Fabrication of well-aligned Co-MOF arrays through a controlled and moderate process for the development of a flexible tetrabromobisphenol A sensor.

Tetrabromobisphenol A (TBBPA) has attracted a great deal of attention due to its side effects and potential bioaccumulation properties. It is of great importance to construct and develop novel electrochemical sensors for the sensitive and selective detection of TBBPA. In the present study, cobalt (Co) based metal-organic frameworks (MOFs) were synthesized on carbon cloth (CC) by using cobalt nitrate hexahydrate and 2-methylimidazole. The morphological characterization was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The results showed that Co-MOFs/CC have a leaf-like structure and abundant surface functional groups. The electrochemical properties of the sensor were investigated by differential pulse voltammetry (DPV). The effects of different ratios of metal ions to organic ligands, reaction temperature, time, concentration, pH value of the electrolyte, and incubation time on the oxidation peak current of TBBPA were studied. Under the optimal conditions, the linear range of the designed sensor was 0.1 µM-100 µM, and the limit of detection was 40 nM. The proposed sensor is simple, of low cost and efficient, which can greatly facilitate the detection tasks of environmental monitoring workers.

DNAzyme-Derived Aptamer Reversely Regulates the Two Types of Enzymatic Activities of Covalent-Organic Frameworks for the Colorimetric Analysis of Uranium.

Nanozymes are nanomaterials with enzyme-mimetic activity. It is known that DNA can interact with various nanozymes in different ways, enhancing or inhibiting the activity of nanozymes, which can be used to develop various biosensors. In this work, we synthesized a photosensitive covalent-organic framework (Tph-BT) as a nanozyme, and its oxidase and peroxidase activities could be reversely regulated by surface modification of single-stranded DNA (ssDNA) for the colorimetric detection of UO22+. Tph-BT exhibits excellent oxidase activity and weak peroxidase activity, and it is surprising to find that the UO22+-specific DNA aptamer can significantly inhibit the oxidase activity while greatly enhancing the peroxidase activity. The present UO22+ interacts with the DNA aptamer to form secondary structures and detaches from the surface of Tph-BT, thereby restoring the enzymatic activity of Tph-BT. Based on the reversed regulation effects of the DNA aptamer on the two types of enzymatic activities of Tph-BT, a novel "off-on" and "on-off" sensing platform can be constructed for the colorimetric analysis of UO22+. This research demonstrates that ssDNA can effectively regulate the different types of enzymatic activities of single COFs and achieve the sensitive and selective colorimetric analysis of radionuclides by the naked eye.

Reversed Regulation Effects of ssDNA on the Mimetic Oxidase and Peroxidase Activities of Covalent Organic Frameworks.

Nanomaterials with enzyme mimetic activity have attracted extensive attention, especially in the regulation of their catalytic activities by biomolecules or other polymers. Here, a covalent organic framework (Tph-BT COF) with excellent photocatalytic activity is constructed by Schiff base reaction, and its mimetic oxidase activity and peroxidase activity is inversely regulated via single-stranded DNA (ssDNA). Under light-emitting diode (LED) light irradiation, Tph-BT exhibited outstanding oxidase activity, which efficiently catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue oxTMB, and ssDNA, especially those with poly-thymidine (T) sequences, can significantly inhibit its oxidase activity. On the contrary, Tph-BT showed weak peroxidase activity, and the presence of ssDNA, particularly poly-cytosine (C) sequences, can remarkably enhance the peroxidase activity. The influence of base type, base length, and other factors on the activities of two enzymes is also studied, and the results reveal that the adsorption of ssDNA on the surface of Tph-BT prevented intersystem crossing (ISC) and energy transfer processes to reduce 1 O2 generation, while the electrostatic interaction between ssDNA and TMB enhanced Tph-BT's affinity for TMB to facilitate the electron transfer from TMB to • OH. This study investigates multitype mimetic enzyme activities of nonmetallic D-A conjugated COFs and demonstrates their feasibility of regulation by ssDNA.

Analysis of the Optic Nerve Head Microcirculation Using Optical Coherence Tomography Angiography and the Upstream Macrocirculation Using Color Doppler Imaging in Low-Tension and High-Tension Glaucoma Patients.

