( n = 62) confirmed the separation of T22 from the EHEC and enteropathogenic (EPEC) O157 lineages. Gene content based pangenome analysis revealed as many as 261 T22-specific coding sequences without orthologs in EDL933 EHEC O157 prototypic and two phylogenetically related commensal E. coli strains. The genome sequence revealed 10 prophage-like regions which harbor several virulence-associated genes including cdt and heat-labile enterotoxin (LT-II) encoding operons. Our results indicate that the evolutionary path of T22 is largely independent from that of EHEC and EPEC O157:H7/NM strains. Thus, the CDT-producing T22 E. coli O157:H43 strain represents a unique lineage of E. coli O157. [ABSTRACT FROM AUTHOR]

Objective: The Clock Drawing Test (CDT) is widely used as a screening tool for discriminating cognitively normal individuals from patients with mild dementia. The aim of present study was to provide normative values for a 10-point quantitative scoring system proposed by Rouleau and colleagues (1992), including CDT total score and subscales score assessing representation of clock face (RC), layout of numbers (LN), and position of hands (PH), in a large sample of Italian healthy individuals. Method: Eight hundred and seventy-two Italian healthy participants (483 women; age range 20-94 years) with educational level from primary school to university underwent CDT and Mini Mental State Examination (MMSE). Results: Multiple linear regression analysis revealed that age and education significantly influenced CDT total score and its subscale scores. Moreover, a significant effect of gender was found only in RC subscale. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-off values were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a weakly significant correlation between adjusted CDT total score and adjusted MMSE scores. Conclusions: The present study provided normative data for the Rouleau and colleagues version of CDT in an Italian sample, useful for clinical and research purposes. [ABSTRACT FROM AUTHOR]

The simplicity of the pen-and-paper game Sprouts hides a surprising combinatorial complexity. We describe an optimisation called boundary matching that accommodates this complexity to allow move generation for Sprouts games of arbitrary size at interactive speeds. This extended version of the paper also describes methods for plotting and visualising Sprouts moves, using a conforming Delaunay triangulation of the game's underlying geometry. [ABSTRACT FROM AUTHOR]

Carbohydrate-deficient transferrin (CDT) is a glycoform profile of serum transferrin that increases in response to sustained high alcohol intake and over the last decades has become an important alcohol biomarker with clinical and forensic applications. However, the wide range of CDT measurement procedures has resulted in lack of uniform results and reference limits, and hampered comparison of results. In 2005, the IFCC therefore founded a special working group (WG) aiming for standardisation of CDT measurement. This review summarises the history of CDT and the actions taken by the WG-CDT. Initial steps included the definition of the measurand (serum disialotransferrin to total transferrin fraction expressed in %), and the determination of a well-defined anion-exchange HPLC procedure as the candidate reference measurement procedure (cRMP). Subsequent achievements were the establishment of a network of reference laboratories to perform the cRMP, setting a reference interval, and development of a reference material based on human serum for which the laboratory network assign values. Using a set of reference materials for calibration allowed for achieving equivalence of results of all present CDT measurement procedures. The final steps of the WG-CDT have been a full validation of the cRMP to make it an IFCC approved RMP, and providing guidance for international standardisation of all CDT measurement procedures. [ABSTRACT FROM AUTHOR]

