Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation.

In thrombolytic therapy, plasminogen activators (PAs) are still the only group of drug approved to induce thrombolysis, and therefore, critical for treatment of arterial thromboembolism, such as stroke, in the acute phase. Functionalized nanocomposites have attracted great attention in achieving target thrombolysis due to favorable characteristics associated with the size, surface properties and targeting effects. Many PA-conjugated nanocomposites have been prepared and characterized, and some of them has been demonstrated with therapeutic efficacy in animal models. To facilitate future translation, this paper reviews recent progress of this area, especially focus on how to achieve reproducible thrombolysis efficacy in vivo.

Role of the anion in the underpotential deposition of cadmium on a Rh(111) electrode: probed by voltammetry and in situ scanning tunneling microscopy.

In situ scanning tunneling microscopy (STM) and cyclic voltammetry (CV) were employed to examine the underpotential deposition (UPD) of cadmium on a rhodium(111) electrode in sulfuric and hydrochloric acids. The (bi)sulfate and chloride anions in the electrolytes played a main role in controlling the number and arrangement of Cd adatoms. Deposition of Cd along with hydrogen adsorption occurred near 0.1 V (vs reversible hydrogen electrode) in either 0.05 M H2SO4 or 0.1 M HCl containing 1 mM Cd(ClO4)2. These coupled processes resulted in an erroneous coverage of Cd adatoms. The process of Cd deposition shifted positively to 0.3 V and thus separated from that of hydrogen in 0.05 M H2SO4 containing 0.5 M Cd2+. The amount of charge (80 microC/cm2) for Cd deposition in 0.5 M Cd2+ implied a coverage of 0.17 for the Cd adatoms, which agreed with in situ STM results. Regardless of [Cd2+], in situ STM imaging revealed a highly ordered Rh(111)-(6 x 6)-6Cd + HSO4- or SO42- structure in sulfuric acid,. In hydrochloric acid, in situ STM discerned a (2 x 2)-Cd + Cl structure at potentials where Cd deposition commenced. STM atomic resolution showed roughly one-quarter of a monolayer of Cd adatoms were deposited, ca. 50% more than in sulfuric acid. Dynamic in situ STM imaging showed potential dependent, reversible transformations between the (6 x 6) Cd adlattices and (square root 3 x square root 7)-(bi)sulfate structure, and between (2 x 2) and (square root 7 x square root 7)R19.1 degrees -Cl structures. The fact that different Cd structures observed in H2SO4 and HCl entailed the involvement of anions in Cd deposition, i.e. (bi)sulfate and chloride anions were codeposited with Cd adatoms on Rh(111).

Extranodal natural killer/T-cell lymphoma nasal type: detection by computed tomography features.

OBJECTIVES/HYPOTHESIS: Nasal natural killer/T-cell lymphoma (NKTL) often has an infiltrative pattern in computed tomography that makes them difficult to distinguish from benign inflammatory diseases. This study aimed to design a method of measuring the thickness of the nasal floor and nasal septum, determine the critical value of mucosal thickness that may implicate these NKTL cases from benign inflammatory disease, and finally make a complete flowchart to detect NKTL with minimal mistake. STUDY DESIGN: Thirty-two patients with nasal NKTL and 173 patients with severe chronic rhinosinusitis with or without polyposis were enrolled. The patients' data were collected retrospectively. METHODS: All patients underwent standard computed tomography of the paranasal sinuses. The coronal section near the vertical part of the ground lamina was chosen for measurement, and the thickest points along the nasal floor and septum were measured. RESULTS: Patients with NKTL had thicker nasal floors and/or septa than those with chronic rhinosinusitis, recurrent sinusitis, or pansinusitis (P < .001). If the cutoff points of the nasal floor and nasal septum thickness were set at 2.0 mm and 2.5 mm, respectively, the probability of being thicker than the corresponding points in the CRS group was <2%, and the possibility of other diagnoses should be considered. CONCLUSIONS: Nasal floor mucosal thickness >2.0 mm or nasal septum mucosal thickness >2.5 mm may be indicators serving as one of several important hints for implicit NKTL. Finally, we established a diagnostic flowchart to include all of these important hints. LEVEL OF EVIDENCE: 4.