INTRODUCTION: The aim of the study was to analyze the optic nerve head (ONH) microcirculation using optical coherence tomography angiography (OCT-A) and the upstream macrocirculation using color Doppler imaging (CDI) in low-tension and high-tension glaucoma (LTG and HTG, respectively). METHODS: This cross-sectional study included 67 eyes of 67 HTG patients, 55 eyes of 55 LTG patients, and 42 eyes of 42 healthy controls. We recorded the complete ophthalmological examination, visual fields, retinal nerve fiber layer (RNFL) thickness, ONH vessel density (VD) measured using OCT-A, peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) measured using CDI. SPSS software was used for data analysis. Data are presented as mean ± standard deviation or median (interquartile range) and compared using t test or Mann-Whitney U test, as appropriate. Pearson χ2 test or Fisher's exact test was used for comparisons, as appropriate. Pearson correlation analysis was used to evaluate the correlations between variables. p < 0.05 was considered statistically significant. RESULTS: The ONH VD and RNFL thickness were considerably lower in glaucomatous eyes than in healthy eyes (both p < 0.001). Compared with the HTG group, the LTG group had lower VD in the peripapillary region (p = 0.027). Compared with the healthy group, the HTG group had lower PSV (p = 0.029 and = 0.023, respectively), lower EDV (p = 0.023 and <0.001, respectively), and higher RI (p = 0.019 and = 0.006, respectively) of the internal carotid artery (ICA) and central retinal artery (CRA). The LTG group had lower PSV (p = 0.015 and <0.001, respectively) and EDV (p = 0.047 and = 0.001, respectively) of the ophthalmic artery (OA) and CRA. The LTG group had lower PSV of CRA than the HTG group (p = 0.034). In glaucomatous eyes, peripapillary VD had a significant association with the mean defect (p < 0.001) and RNFL thickness (p < 0.001), but not with the other CDI indices (all p > 0.05). CONCLUSION: The ONH microcirculation and upstream macrocirculation of the large arteries exhibited differences in the blood flow characteristics between the LTG and HTG groups. These differences may improve our understanding of glaucoma. There was no correlation between the characteristics of the ONH microcirculation and the upstream macrocirculation of large vessels in the LTG and HTG groups.

Status and influencing factors of disease uncertainty among family caregivers of patients with moderate and severe craniocerebral injury: a quantitative and qualitative study.

BACKGROUND: Disease uncertainty widely exists among family caregivers of patients with moderate and severe craniocerebral injury. This negative emotional reaction will reduce the ability of family caregivers to make decisions during the critical stage of the patient, causing serious effects on the rescue and prognosis of patients with moderate and severe craniocerebral injury. Therefore, this article aims to understand the state of the uncertainty of the disease of family caregivers of patients with moderate and severe craniocerebral injury in China, to analyze the influencing factors, and to explore the specific resource of the uncertainty of the disease combined with qualitative study. The outcomes will provide a theoretical basis for formulating an accurate clinical nursing intervention strategy. METHODS: This study was conducted in the neurosurgery ward. A total of 214 family caregivers were evaluated using five previously validated scales: (i) Mishel Uncertainty in Illness Scale for family member, (ii) Simplified Coping Style Questionnaire, (iii) Social Support Rating Scale, and (iv) Self-Rating Anxiety Scale, (v) Zarit Caregiver Burden Interview. Kolmogorov-Smirnov was used to test the normality of the data distribution. The potential determinants of disease uncertainty were evaluated using the univariate statistical analysis. A multivariate linear regression model was adopted to assess the predictors of disease uncertainty in family caregivers of patients with moderate and severe craniocerebral injury. Objective sampling method was used to conduct semi-structured interviews with 17 family caregivers of patients with moderate and severe craniocerebral injury, and Colaizzi 7-step analysis method was used to analyze and summarize the interview data. RESULTS: The evaluated participants exhibited critically high levels of perceived uncertainty. The results of multiple linear regression showed that the influencing factors of family caregivers' disease uncertainty were anxiety, number of other caregivers, GOS, negative coping style, and caregiver burden. The qualitative research focuses on two main topics: the sources of disease uncertainty among family caregivers of patients with moderate and severe craniocerebral injury and experience to cope with the situation. CONCLUSION: The main cause of disease uncertainty of family caregivers of patients with moderate and severe craniocerebral injury is that patients' disease progression and prognosis as well as caregivers' own pressure of responsibility and negative mental status. Furthermore, caregivers' own pressure of responsibility and negative mental status are not clear. Therefore, helping family caregivers adopt positive coping approaches, guiding them to actively seek support from family and society, improving their nursing skills, and understanding of disease progression and prognosis all play an important role in alleviating the uncertainty of the disease.