Enterohepatic Helicobacter species are associated with several digestive diseases. Helicobacter pullorum is an emerging human foodborne pathogen, and Helicobacter hepaticus is a mouse pathogen; both species are associated with intestinal and/or hepatic diseases. They possess virulence factors, such as cytolethal distending toxin (CDT). Data indicate that CDT may be involved in chronic inflammatory responses, via its active subunit, CdtB. The proinflammatory properties of the CdtB of H. pullorum and H. hepaticus were assessed on human intestinal and hepatic epithelial cells in vitro. Interleukin 8 expression was evaluated by using wild-type strains and their corresponding CdtB isogenic mutants and by delivering CdtB directly into the cells. Nuclear factor κB nuclear translocation and transcriptomic characteristics in response to CdtB were also evaluated. The CdtB of these Helicobacter species induced nuclear factor κB nuclear translocation and exhibited proinflammatory properties, mainly the expression of T-helper type 17-related genes and genes encoding antimicrobial products also involved in cancer. The Histidine residue in position 265 of the CdtB catalytic site appeared to play a role in the regulation of most of these genes. As for flagellin or lipopolysaccharides, CdtB also induced expression of inflammation-associated genes related to antimicrobial activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hypoxia-irrelevant dual free radical nanogenerator (MnO 2 /GOx/AIBI) is prepared. • MnO 2 /GOx/AIBI shows combined chemodynamic and photothermal dynamic antibacterial property. • MnO 2 /GOx/AIBI can inhibit the biofilm formation and eliminate the bacteria deep in mature biofilm. • MnO 2 /GOx/AIBI exhibits satisfactory treatment effect for in vivo biofilm-infected wound. Well-designed nanocatalysts capable of generating free radicals have recently shown promising potential for treating bacterial biofilm infections. However, the biofilm microenvironments such as hypoxia and over-expressed glutathione (GSH) seriously limit their biomedical applications. To address these issues, we herein construct a dual free radical nanogenerator (MnO 2 /GOx/AIBI) by loading glucose oxidase (GOx) and thermal-labile azo initiator (AIBI) onto the flower-like MnO 2 with high loading capacity for the hypoxia-irrelevant treatment of biofilm-associated bacterial infections. On the one hand, MnO 2 /GOx/AIBI nanocomposites can generate hydroxyl radicals by glucose-fueled cascade catalytic reactions between GOx and MnO 2 for efficient O 2 – and H 2 O 2 -self-supplying chemodynamic therapy (CDT). On the other hand, MnO 2 can provide local photonic hyperpyrexia, which not only triggers the O 2 -independent generation of alkyl radicals for photothermal dynamic therapy (PTDT), but also enhances the CDT efficacy by accelerating the release of Fenton-type Mn2+. Besides, MnO 2 can degrade GSH over-expressed in the infection sites, improving the synergistic CDT/PTDT therapeutic effectiveness by redox dyshomeobasis. The hybrid MnO 2 /GOx/AIBI nanocatalysts exhibit satisfactory in vitro and in vivo antibacterial and antibiofilm performances with minimal toxic side effects. Taken together, the developed hypoxia-irrelevant dual-mode synergistic antibacterial nanoplatform can effectively overcome the interferences of biofilm microenvironments, showing a promising potential for future biomedical applications. [ABSTRACT FROM AUTHOR]

Biofilms have become one of the fundamental issues for chronic infections, while traditional therapies are often ineffective in removing quiescent (persister) cells from biofilms, resulting in a variety of implant-related or nosocomial infections. Recently, bacteriophage (phage) therapy has reflourished in research and clinical trials. However, phage therapy alone manifested many intrinsic defects, including poor biofilm penetration, incomplete clearance of quiescent cells, etc. In this study, a phage-Chlorin e6 (Ce6)-manganese dioxide nanocomposite (PCM) was constructed by mild biomineralization. The results demonstrated that PCM contained both the vigorous activities of host bacterial targeting and efficient delivery of Ce6 to penetrate the biofilm. Assisted with NIR irradiation, robust reactive oxygen species (ROS) was triggered within the biofilm. In the weak acidic and GSH-rich infection niche, PCM was degraded into ultra-small nanosheets, endowing PCM with moderate photothermal therapy (PTT) effects and considerable Mn 2+ release, thus exerting strong chemodynamic therapy (CDT) effects in situ . In vivo application demonstrated that the combination of PCM application and NIR irradiation strikingly reduced the pathogen loading, activated innate and adaptive immunity, promoted neocollagen rearrangement, and attenuated cicatricial tissue formation. Our research may pave a new way for bacterial treatment, biofilm-related infections, and other diseases caused by bacteria.