Extranodal natural killer/T-cell lymphoma, nasal type: clinical and computed tomography findings in the head and neck region.

OBJECTIVES/HYPOTHESIS: In patients with nasal natural killer/T-cell lymphoma (NKTL), it is commonly without an obvious mass found in the nasal cavity by clinical or computed tomography (CT) findings. As a result, it takes longer to make a definite diagnosis when compared with other nasal malignancy. This study was designed to investigate clinical and CT findings of nasal NKTL. STUDY DESIGN: Forty-three patients with nasal NKTL were enrolled. The patients' data were collected retrospectively. METHODS: All patients underwent contrast-enhanced CT scans and endoscopic examinations. Symptoms were noted and recorded in detail. RESULTS: Patients with lymphoma limited to their nasal cavity or paranasal sinus (N/PN) presented symptoms similar to chronic rhinosinusitis, such as nasal obstruction and purulent nasal discharge. Patients with lymphoma of the nasopharynx or oropharynx (NPx/OPx) tended to present more frequently with epistaxis or blood-tinged sputum. On CT, NKTL was usually nonenhanced (79.1%), homogenous (100%), unilateral (61.9%), infiltrative (67.4%), and without central necrosis. Only 30.2% of the patients presented with a prominent mass. One disease-specific sign, different from patients with chronic rhinosinusitis, was that the mucosa of the nasal cavity was thickened without involvement of the mucosa of the paranasal sinus (40.6%). CONCLUSIONS: The thickening of the mucosa of the nasal cavity without similar involvement of the paranasal sinuses is easily overlooked in patients with NKTL. In addition, the imaging findings of thickened mucosa of the nasal floor and/or nasal septum near the inferior meatus, a prominent mass, and bony destruction should raise suspicion of this diagnosis.

A retrospective study on the long-term placement of peripherally inserted central catheters and the importance of nursing care and education.

BACKGROUND: Peripherally inserted central catheters (PICCs) have been used for years in Taiwan, but their broad usage has been restricted by their short durability and complications. OBJECTIVE: The aim of this study was to evaluate the most important factors causing failure of PICCs by comparing 2 periods of retrospectively studied cases before and after we implemented nursing care improvements. METHODS: We analyzed possible factors affecting the length of the insertion period, according to the reasons for catheter withdrawal after insertion, self-care ability, coagulation status, and other factors. We reviewed 2 different periods of PICC insertions at our hospital (133 and 143 cases, respectively) before and after an announcement of nursing educational comprehensive guidelines for post-PICC care. RESULTS: In the first period, the most common complication due to PICC placement was wound oozing (24.7%), followed by infection/phlebitis (9.7%), occlusion (6.7%), and leaking (3.8%). In the second period, comprehensive educational guidelines for post-PICC manipulation were provided. The outcomes of PICC insertions significantly improved from 33.8% in the first period to 64.3% in the second period (odds ratio, 3.53), and the complication rates of persistent oozing (7%), infection (4.2%), and occlusion (2.8%) significantly decreased. CONCLUSIONS: Changes in nursing care provided in the period 2 contributed to improvements in the success rate of PICC. IMPLICATIONS FOR PRACTICE: This is the first study suggesting that cancer nursing practice for PICC could benefit from professional guidelines that reinforce in-service education, strict control of PICC candidates without risk of coagulopathies, and a special nursing care system for patients with poor self-care ability.

Role stress and job satisfaction for nurse specialists.