Discovery of Simple Diacylhydrazine-Functionalized Cinnamic Acid Derivatives as Potential Microtubule Stabilizers.

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N'-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. Notably, compound I23 exhibited the best antiproliferative activity against three cancer lines with IC50 values ranging from 3.36 to 5.99 µM and concurrently afforded a lower cytotoxicity towards the NRK-52E cells. Anticancer mechanism investigations suggested that the highly bioactive compound I23 could potentially promote the protofilament assembly of tubulin, thus eventually leading to the stagnation of the G2/M phase cell cycle of HepG2 cells. Moreover, compound I23 also disrupted cancer cell migration and significantly induced HepG2 cells apoptosis in a dosage-dependent manner. Additionally, the in silico analysis indicated that compound I23 exhibited an acceptable pharmacokinetic profile. Overall, these easily prepared N-cinnamoyl-N'-(substituted)acryloyl hydrazide derivatives could serve as potential microtubule-interacting agents, probably as novel microtubule-stabilizers.

Facile Construction of Covalent Organic Framework Nanozyme for Colorimetric Detection of Uranium.

2D covalent organic frameworks (2D COFs) have been recognized as a novel class of photoactive materials owing to their extended π-electron conjugation and high chemical stabilities. Herein, a new covalent organic framework (Tph-BDP) is facilely synthesized by using a porphyrin derivative and an organic dye BODIPY derivative (5,5-difluoro-2,8-diformyl-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazabori-nin-4-ium-5-uide) as monomers for the first time, and their unique photosensitive properties endow them excellent simulated oxidase activity under 635 nm laser irradiation that can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Further findings demonstrate that the presence of uranium (UO22+ ) can coordinate with imines of the oxidation products of TMB, thus modulating the charge transfer process of the colored products accompanied with intensive aggregation and remarkable color fading. This research provides a preparation strategy for COFs with excellent photocatalytic properties and nanozyme activity, and broadens the applications of the simple colorimetric methods for sensitive and selective radionuclide detection.

CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2.

Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro. In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC.

Overexpression of SLC12A5 is associated with tumor progression and poor survival in ovarian carcinoma.

INTRODUCTION: The solute carrier family 12 member 5 (SLC12A5) gene is playing a putative oncogenic role in colorectal carcinoma. However, the status of SLC12A5 amplification and expression in ovarian carcinoma and its potential clinical and/or prognostic significance has not yet been investigated. METHODS: In the present study, semi-quantitative staining and fluorescence in situ hybridization were used to investigate SLC12A5 protein expression and gene amplification levels. Samples were obtained from archival, formalin-fixed, paraffin-embedded pathological specimens consisting of 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors, and 147 invasive ovarian carcinomas. SLC12A5 immunohistochemical staining results, pathological parameters, and patient prognosis were then evaluated using various statistical models. Patient survival rate was also assessed using receiver-operator curve analysis. RESULTS: Our results revealed no SLC12A5 protein overexpression in normal ovaries. However, 7% of cystadenomas had SLC12A5 protein overexpression along with 17% of borderline tumors and 37% of ovarian carcinomas (P<0.01). Amplification of SLC12A5 was detected in 10.3% of ovarian carcinomas. Further correlational analyses showed that SLC12A5 protein overexpression in ovarian carcinomas was significantly associated with ascending histological grade, pT/pN/pM status, as well as FIGO stage (P<0.05). A subsequent univariate survival analysis of our ovarian carcinoma cohorts resulted in a significant association between SLC12A5 protein overexpression and decreased patient survival (44.3 and 85.9 months for high and low SLC12A5 protein expression, respectively; P<0.001). Importantly, additional multivariate analysis revealed that SLC12A5 protein expression was a significant, independent prognostic factor for overall survival in ovarian carcinoma patients (P=0.003). CONCLUSIONS: Collectively, these findings support the conclusion that SLC12A5 protein overexpression could indicate an invasive and/or aggressive phenotype of ovarian carcinoma. Future work will need to investigate whether SLC12A5 protein can serve as an independent prognostic molecular marker in patients with ovarian carcinoma.

LaVO4: Eu3+ nano-islands onto silica for achieving fluorescence enhancement and their detection of Fe3+ ions and anti-counterfeiting applications.