Klebsiella oxytoca complex ( Ko C) species may overproduce their chromosomal class A OXY β-lactamases, conferring reduced susceptibility to piperacillin-tazobactam, expanded-spectrum cephalosporins and aztreonam. Moreover, since clavulanate maintains its ability to inhibit these enzymes, the resulting resistance phenotype may falsely resemble the production of acquired extended-spectrum β-lactamases (ESBLs). In this work, a collection of 44 Ko C strains of human and animal origin was characterized with whole-genome sequencing (WGS) and broth microdilution (BMD) susceptibility testing. Comparison of ESBL producers ( n  = 11; including CTX-M-15 [ n  = 6] and CTX-M-1 [ n  = 5] producers) and hyperproducers of OXYs ( n  = 21) showed certain phenotypic differences: piperacillin-tazobactam (MIC 90s : 16 versus >64 μg/mL), cefotaxime (MIC 90s : 64 versus 4 μg/mL), ceftazidime (MIC 90s : 32 versus 4 μg/mL), cefepime (MIC 90s : 8 versus 4 μg/mL) and associated resistance to non-β-lactams (e.g., trimethoprim-sulfamethoxazole: 90.9% versus 14.3%, respectively). However, a clear phenotype-based distinction between the two groups was difficult. Therefore, we evaluated 10 different inhibitor-based confirmatory tests to allow such categorization. All tests showed a sensitivity of 100%. However, only combination disk tests (CDTs) with cefepime/cefepime-clavulanate and ceftazidime/ceftazidime-clavulanate or the double-disk synergy test (DDST) showed high specificity (100%, 95.5%, and 100%, respectively). All confirmatory tests in BMD or using the MIC gradient strip did not perform well (specificity, ≤87.5%). Of note, ceftazidime/ceftazidime-avibactam tests also exhibited low specificity (CDT, 87.5%; MIC gradient strip, 77.8%). Our results indicate that standard antimicrobial susceptibility profiles can raise some suspicion, but only the use of cefepime/cefepime-clavulanate CDT or DDST can guarantee distinction between ESBL-producing Ko C strains and those hyperproducing OXY enzymes.

Aims: To examine the shot-term outcomes with catheter-directed thrombolysis (CDT) vs. catheter-directed embolectomy (CDE) for high-risk pulmonary embolism (PE)., Methods and Results: The Nationwide Readmissions Database was utilized to identify hospitalizations with high-risk PE undergoing CDE or CDT from 2016 to 2019. The main outcome was all-cause in-hospital mortality. Propensity score matching was used to compare the outcomes in both groups. Among 3216 high-risk PE hospitalizations undergoing catheter-directed interventions, 868 (27%) received CDE, 1864 (58%) received CDT, and 484 (15%) received both procedures. In the unadjusted analysis, the rate of all-cause in-hospital mortality was not different between CDE and CDT (39.6% vs. 34.2%, P = 0.07). After propensity score matching, there was no difference in the incidence of in-hospital mortality [adjusted odds ratio (aOR): 1.28, 95% confidence interval (CI): 0.95, 1.72, P = 0.10], intracranial haemorrhage (ICH) (adjusted OR 1.57, 95% CI: 0.75, 3.29, P = 0.23), or non-ICH bleeding (aOR: 1.17, 95% CI: 0.85, 1.62, P = 0.33). There were no differences in the length of stay, cost, and 30-day unplanned readmissions between both groups., Conclusion: In this contemporary observational analysis of patients admitted with high-risk PE undergoing CDT or CDE, the rates of in-hospital mortality, ICH, and non-ICH bleeding events were not different., Competing Interests: Conflict of interest: I.W. is a consultant for Magneto Thrombectomy Solutions and PI for Penumbra, Inc. A.S.D. is a consultant and speaker for Abiomed; Cardiovascular Systems, Inc.; and Shockwave. A.W.M. is a consultant and speaker for Boston Scientific., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Small heat shock proteins (sHSPs) are a diverse group of proteins and are highly abundant in plant species. Although majority of these sHSPs were shown to express specifically in seed, their potential function in seed physiology remains to be fully explored. Our proteomic analysis revealed that OsHSP18.2, a class II cytosolic HSP is an aging responsive protein as its abundance significantly increased after artificial aging in rice seeds. OsHSP18.2 transcript was found to markedly increase at the late maturation stage being highly abundant in dry seeds and sharply decreased after germination. Our biochemical study clearly demonstrated that OsHSP18.2 forms homooligomeric complex and is dodecameric in nature and functions as a molecular chaperone. OsHSP18.2 displayed chaperone activity as it was effective in preventing thermal inactivation of Citrate Synthase. Further, to analyze the function of this protein in seed physiology, seed specific Arabidopsis overexpression lines for OsHSP18.2 were generated. Our subsequent functional analysis clearly demonstrated that OsHSP18.2 has ability to improve seed vigor and longevity by reducing deleterious ROS accumulation in seeds. In addition, transformed Arabidopsis seeds also displayed better performance in germination and cotyledon emergence under adverse conditions. Collectively, our work demonstrates that OsHSP18.2 is an aging responsive protein which functions as a molecular chaperone and possibly protect and stabilize the cellular proteins from irreversible damage particularly during maturation drying, desiccation and aging in seeds by restricting ROS accumulation and thereby improves seed vigor, longevity and seedling establishment. [ABSTRACT FROM AUTHOR]