AIM: This paper is a report of a study to illustrate the unique relationship between role stress and job satisfaction and provide recommendations for advanced nursing practice in Taiwan. BACKGROUND: International literature has shown that work role-related stress experienced by staff nurses predicts role strain, which in turn influences job satisfaction and intention to leave the job. In this study, the direct relationship between role stress and job satisfaction of nurse specialists was examined after controlling for personality trait and personal characteristics. METHOD: In 2004 a convenience sample of 129 nurse specialists from five acute care teaching hospitals in Taiwan participated. They completed a questionnaire (response rate 81%) focusing on personal characteristics, the Five Factor Model of personality traits, role stress (i.e. ambiguity, conflict, overload, incompetence) and job satisfaction (i.e. professionalism, interaction, demand/reward, control/recognition). Data were analysed using hierarchical regression models. RESULTS: After controlling for personality traits and personal characteristics, role stress variables predicted 24.8% of the variance in job satisfaction. Role ambiguity (P < 0.001) and role overload (P < 0.01) were the best predictors, but role conflict was not statistically significant. Role stress explained statistically significant proportions of the variance for each component of job satisfaction: professionalism (10.6%), interaction (16.7%), demand/reward (27.1%) and control/recognition (18.5%). Role ambiguity predicted all four satisfaction components, role overload predicted demand/reward and role incompetence predicted interaction. CONCLUSION: Organizational restructuring and administrative support are recommended to address the issues raised. Appropriate training, sufficient communications and supportive legislation are required. Future research should be conducted to evaluate the impact of these interventions.

Ordered molecular assemblies of substituted bis(phthalocyaninato) rare earth complexes on Au(111): in situ scanning tunneling microscopy and electrochemical studies.

Substituted bis(phthalocyaninato) rare earth complexes ML2 (M = Y and Ce; L = [Pc(OC8H17)8]2, where Pc = phthalocyaninato) were adsorbed onto single crystalline Au(111) electrodes from benzene saturated with either YL2 or CeL2 complex at room temperature. In situ scanning tunneling microscopy (STM) and cyclic voltammetry (CV) were used to examine the structures and the redox reactions of these admolecules on Au(111) electrodes in 0.1 mol dm(-3) HClO4. The CVs obtained with YL2- and CeL2-coated Au(111) electrodes respectively contained two and three pairs of redox peaks between 0 and 1.0 V (versus reversible hydrogen electrode). STM molecular resolution revealed that YL2 and CeL2 admolecules were imaged as spherical protrusions separated by 2.3 nm, which suggests that they were oriented with their molecular planes parallel to the unreconstructed Au(111)-(1 x 1). Both molecules when adsorbing from approximately micromolar benzene dosing solutions produced mainly ordered arrays characterized as (8 x 5 radical3)rect (theta = 0.0125). The redox reactions occurring between 0.2 and 1.0 V caused no change in the adlayer, but they were desorbed or oxidized at the negative and positive potential limits. The processes of adsorption and desorption at the negative potentials were reversible to the modulation of potential. Electrochemical impedance spectroscopy (EIS) and CV measurements showed that YL2 and CeL2 adlayers could block the adsorption of perchlorate anions and mediating electron transfer at the Au(111) electrode, leading to the enhancement of charge transfer for the ferro/ferricyanide redox couple.

In situ scanning tunneling microscopy of 1,6-hexanedithiol, 1,9-nonanedithiol, 1,2-benzenedithiol, and 1,3-benzenedithiol adsorbed on pt(111) electrodes.

Cyclic voltammetry (CV) and in situ scanning tunneling microscopy (STM) were used to examine four dithiol molecules, including 1,6-hexanedithiol, 1,9-nonanedithiol, 1,2-benzenedithiol, and 1,3-benzenedithiol, adsorbed on well-ordered Pt(111) electrodes in 0.1 M HClO(4). The open-circuit potential (OCP) of Pt(111) electrodes decreased substantially from 0.95 to 0.3 V (versus reversible hydrogen electrode) upon the adsorption of dithol molecules, which indicates that these adsorbates injected electrons into the Pt electrode. For all dithiol molecules, ordered adlattices of p(2 x 2) and (square root 3 x square root 3)R30 degrees were formed when the dosing concentration was lower than 150 microM and the potential of Pt(111) was more negative than 0.5 V. Raising the potential of Pt(111) from 0.1 to 0.4 V or more positive values could transform p(2 x 2) to (square root 3 x square root 3)R30 degrees before it turned disarray. The insensitivity of the structure of dithiol adlayers with their chemical structures was explained by upright molecular orientation with the formation of one Pt-S bond per dithiol molecule. This molecular orientation was independent of the coverage of dithiol molecules, as nucleation seeds produced at the beginning of adsorption were also constructed with p(2 x 2). The triangular-shaped STM molecular resolution suggested 3-fold binding of sulfur headgroup on Pt(111). All dithiols were adsorbed so strongly on Pt(111) electrodes that switching the potential negatively to the onset of hydrogen evolution in 0.1 M HClO(4) or water reduction in 1 M KOH could not displace dithiol admolecules.