Rare earth (RE) composite fluorescent materials are favored by researchers in the field of anti-counterfeiting and ion sensing due to their fascinating optical properties. Ultra-small RE fluorescent nanoparticles are anchored on inorganic carriers by a simple preparation method to improve luminous intensity and hydrophilicity, which has not been explored yet. Herein, LaVO4: Eu3+ nano-islands anchored on silica with high fluorescence intensity and easy formation of stable colloidal solution is designed. Through a simple and mild hydrothermal approach, ultra-small LaVO4: Eu3+ nano-islands are highly dispersed on the surface of hierarchical hollow silica sphere (HHSS) to expose more luminescent centers. Remarkably, the stable HHSS@LaVO4: Eu3+ colloidal solution displayed highly sensitive and selective sensor for Fe3+ ions. The "island-sea synergy" structure formed by the LaVO4: Eu3+ nano-islands and the surrounding silica surface makes HHSS@LaVO4: Eu3+ to be an outstanding sensor for the effective detection of iron ions in water. In addition, HHSS@LaVO4: Eu3+ phosphor exhibit unique properties for anti-counterfeiting and encryption applications. These findings provide a promising strategy for the carrierisation of RE luminescent materials to improve optical properties and enable broader applications.

An in-situ strategy to construct uracil-conjugated covalent organic frameworks with tunable fluorescence/recognition characteristics for sensitive and selective Mercury(II) detection.

Previous researches of covalent organic frameworks (COFs) have shown their potential as fluorescent probes, but the regulation of their optical properties and recognition characteristics still remains a challenge, and most of reports required complicated post-decoration to improve the sensing performance. In this context, we propose a novel in-situ strategy to construct uracil-conjugated COFs and modulate their fluorescence properties for sensitive and selective mercury(II) detection. By using 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) and 1,3,6,8-tetrakis(4-aminophenyl)pyrene (TAPPy) as fundamental blocks and 5-aminouraci (5-AU) as the functional monomer, a series of COFs (Py-COFs and Py-U-COFs-1 to Py-U-COFs-5) with tunable fluorescence were solvothermally synthesized through an in-situ Schiff base reaction. The π-conjugated framework serves as a signal reporter, the evenly and densely distributed uracil acts as a mercury(II) receptor, and the regular pores (channels) make the rapid and sensitive detection of the mercury(II) possible. In this research, we manage to regulate the crystalline structure, the fluorescence properties, and the sensing performance of COFs by simply changing the molar ratio of precursors. We expect this research to open up a new strategy for effective and controllable construction of functionalized COFs for environmental analysis.

Psychological resilience is related to postoperative adverse events and quality of life in patients with glioma: a retrospective cohort study.

Background: Psychological resilience has played an increasingly important role in the treatment of different diseases and many glioma patients will experience adverse emotional reactions after being diagnosed. However, it remains unclear whether psychological resilience is related to the adverse events and quality of life of patients with glioma. Methods: Patients with glioma between March 2016 and July 2020 were included in this retrospective cohort study. Psychological resilience was evaluated by the Connor-Davidson resilience scale (CD-RISC) 1 day before surgery. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC QLQ-BN20 were used for the quality of life (QoL) assessment of the included patients. The relationships between psychological resilience and postoperative adverse events/QoL were determined using multivariable logistic and linear regression analysis, respectively. Some patients were evaluated again after admission, and the patients were divided into an increased resilience group and decreased resilience group for subgroup analysis according to the changes between the two CD-RISC scores. All included patients were followed up for at least 6 months. Results: Ninety-seven patients were included in the high resilience group and 284 patients were included in the low resilience group. More neurological complications occurred in the low resilience group than in the high resilience group (18.7% vs. 8.2%, P=0.016). Also, a higher Karnofsky performance scale score and higher psychological resilience contributed to less adverse events. Patients in the high resilience group had higher postoperative global health status scores than those in the low resilience group. Higher educational level, Karnofsky performance scale score, and psychological resilience acted as a protective factor for postoperative QoL. Subgroup analysis showed that the incidence of neurological complications was significantly higher in the decreased resilience group compared to the increased resilience group (22.9% vs. 3.8%, P=0.039). Lastly, better global health status, physical functioning, and role functioning were observed in glioma patients with increased resilience. Conclusions: The incidence of postoperative adverse events and QoL of glioma patients are closely related to their level of preoperative psychological resilience. Psychological counseling may also be a part of improving the prognosis of glioma patients.

Analysis of perioperative negative emotion risk factors in patients with pituitary adenoma and its impact on prognosis: a retrospective study.