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The detection of carbohydrate-deficient transferrin (CDT) in serum is widely accepted to identify chronic alcohol consumption over the previous two weeks, but minor ethanol metabolites detected in hair often complete the information obtained. In particular, ethylglucuronide and cocaethylene (a marker of simultaneous intake of cocaine and alcohol) allow correct interpretation of data obtained in forensic cases. We refer to a negative CDT value obtained from a serum sample collected during hospitalization of a man admitted for cardiac arrest who died about 14 h later. Clinical analysis performed on admission showed a high ethanol level and a positive urinary screening for cocaine. The toxicological analyses of post-mortem samples found cocaine metabolites in his urine and blood. The negative CDT level suggested the ethanol concentration at admission to be an acute episode. Cocaine and cocaethylene well above the cut-off suggested by the literature were found in hair analyzed for the entire length (about 1 cm). Ethylglucuronide detected on the same hair sample confirmed chronic abuse of ethanol in the previous month, at least. The present report suggests caution in the interpretation of biomarkers of alcohol abuse, encouraging the detection of more than one marker to avoid misinterpretation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Micromachined diamond tips have become the ultimate choice for the electrical probing of semiconductor devices at the nanometer scale because of the required high pressures in the GPa range. Although state-of-the-art full diamond tips (FDTs) show an ultra-high spatial resolution of 1 nm, they are suffering from the limited electrical conductivity of the interfacial diamond layer resulting in an overall lower dynamic range. Conventional coated diamond tips (CDTs) on the other hand show a higher electrical conductivity but their core Si tips are prone to breaking off close to the apex due to the high lateral forces during scanning. Therefore, we developed in this work so-called overcoated diamond tips (ODTs) which are combining the advantages of the high mechanical stability of molded FDTs with the higher conductivity of CDTs. The key is the local underetching of a first molded diamond tip and the subsequent growth of a 50–150 nm thin boron-doped diamond layer onto the interfacial diamond layer. The resulting ODT structure is attached to a metal cantilever and is used for electrical atomic force microscopy (AFM) measurements. The fabricated ODTs are mechanically stable and show a higher conductivity than FDTs. This work presents the probe and fabrication scheme, shows manufactured probe devices and demonstrates their performance in electrical AFM measurements. [ABSTRACT FROM AUTHOR]

The concentration detection threshold (CDT) is the concentration of particles in solution beyond which a (serial dilution) assay detects particle presence. By our account, CDTs typically are not estimated but are fixed at some value. Setting a CDT to zero ( $$d=0$$ ) implies perfect detection, a common assumption, and setting $$d>0$$ gives results that are 'denominated' in units of $$d$$ , i.e., are relative to the choice of $$d$$ . Using multiple, different serial dilution assays, each with its own CDT, we choose a 'reference assay,' to which we assign a fixed CDT value, to obtain relative estimates of the remaining assays' CDTs and the underlying particle concentration. We present the CDTs as a novel way to account for or to compare different serial dilution assays, 'sensitivities'. We apply our methodology to data from four assays of the presence of bacterial ( B. abortus) antibodies in the serum of elk in the Greater Yellowstone Ecosystem, where transmission of brucellosis-the disease ensuing from infection-to commercial livestock is managed by the Wyoming Game and Fish Department to avoid the primary symptom of abnormal fetal abortion. Results agree qualitatively with the more traditional notion of sensitivity as the true positive rate. [ABSTRACT FROM AUTHOR]