In-situ scanning tunneling microscopy of carbon monoxide adsorbed on Au(111) electrode.

In-situ scanning tunneling microscopy (STM) coupled with cyclic voltammetry was used to examine the adsorption of carbon monoxide (CO) molecules on an ordered Au(111) electrode in 0.1 M HClO4. Molecular resolution STM revealed the formation of several commensurate CO adlattices, but the (9 x radical 3) structure eventually prevailed with time. The CO adlayer was completely electrooxidized to CO2 at 0.9 V versus RHE in CO-free 0.1 M HClO(4), as indicated by a broad and irreversible anodic peak which appeared at this potential in a positive potential sweep from 0.05 to 1.6 V. A maximal coverage of 0.3 was estimated for CO admolecules from the amount of charge involved in this feature. Real-time in-situ STM imaging allowed direct visualization of the adsorption process of CO on Au(111) at 0.1 V, showing the lifting of (radical 3 x 22) reconstruction of Au(111) and the formation of ordered CO adlattices. The (9 x radical 3) structure observed in CO-saturated perchloric acid has a coverage of 0.28, which is approximately equal to that determined from coulometry. Switching the potential from 0.1 to -0.1 V restored the reconstructed Au(111) with no change in the (9 x radical 3)-CO adlattice. However, the reconstructed Au(111) featured a pairwise corrugation pattern with two nearest pairs separated by 74 +/- 1 A, corresponding to a 14% increase from the ideal value of 65.6 A known for the ( radical 3 x 22) reconstruction. Molecular resolution STM further revealed that protrusions resulting from CO admolecules in the (9 x radical 3) structure exhibited distinctly different corrugation heights, suggesting that the CO molecules resided at different sites on Au(111). This ordered structure predominated in the potential range between 0.1 and 0.7 V; however, it was converted into new structures of (7 x radical 7) and ( radical 43 x 2 radical 13) on the unreconstructed Au(111) when the potential was held at 0.8 V for ca. 60 min. The coverage of CO adlayer decreased accordingly from 0.28 to 0.13 before it was completely removed from the Au(111) surface at more positive potentials.

Adsorption of formaldehyde on Pt(111) and Pt(100) electrodes: cyclic voltammetry and scanning tunneling microscopy.

The adsorption of formaldehyde (HCHO) on Pt(111) and Pt(100) electrodes was examined by cyclic voltammetry (CV) and in situ scanning tunneling microscopy (STM) in 0.1 M HClO(4). The extent of HCHO adsorption at both Pt electrodes was evaluated by comparing the CVs, particularly for the hydrogen adsorption and desorption between 0.05 and 0.4 V, obtained in 0.1 M HClO(4) with and without HCHO. The adsorption of HCHO on these Pt electrodes was significant only when [HCHO] >/= 10 mM. Adsorbed organic intermediate species acted as poisons, blocking Pt surfaces and causing delays in the oxidation of HCHO. Compared to Pt(111), Pt(100) was more prone to poisoning, as indicated by a 200 mV positive shift of the onset of HCHO oxidation. However, Pt(100) exhibited an activity 3 times higher than that of Pt(111), as indicated by the difference in peak current density of HCHO oxidation. Molecular resolution STM revealed highly ordered structures of Pt(111)-( radical7 x radical7)R19.1 degrees and Pt(100)-( radical2 x radical2) in the potential region between 0.1 and 0.3 V. Voltammetric measurements further showed that the organic poisons produced by HCHO adsorption behaved differently from the intentionally dosed CO admolecules, which supports the assumption for the formation of HCO or COH adspecies, rather than CO, as the poison. On both Pt electrodes, HCHO oxidation commenced preferentially at step sites at the onset potential of this reaction, but it occurred uniformly at the peak potentials.