Background: Pituitary adenoma (PA) is the third most common tumor in craniocerebral surgery. Most patients will experience varying degrees of negative emotions before and after surgery, which may affect the prognosis of surgery. This study analyzed the perioperative negative emotional risk factors of patients with different characteristics of PA and their impact on prognosis, so as to provide a reference for improving the prognosis of patients with PA. Methods: A total of 234 patients who underwent PA surgery in the Affiliated Hospital of Nantong University from January 2017 to January 2022 were selected as the observation population. The general characteristics of the subjects were collated using a general information questionnaire designed by the researchers. The negative emotions of the patients were evaluated using a Self-rating Anxiety Scale (SAS) and a Self-rating Depression Scale (SDS). The prognosis of patients was determined by assessing the hypophyseal hormone levels. Multiple regression analysis and logistic regression were used to analyze the risk factors of perioperative negative emotions and the effects of negative emotions on patient prognosis. Results: Multiple regression analysis showed that with and without children, education, income, PA type, PA size, and surgical approach were independent factors influencing negative emotions in patients after PA surgery (P<0.05). Logistic regression analysis showed that negative emotion was an independent prognostic factor (P<0.05). Conclusions: There are many factors that affect the anxiety and depression of patients after PA surgery. The family members and medical staff of the patients should take effective measures to relieve the anxiety and depression of the patients so as to improve the prognosis of patients according to the influencing factors.

A new toad species of the genus Brachytarsophrys Tian & Hu, 1983 (Anura, Megophryidae) from Guizhou Province, China.

BACKGROUND: The toads of the genus Brachytarsophrys Tian & Hu, 1983 are distributed in southern China, Myanmar, Vietnam, Laos and northern Thailand. Seven species of the genus have been recognised, of which five of them are known from China so far. NEW INFORMATION: Brachytarsophrysqiannanensis sp. nov., a new species of the short-legged toad genus is here described from southern Guizhou Province, China. Diagnostic characters of the new species are illustrated and comparisons with its congeners are provided. Its validity is also affirmed by its distinct mitochondrial gene sequence divergence with all congeners and its monophyly recovered in the mitochondrial gene-based phylogenetic analyses.

Maelstrom promotes tumor metastasis through regulation of FGFR4 and epithelial-mesenchymal transition in epithelial ovarian cancer.

BACKGROUND: Increasing evidence has indicated that Maelstrom (MAEL) plays an oncogenic role in various human carcinomas. However, the exact function and mechanisms by which MAEL acts in epithelial ovarian cancer (EOC) remain unclear. RESULTS: This study demonstrated that MAEL was frequently overexpressed in EOC tissues and cell lines. Overexpression of MAEL was positively correlated with the histological grade of tumors, FIGO stage, and pT/pN/pM status (p < 0.05), and it also acted as an independent predictor of poor patient survival (p < 0.001). Ectopic overexpression of MAEL substantially promoted invasiveness/metastasis and induced epithelial-mesenchymal transition (EMT), whereas silencing MAEL by short hairpin RNA effectively inhibited its oncogenic function and attenuated EMT. Further study demonstrated that fibroblast growth factor receptor 4 (FGFR4) was a critical downstream target of MAEL in EOC, and the expression levels of FGFR4 were significantly associated with MAEL. (P < 0.05). CONCLUSION: Our findings suggest that overexpression of MAEL plays a crucial oncogenic role in the development and progression of EOC through the upregulation of FGFR4 and subsequent induction of EMT, and also provide new insights on its potential as a therapeutic target for EOC.

Construction of D-A-Conjugated Covalent Organic Frameworks with Enhanced Photodynamic, Photothermal, and Nanozymatic Activities for Efficient Bacterial Inhibition.

Bacterial infection causes serious threats to human life, especially with the appearance of antibiotic-resistant bacteria. Phototherapeutic approaches have become promising due to their noninvasiveness, few adverse effects, and high efficiency. Herein, a covalent organic framework (TAPP-BDP) with a conjugated donor-acceptor (D-A) structure has been constructed for efficient photoinduced bacteriostasis. Under the irradiation with a single near-infrared (NIR) light (λ = 808 nm), TAPP-BDP alone involves triple and synergistic bacterial inhibition based on the integration of photodynamic, photothermal, and peroxidase-like enzymatic activities. The unique D-A structure endows TAPP-BDP with a narrow energy band gap, improving its photodynamic and nanozyme activities to generate reactive oxygen species (ROS) to realize the broad-spectrum bactericidal activity. The extended π-conjugated skeleton of TAPP-BDP results in enhanced absorption in NIR, and the remarkable photothermal activity can increase the temperature up to 65 °C to cause efficient bacterial degeneration. TAPP-BDP shows excellent antibacterial efficiency against both Gram-negative and Gram-positive bacteria. Animal experiments further suggest that TAPP-BDP can effectively heal wounds infected with Staphylococcus aureus in living systems.