In this study, glucose oxidase (GOx) is mineralized with calcium phosphate (CaP) circled Cu 2 O/Pt nanozyme to form a core–shell structural CuPt-GOx-CaP nanoreactor by a one-step biomimetic mineralization method. The biodegradable and acidity-responsive CuPt-GOx-CaP nanoreactor can be used for starvation and photothermal-enhanced cascade reaction antibacterial therapy. And the release of copper ions have been used for enhanced angiogenesis. [Display omitted] • CuPt-GOx-CaP nanoreactor with pH response. • The nanoreactor with starvation/photothermal/chemodynamic therapy. • The nanoreactor depletes Gs and releases O 2 through an enzymatic reaction. • CuPt-GOx-CaP nanoreactor release Cu2+ and promote angiogenesis. Persistent inflammation and bacterial infection are common during wound healing, and high blood sugar provides enough nutrients for bacterial growth to make wounds more prone to ulcers. Herein, glucose oxidase (GOx) is mineralized with calcium phosphate (CaP) circled Cu 2 O/Pt nanozyme to form a core–shell structural CaP-GOx-Cu 2 O/Pt (GOx-CaPCuPt) nanoreactor. The prepared biodegradable and acidity-responsive GOx-CaPCuPt nanoreactor can be used for near infrared imaging, photothermal enhanced cascade reaction and antibacterial therapy. Oxidation of glucose (Gs) by the GOx can significantly decrease Gs level for starvation therapy, and the generated H 2 O 2 in this reaction is subsequently converted into highly active hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and O 2 for overcoming hypoxia via triple enzyme like activities (peroxidase, oxidase, and catalase) of Cu 2 O/Pt nanozyme. At the same time, the acidic microenvironment due to the generation of gluconic acid will in turn promote the degradation of the GOx-CuCaP nanoreactor and release of copper ions for enhanced angiogenesis. In addition, Cu 2 O/Pt nanoparticles have strong characteristic absorption in near-infrared region, which can induce a strong photothermal effect (PTT) under the irradiation of 808 nm laser. Under the guidance of near-infrared imaging, the multifunctional nanoreactor can achieve the combination of starvation therapy and PTT-enhanced CDT against Gram -negative and Gram -positive bacteria infectious diseases, which is demonstrated in the staphylococcus aureus infected diabetic rat models. [ABSTRACT FROM AUTHOR]

Background: Breast cancer-related lymphedema (BCRL) after primary therapy is a common condition, causing physical and psychological distress. Decongestive lymphedema therapy (DLT) using multi-layered compression bandages is an effective treatment. We conducted a randomized controlled trial evaluating the use of a specific mobilizing bandage (Mobiderm ® ) on lymphedema volume reduction during the intensive phase of DLT. Methods and Results: Fifty female BCRL patients were randomized to receive either conventional multi-layered bandages or mobilizing bandaging by using Mobiderm. Affected limb volume and excess volume were evaluated at baseline (D0) and after 15 days. The primary outcome was change in affected limb volume after adjustment for baseline. Symptom scores were evaluated by visual analogue scale (VAS); safety and tolerability were also assessed. Baseline characteristics were comparable. Affected limb volume reduction was observed in both study groups after 15 days: by 19.0% in the Mobiderm arm and 8.6% in controls (adjusted values). The between-group mean difference in adjusted volume reduction at day 15 was 256 mL (95% confidence interval [CI], 92.5 to 421.3 mL; p  = 0.003) favoring Mobiderm. Reductions in excess volume of 57.3% (Mobiderm) and 25.1% (controls) were observed (adjusted values); with between-group mean difference in adjusted excess volume of 220.2 mL (95% CI, 69.3 to 371.3 mL; p  = 0.006) favoring Mobiderm. Pain/heaviness VAS scores fell significantly in both groups, with mean reductions of 1.84 (Mobiderm) versus 0.83 (control; p  = 0.001). Both regimens were well tolerated. Conclusion: The use of Mobiderm in multilayer compression bandaging shows benefit in lymphedema reduction and in alleviating functional symptoms/pain in patients with BRCL.

