Effect of topical latanoprost on choroidal thickness and vessel area in Guinea pigs.

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p > 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 µm at baseline and 0.04 ± 0.06 µm after 2 weeks of treatment (SD-OCT; p > 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 µm2 after treatment (p = 0.04). While this study was limited to otherwise untreated young adult guinea pigs, the possibility that choroidal vessel enlargement contributes to the previously reported inhibitory effect of topical latanoprost on myopia progression in young guinea pigs warrants investigation.

Using image data to numerically correct the jitter in polarization depth encoding PS-OCT.

In swept source polarization depth encoding polarization sensitive optical coherence tomography (PS-OCT), the laser jitter induces additional noise to the polarization sensitive measurement. In this Letter, we developed a numerical algorithm to correct the jitter phases based on the image data using the Mueller matrix calculus. The algorithm was demonstrated on in vivo retina imaging of a guinea pig with a custom-built PS-OCT system. The performance of the proposed algorithm was almost comparable to the conventional method of using a physical calibration signal. By not requiring a hardware generated calibration signal and k-clock, the proposed algorithm is useful to reduce the complexity and the cost of a polarization depth encoding PS-OCT system.

Kaempferol Prevents Against Ang II-induced Cardiac Remodeling Through Attenuating Ang II-induced Inflammation and Oxidative Stress.

Heart failure characterized by cardiac remodeling is a global problem. Angiotensin II (Ang II) induces cardiac inflammation and oxidative stress, which also is implicated in the pathophysiology of adverse collagen accumulation-induced remodeling. Kaempferol (KPF), a kind of flavonoid compounds, is capable of anti-inflammatory and antioxidant activities. However, the target of KPF still remains blurred. In this study, we investigated the effect of KPF on Ang II-induced collagen accumulation and explored the underlying mechanisms. Our results suggested that KPF prevented Ang II-induced cardiac fibrosis and dysfunction, in mice challenged with subcutaneous injection of Ang II. In culture cells, KPF significantly reduced Ang II-induced collagen accumulation. Furthermore, KPF remarkably decreased inflammation and oxidative stress in Ang II-stimulated cardiac fibroblasts by modulating NF-κB/mitogen-activated protein kinase and AMPK/Nrf2 pathways.

Schisandrin C targets Keap1 and attenuates oxidative stress by activating Nrf2 pathway in Ang II-challenged vascular endothelium.

Vascular endothelial dysfunction plays a crucial role in the pathogenesis of cardiovascular diseases. Oxidative stress is a key pathophysiological mechanism underpinning endothelial dysfunction. Schisandrin C (Sch C), a dibenzocyclooctadiene derivative of Schisandra chinensis, has antioxidative properties. Here, we report the use of Sch C as a novel therapeutic for the treatment of angiotensin II (Ang II)-induced endothelial deficits and explore the underlying mechanisms and the target of Sch C. Our results demonstrated that Sch C treatment prevents aorta oxidative stress and improves relaxation in mice, challenged with subcutaneous infusion of Ang II. In addition, Sch C significantly ameliorates Ang II-induced oxidative stress in rat aortic endothelial cells. We then discovered that these antioxidative effects of Sch C are mediated through the induction of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Using an expression plasmid and molecular docking, we identified that Kelch-like ECH-associated protein-1 (Keap1), a negative regulator of Nrf2, is a target of Sch C. These findings provide evidence for the potential use of Sch C as an antioxidative agent for treatment of vascular endothelial deficits.

[Age distribution characteristics of intestinal segmented filamentous bacteria and their relationship with intestinal mucosal immunity in children].

OBJECTIVE: To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity. METHODS: The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry. RESULTS: The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age: the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P<0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P<0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P<0.05). CONCLUSIONS: Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.

Inhibition of Epidermal Growth Factor Receptor (EGFR) Reduces Lipopolysaccharide (LPS)-Induced Activation and Inflammatory Cytokines in Hepatic Stellate Cells In Vitro.