Appropriate thromboprophylaxis in hospitalized cancer patients.

BACKGROUND: Cancer is associated with an increased risk of venous thromboembolism (VTE) in hospitalized patients. Despite availability of evidence-based guidelines recommending thromboprophylaxis in cancer patients, many cancer patients do not receive appropriate thromboprophylaxis. This study provides a large, real-world analysis of the rates of thromboprophylaxis use in hospitalized cancer patient discharges. METHODS: Hospital discharge information from the Premier Perspective inpatient database from January 2002-September 2005 was used. Included discharges had a principal diagnosis of cancer, were aged 40 years or older, had a length of hospital stay of 6 days or more, and had no contraindications for anticoagulation. The rate of appropriate VTE prophylaxis was determined according to the 7th American College of Chest Physicians guidelines, taking into account mechanical compression and chemoprophylaxis, dosage of anticoagulant, and duration of therapy. RESULTS: A total of 72,337 cancer discharges with an indication for thromboprophylaxis were identified (30,124 surgical, 42,213 nonsurgical). The overall rate of any level of VTE prophylaxis was 53.6%; however, the rate of appropriate thromboprophylaxis (according to the 7th ACCP guidelines) was 27.0% (27.0% surgical, 27.1% nonsurgical). The most common reason for inappropriate prophylaxis (46.0% of all discharges) was no prophylaxis received, despite having no contra-indication to anticoagulation. CONCLUSIONS: This study highlights that despite the presence of evidence-based guidelines, appropriate thromboprophylaxis is severely underused in all types of at-risk cancer patients. Greater efforts are needed to improve the implementation of guidelines, and to ensure that more cancer patients receive appropriate thromboprophylaxis.

Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy.

Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.

The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy.

Mitogen-activated protein kinase kinase kinase (MEKK1) mediates activation of c-Jun NH(2)-terminal kinase (JNK). Although previous studies using cultured cardiac myocytes have suggested that the MEKK1-JNK pathway plays a key role in hypertrophy and apoptosis, its effects in cardiac hypertrophy and apoptosis are not fully understood in adult animals in vivo. We examined the role of the MEKK1-JNK pathway in pressure-overloaded hearts by using mice deficient in MEKK1. We found that transverse aortic banding significantly increased JNK activity in Mekk1(+/+) but not Mekk1(-/-) mice, indicating that MEKK1 mediates JNK activation by pressure overload. Nevertheless, pressure overload caused significant levels of cardiac hypertrophy and expression of atrial natriuretic factor in Mekk1(-/-) animals, which showed higher mortality and lung/body weight ratio than were seen in controls. Fourteen days after banding, Mekk1(-/-) hearts were dilated, and their left ventricular ejection fraction was low. Pressure overload caused elevated levels of apoptosis and inflammatory lesions in these mice and produced a smaller increase in TGF-beta and TNF-alpha expression than occurred in wild-type controls. Thus, MEKK1 appears to be required for pressure overload-induced JNK activation and cytokine upregulation but to be dispensable for pressure overload-induced cardiac hypertrophy. MEKK1 also prevents apoptosis and inflammation, thereby protecting against heart failure and sudden death following cardiac pressure overload.

Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy.

Activation of mammalian sterile 20-like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity-dependent manner. In vivo, cardiac-specific overexpression of Mst1 in transgenic mice results in activation of caspases, increased apoptosis, and dilated cardiomyopathy. Surprisingly, however, Mst1 prevents compensatory cardiac myocyte elongation or hypertrophy despite increased wall stress, thereby obscuring the use of the Frank-Starling mechanism, a fundamental mechanism by which the heart maintains cardiac output in response to increased mechanical load at the single myocyte level. Furthermore, Mst1 is activated by ischemia/reperfusion in the mouse heart in vivo. Suppression of endogenous Mst1 by cardiac-specific overexpression of dominant-negative Mst1 in transgenic mice prevents myocyte death by pathologic insults. These results show that Mst1 works as both an essential initiator of apoptosis and an inhibitor of hypertrophy in cardiac myocytes, resulting in a previously unrecognized form of cardiomyopathy.