Scanning tunneling microscopy of sulfur and benzenethiol chemisorbed on Ru(0001) in 0.1 M HClO4.

In situ scanning tunneling microscopy (STM) combined with linear sweep voltammetry was used to examine spatial structures of sulfur adatoms (SA) and benzenethiol (BT) molecules adsorbed on an ordered Ru(0001) electrode in 0.1 M HClO4. The Ru(0001) surface, prepared by mechanical polishing and electrochemical reduction at -1.5 V (vs RHE) in 0.1 M HClO4, contained atomically flat terraces with an average width of 20 nm. Cyclic voltammograms obtained with an as-prepared Ru(0001) electrode in 0.1 M HClO4 showed characteristics nearly identical to those of Ru(0001) treated in high vacuum. High-quality STM images were obtained for SA and BT to determine their spatial structures as a function of potential. The structure of the SA adlayer changed from (2 x mean square root of 3)rect to domain walls to (mean square root of 7 x mean square root of 7)R19.1 degrees and then to disordered as the potential was scanned from 0.3 to 0.6 V. In contrast, molecules of BT were arranged in (2 x mean square root of 3)rect between 0.1 and 0.4 V, while they were disordered at all other potentials. Adsorption of BT molecules was predominantly through the sulfur headgroup. Sulfur adatoms and adsorbed BT molecules were stable against anodic polarization up to 1.0 V (vs RHE). These two species were adsorbed so strongly that their desorption did not occur even at the onset potential for the reduction of water in 0.1 M KOH.

Elucidation of the deposition processes and spatial structures of alkanethiol and arylthiol molecules adsorbed on Pt111 electrodes with in situ scanning tunneling microscopy.

In situ scanning tunneling microscopy (STM) was used to examine the spatial structures of n-alkane thiols (1-hexanethiol, 1-nonanethiol, and 1-octahexanethiol) and arylthiols (benzenethiol and 4-hydroxybenzenethiol) adsorbed on well-ordered Pt111 electrodes in 0.1 M HClO4. The electrochemical potential and molecular flux were found to be the dominant factors in determining the growth mechanisms, final coverages, and spatial structures of these organic adlayers. Depending on the concentrations of the thiols, deposition of self-assembled monolayers (SAMs) followed either the nucleation-and-growth mechanism or the random fill-in mechanism. Low and high thiol concentrations respectively produced two ordered structures, (2 x 2) and (square root of 3 x square root of 3)R30 degrees , between 0.05 and 0.3 V. On average, an ordered domain spanned 500 A when the SAMs were made at 0.15 V, but this dimension shrank substantially once the potential was raised above 0.3 V. This potential-induced order-to-disorder phase transition resulted from a continuous deposition of thiols, preferentially at domain boundaries of (square root of 3 x square root of 3 x )R30 degrees arrays. All molecular adlayers were completely disordered by 0.6 V, and this restructuring event was irreversible with potential modulation. Since all thiols were arranged in a manner similar to that adopted by sulfur adatoms (Sung et al. J. Am. Chem. Soc. 1997, 119, 194), it is likely that they were adsorbed mainly through their sulfur headgroups in a tilted configuration, irrespective of the coverage. Both the sulfur and phenyl groups of benzenethiol admolecules gave rise to features with different corrugation heights in the molecular-resolution STM images. All thiols were adsorbed strongly enough that they remained intact at a potential as negative as -1.0 V in 0.1 M KOH.