BACKGROUND Epidermal growth factor receptor (EGFR) expression is associated with hepatic fibrogenesis. Activated hepatic stellate cells (HSCs) release inflammatory cytokines and extracellular matrix (ECM). The aim of this in vitro study was to investigate HSCs, activated by lipopolysaccharide (LPS), and the role of EGFR using the small molecule EGFR inhibitor, AG1478, and using knockdown of the EGFR gene using small interfering RNA (siRNA) cell transfection. MATERIAL AND METHODS HSCs, isolated from male Sprague-Dawley rats, were cultured and treated with and without LPS (100 ng/mL), with and without AG1478 (2.5 µM and 5.0 µM) Cell survival and proliferation were studied using an MTT assay. Western blot was used to measure levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IκBα, cytoplasm and nuclear NFκB and EGFR in the cell lysates before and after small interfering RNA (siRNA) transfection. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of transforming growth factor (TGF)-ß, Col-1, and α-smooth muscle actin (SMA). The Toll-like receptor 4 (TLR4) antagonist TAK-242 and the selective c-Src inhibitor, PP2 in LPS induced-EGFR phosphorylation was evaluated using Western blot. RESULTS Inhibition of EGFR decreased LPS-induced HSC proliferation and inflammatory cytokines. The TLR4 antagonist TAK-242, and the c-Src inhibitor, PP2 reduced EGFR activation of HSCs, indicating a possible role for the TLR4/c-Src signaling cascade in LPS-induced HSC activation. CONCLUSIONS Activation of HSCs by LPS in vitro, including the expression of inflammatory cytokines and mediators of fibrogenesis, were shown to be dependent on the expression of EGFR.

Myocardial Infarction in a Young Man With Nephrotic Syndrome.

A 26-year-old man diagnosed with nephrotic syndrome (NS) 2 years previously presented with chest pain. An electrocardiogram (ECG) performed at a local hospital showed ST-elevation in chest leads. Cardiac troponin-I was significantly positive. Echocardiography revealed mild regional wall-motion abnormalities in the heart apex. Seven days later, angiography (CAG) revealed a thrombus in the left anterior descending branch (LAD). Tirofiban was injected into the LAD for thromboclasis. ECG after CAG showed the ST-segment was much lower than before. The diagnosis after CAG was ST-segment elevation myocardial infarction (MI) and thrombogenesis in the LAD. He continued to receive antiplatelet and anticoagulation medication and atorvastatin after CAG, and was discharged 3 days later. MI is very rare in young males, but the incidence of MI is 8 times higher than normal in patients with NS. For young patients with MI, clinicians should pay more attention to the history of previous diseases with high risk of thromboembolism and they should actively promote prevention and the treatment of renal disease patients to reduce the incidence of complications of thromboembolism.

Dronedarone and Amiodarone Induce Dyslipidemia and Thyroid Dysfunction in Rats.

BACKGROUND/AIMS: Amiodarone, a thyroid hormone-like molecule, can induce dyslipidemia and thyroid dysfunction. However, the effects of dronedarone on lipid metabolism and of both dronedarone and amiodarone on thyroid function and lipid metabolism remain unknown. METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups (10 in each group): normal control (NC), amiodarone-treated (AMT), dronedarone-treated (DRT), rats treated with amiodarone combined with polyene phosphatidylcholine (AC), and rats treated with dronedarone combined with polyene phosphatidylcholine (DC). Rats were given amiodarone (120 mg/kg/d), dronedarone (120 mg/kg/d), and polyene phosphatidylcholine (200 mg/kg/d) for 13 weeks. At the end of weeks 4, 8, 12, and 13, plasma-free triiodothyronine (FT3), free thyroxine (FT4), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were determined. At the end of this protocol, rats were sacrificed and the thyroid glands were isolated, weighed, and examined histopathologically. The protein expression of Bcl-2 was measured by immunochemical staining. The mRNA expression of thyroglobulin (Tg), type-1 deiodinase (D1), and thyroid peroxidase (TPO) were detected by polymerase chain reaction (PCR). RESULTS: Compared with the NC group, FT3 and FT4 levels in the DRT and DC groups significantly increased at week 4 but declined thereafter. The AMT and AC groups had lower FT3 levels but comparable FT4 levels. The levels of TG, LDL-c, and HDL-c in the NC group were lower than those in the other groups whereas the LDL-c/HDL-c ratio was lowest in the AMT group. Bcl-2 expression significantly increased in the DRT group. The mRNA expression of Tg increased whereas the mRNA expression of D1 decreased. Dronedarone induced hyperthyroidism at the early stage and hypothyroidism at the late stage whereas amiodarone only caused hypothyroidism. CONCLUSION: Both dronedarone and amiodarone can induce dyslipidemia and increase the levels of TC, LDL-c, and HDL-c, and these effects may be associated with thyroid dysfunction.