Background: Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection., Methods: To determine the contribution of the separate components of CDT during infection, we developed strains of C difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness., Results: Although expression of CDTb without CDTa did not induce significant disease in a mouse model of C difficile infection, we found that complementation of a CDT-deficient C difficile strain with CDTb alone restored virulence in a hamster model of C difficile infection., Conclusions: Overall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection., Competing Interests: Potential conflicts of interest. WAP Jr. is a consultant for TechLab, Inc. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The chromatin dispersion test (CDT) is based on the removal of nuclear proteins under the assumption that cells with fragmented DNA produce a typical halo of circular DNA loops, which is absent in cells with non-fragmented DNA. This method represents a simple, rapid, accurate, highly reproducible, and inexpensive technique to assess nuclear DNA damage in somatic cells. The visualization of DNA damage and the capacity of the test to provide a threshold value to discriminate between high and low levels of cervical lesions would aid in determining the malignant transformation. All of these advantages associated with the CDT protocol could promote this technique as a tool for the quick and reliable diagnosis of cervical epithelial disorders, even at primary-care centers., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H 2 O 2 ) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS 2 /CuO 2 ) is rationally constructed by simply decorating ultrasmall CuO 2 nanodots onto lamellar MoS 2 platelets of hydrangea-like MoS 2 nanocarrier via a covalent Cu-S bond. The MoS 2 /CuO 2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H 2 O 2 produced by acid-triggered decomposition of the decorated CuO 2 into hydroxyl radical (•OH). Meanwhile, the MoS 2 /CuO 2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu 2+ and Mo 6+ ) for enhanced CDT. More importantly, MoS 2 support can promote the conversion of Cu 2+ to Cu + by a co-catalytic reaction based on the Mo 4+ /Mo 6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS 2 /CuO 2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H 2 O 2 ) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS 2 /CuO 2 ) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H 2 O 2 and consuming GSH. Importantly, MoS 2 support can promote the conversion of Cu 2+ to Cu + by the Mo 4+ /Mo 6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS 2 /CuO 2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

We herein report a 99-year-old woman with hypertension and dyslipidemia. From the beginning of August 20XX, significant edema from the left thigh to the toes had been observed, so she had consulted her previous doctor. She had been suspected of having cellulitis and was given antibiotics, but no improvement in her symptoms was noted, so she was transferred to our hospital. The edema of the lower leg was localized to the left lower leg only, and the D-dimer level was as high as 16.6 μg/mL at her visit to the emergency room, so deep vein thrombosis (DVT) was suspected, and the patient received immediate hospitalization. Continuous administration of undifferentiated heparin was started, and lower extremity venous ultrasound was performed. As a result, central-type DVT extending from the left iliac vein to the common iliac vein bifurcation was observed. However, despite administering inferior vena cava (IVC) filter into under the renal vein, and changing heparin to edoxaban 30 mg, no improvement in the lower limb edema was observed. Therefore, catheter-based thrombolysis (CDT) was started on day 11 of illness, and continuous administration of urokinase was started via the catheter. Heparin and edoxaban were not used in combination in order to reduce the risk of bleeding. The edema gradually improved, and after confirming that the thrombus had completely disappeared on lower extremity venous ultrasound, the catheter was removed on day 14 (day 24 of illness) after starting CDT. The IVC filter was also removed, and prescription of edoxaban 30 mg was restarted. Since the patient had used a walking frame at home, she started rehabilitation from the initiation of CDT therapy and was discharged once she was able to use a self-sustaining portable toilet. The basic treatment for DVT is anticoagulant therapy; however, a large amount of thrombosis was observed in the present case, and no marked improvement was observed with conventional anticoagulant therapy. As the patient was particularly elderly, and considering that it was important to improve the edema promptly in order to maintain her activities of daily living, we performed CDT treatment and concluded that it was very effective in this case. However, the CDT procedure for DVT has yet to be standardized, and there are few cases of CDT treatment, especially for such super-elderly patients. In the current aging society, the incidence of DVT diseases is increasing, and in cases such as the present case, anticoagulation therapy alone and CDT therapy should be considered and implemented after careful consideration of the bleeding risk.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment., Competing Interests: Conflicts of interest The author reports no conflicts of interest in relation to this work., (Copyright © 2023. Published by Elsevier Inc.)