Rh(II)/Brønsted acid cocatalyzed intramolecular trapping of ammonium ylides with enones: diastereoselective synthesis of 2,2,3-trisubstituted indolines.

Highly diastereoselective intramolecular trapping of ammonium ylides with enones has been developed through a Rh(II)/Brønsted acid cocatalytic strategy. This process allows rapid and efficient construction of N-unprotected polyfunctional 2,2,3-trisubstituted indolines in moderate to good yields with excellent diastereoselectivity.

Copper/N,N-dimethylglycine catalyzed goldberg reactions between aryl bromides and amides, aryl iodides and secondary acyclic amides.

An efficient and general copper-catalyzed Goldberg reaction at 90-110 °C between aryl bromides and amides providing the desired products in good to excellent yields has been developed using N,N-dimethylglycine as the ligand. The reaction is tolerant toward a wide range of amides and a variety of functional group substituted aryl bromides. In addition, hindered, unreactive aromatic and aliphatic secondary acyclic amides, known to be poor nucleophiles, are efficiently coupled with aryl iodides through this simple and cheap copper/N,N-dimethylglycine catalytic system.

[Timing of nasojejunal feeding tube placement and enteral nutrition in children with acute pancreatitis].

OBJECTIVE: To investigate the impact of timing of nasojejunal feeding tube placement and enteral nutrition on clinical outcomes in children with acute pancreatitis. METHODS: A retrospective analysis was performed on the clinical data of 31 children with acute pancreatitis, who received nasojejunal feeding between January 2008 and July 2013, to investigate the relationship of abdominal symptoms/signs and serum amylase level with the tolerability of catheterization and success rate of enteral nutrition. The treatment outcome and incidence of adverse reactions and complications were compared between the early enteral nutrition group ( ≤7 days from the onset of the disease) and late enteral nutrition group (>7 days from the onset of the disease). RESULTS: Abdominal symptoms/signs and serum amylase level were independent of the tolerable rate of catheterization and success rate of enteral nutrition. Compared with the late enteral nutrition group, the early enteral nutrition group had a shortened time to normal serum amylase level, significantly reduced incidence of systemic complications, length of hospital stay, and hospitalization expenses, and less weight gain. The tolerable rate of catheterization and success rate of enteral nutrition showed no significant difference between the two groups. Similarly, no significant differences were found in the increase in albumin level after enteral nutrition, duration of enteral nutrition, incidence of adverse reactions, and incidence of local complications. CONCLUSIONS: Abdominal symptoms/signs and serum amylase level cannot be used as a measure of whether nasojejunal feeding tube placement and enteral nutrition can be performed. Early enteral nutrition can better improve clinical outcomes in children with acute pancreatitis, and it is feasible.

Evaluation of the value of combined thyroid function-related indexes in the prognosis prediction of patients with differentiated thyroid cancer.

This study aims to evaluate the prognostic significance of thyroid function-related indices in patients with differentiated thyroid cancer (DTC). This retrospective analysis included 90 patients diagnosed with DTC and treated at our hospital from January 2010 to January 2019. Patients were classified into 2 groups based on whole-body imaging results: 67 with a favorable prognosis and 23 with a poor prognosis. The study compared clinical data and thyroid function indices between these groups to assess their efficacy in prognostic prediction. Patients in the poor prognosis group had a higher occurrence of T3-4 stage cancer (P = .006) and ≥2 lymph node metastases (P = .019). Notably, levels of total thyroxine (TT4), thyroid-stimulating hormone (TSH), and thyroglobulin antibody (Tg-Ab) were significantly elevated in this group (P < .001 for each). Receiver operating characteristic analysis revealed substantial predictive accuracy for TT4, TSH, and Tg-Ab (area under curve of 0.747, 0.820, and 0.720, respectively). The columnar graphical model used for prediction demonstrated a high concordance index (C-index = 0.919), superior to single-indicator evaluations. Thyroid function indices, specifically TT4, TSH, and Tg-Ab, play a crucial role in the prognostic assessment of patients with DTC. The column-line diagram model effectively enhances prophetic prediction, aiding in clinical decision-making.

Application of surface-enhanced Raman spectroscopy to human serum for diagnosing liver cancer.

This study investigates the application of surface-enhanced Raman spectroscopy (SERS) in the diagnosis of liver cancer using Ag@SiO2 nanoparticles as SERS substrates. A SERS test was conducted on serum samples obtained from patients with liver cancer and healthy individuals. After repeated several times experiments, it was found that the best SERS spectrum was obtained when the volume ratio of serum to deionized water was 1:2. Moreover, data preprocessing was performed on the tested SERS spectrum, and the preprocessed spectral data were combined with principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) for further analysis to classify the serum samples of patients with liver cancer and healthy individuals. The results showed that the classification effect of standard normal variate spectral data combined with the OPLS-DA was the best for the serum samples, with a classification accuracy of 97.98%, sensitivity of 97.14%, and specificity of 98.44%. Therefore, the SERS technology can be developed as a favorable method for the accurate diagnosis of liver cancer in the future.

Paeoniflorigenone inhibits ovarian cancer metastasis through targeting the MUC1/Wnt/ß­catenin pathway.

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial­mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit­8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S­phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/ß­catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/ß­catenin pathway to induce anti­metastatic, anti­invasive and anti­EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

Quantitative determination of carbosulfan residues by surface-enhanced Raman spectroscopy.

Carbosulfan gets easily decomposed into carbofuran and 3-Hydroxy carbofuran in vegetables and forms harmful residues. To detect the residues of carbosulfan in vegetables (for example, cowpeas), a super-sensitive method of surface-enhanced Raman spectroscopy (SERS) was used in this work. Silver sol was prepared as the SERS substrate. To solve the adsorption problem of carbosulfan on Ag nanoparticles, 2, 6-dichloroquinone-4-chlorimide (chromogenic agent), and sodium hydroxide were added in carbosulfan to generate a complex, which was then mixed with the silver sol in the best proportion to examine SERS spectra. According to density functional theory calculations, the spectral peak positions of carbosulfan were determined. The optimal mixing ratio of the complex and the silver sol to obtain the optimal SERS spectrum and the detection limit of carbosulfan were investigated. The ultra-sensitive detection of carbosulfan residues (8.7 × 10-11 g/L) in cowpeas was realized. The results of this work indicate that SERS is a promising technique for detecting single-molecule pesticide residues in vegetables.

Applications of Genomics and Transcriptomics in Precision Medicine for Myopia Control or Prevention.

Myopia is a globally emerging concern accompanied by multiple medical and socio-economic burdens with no well-established causal treatment to control thus far. The study of the genomics and transcriptomics of myopia treatment is crucial to delineate disease pathways and provide valuable insights for the design of precise and effective therapeutics. A strong understanding of altered biochemical pathways and underlying pathogenesis leading to myopia may facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures. In this review, we summarize current data about the genomics and transcriptomics of myopia in human and animal models. We also discuss the potential applicability of these findings to precision medicine for myopia treatment.

An anti-inflammatory chondroitin sulfate-poly(lactic-co-glycolic acid) composite electrospinning membrane for postoperative abdominal adhesion prevention.

Postoperative abdominal adhesion is a very common and serious complication, resulting in pain, intestinal obstruction and heavy economic burden. Post-injury inflammation that could activate the coagulation cascade and deposition of fibrin is a major cause of adhesion. Many physical barrier membranes are used to prevent abdominal adhesion, but their efficiency is limited due to the lack of anti-inflammatory activity. Here, an electrospinning membrane composed of poly(lactic-co-glycolic acid) (PLGA) providing support and mechanical strength and chondroitin sulfate (CS) conferring anti-inflammation activity is fabricated for preventing abdominal adhesion after injury. The PLGA/CS membrane shows a highly dense fiber network structure with improved hydrophilicity and good cytocompatibility. Importantly, the PLGA/CS membrane with a mass ratio of CS at 20% provides superior anti-adhesion efficiency over a native PLGA membrane and commercial poly(D, L-lactide) (PDLLA) film in abdominal adhesion trauma rat models. The mechanism is that the PLGA/CS membrane could alleviate the local inflammatory response as indicated by the promoted percentage of anti-inflammatory M2-type macrophages and decreased expression of pro-inflammatory factors, such as IL-1ß, TNF-α and IL-6, resulting in the suppression of the coagulation system and the activation of the fibrinolytic system. Furthermore, the deposition of fibrin at the abdominal wall was inhibited, and the damaged abdominal tissue was repaired with the treatment of the PLGA/CS membrane. Collectively, the PLGA/CS electrospinning membrane is a promising drug-/cytokine-free anti-inflammatory barrier for post-surgery abdominal adhesion prevention and a bioactive composite for tissue regeneration.

Posterior scleral birefringence measured by triple-input polarization-sensitive imaging as a biomarker of myopia progression.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

Effects of mid-myocardial pacing on transmural dispersion of repolarization and arrhythmogenesis.

INTRODUCTION: Epicardial (Epi) activation of the left ventricular (LV) wall increases transmural dispersion of repolarization (TDR), which creates a substrate for the development of ventricular arrhythmia. We hypothesize that pacing from the LV mid-myocardium may decrease the TDR and occurrence of arrhythmias. METHODS AND RESULTS: A transmural electrocardiogram and transmembrane action potentials were simultaneously recorded from Epi, mid-myocardial (M), and endocardial (Endo) layers of the arterially perfused canine LV wedge preparations (n= 8). Transmural dispersion of repolarization varied when the preparations were paced at each layer, respectively (Endo pacing, 35.6 ± 6.6 ms; M pacing, 34.9 ± 7.3 ms; Epi pacing, 72.4 ± 4.9 ms; P< 0.001). A significant difference was noted in TDR between M pacing and Epi pacing (P< 0.001), but not between M pacing and Endo pacing (P= 0.831). This result was reproducible in the presence of ischaemia-reperfusion experiments (n= 8). Transmural dispersion of repolarization was amplified as compared with non-ischaemic experiments and differed when preparations were paced at each layer (Endo pacing, 62.8 ± 13.8 ms; M pacing, 63.3 ± 13.3 ms; Epi pacing, 111.1 ± 17.7 ms; P< 0.001). There was again no significant difference between Endo pacing and M pacing (P= 0.948). However, as pacing was shifted from M to Epi, there was a significant increase in TDR (P< 0.001). Ventricular arrhythmias were induced in two of eight ischaemic preparations during Epi pacing, but did not occur in either M or Endo pacing. CONCLUSION: Mid-myocardial pacing can significantly decrease the TDR and prevent the occurrence of ventricular arrhythmias as compared with Epi pacing.

Copper-Catalyzed Multicomponent Reactions of Intramolecular and Intermolecular Thiotrifluoromethylation of Alkenes: Access to CF3-Containing 2-Iminothiazolidines and Isothioureas.

A copper-catalyzed multicomponent reaction of secondary amines bearing allyl substitution, isothiocyanates, and Togni reagent II has been developed under Cs2CO3 in DCE at 75 °C. An intermolecular multicomponent reaction of thioureas, activated and unactivated alkenes, and Togni reagent II has also been developed under DMAP in acetonitrile at room temperature. These two alkene difunctionalization reactions provide CF3-containing 2-iminothiazolindines and isothioureas in moderate to excellent yields with broad substrate scope and good functional group tolerance, respectively.