Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal.

OBJECTIVES: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high-risk patients with acute coronary syndromes (ACS). BACKGROUND: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. METHODS: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. RESULTS: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P=0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)-related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for >or=8 Fr (P<0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. CONCLUSIONS: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.     

Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis

The goal of this prospective study was to assess non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10–20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease. Trial registration number: DRKS00004940.     

P-glycoprotein function and expression during obstructive cholestasis in rats

OBJECTIVES: The present study was aimed at evaluation of in vivo biliary and renal excretion of rhodamine 123 (Rho123), a P-glycoprotein (P-gp) substrate, in rats during either acute or chronic cholestasis induced by bile duct obstruction (BDO). METHODS: The Rho123 clearance study was performed either one (BDO1) or seven (BDO7) days after BDO. Bile flow was reconstituted, and bile and urine were collected after steady-state plasma concentration of Rho123 was attained. Tissue expression of P-gp was evaluated by quantitative immunohistochemistry, and immunoblotting. RESULTS: Significant up-regulation of the liver P-gp protein was observed in acute and chronic cholestasis. Primary periportal location of P-gp was enlarged also to pericentral areas. In the kidneys, immunohistochemistry showed pancellular increase in P-gp after 1 day of BDO, which subsided after 7 days of BDO. Nevertheless, biliary and renal clearances (CL(Bile) and CL(R)) of Rho123 did not reflect the induction of P-gp expression. While CL(Bile) was reduced one day after cholestasis and restored on the seventh day, the CL(R) was preserved in BDO1 group and reduced in BDO7 group without change in glomerular filtration rate. In parallel, biliary and renal clearances of conjugated bilirubin were significantly reduced in both cholestatic groups compared with controls. CONCLUSION: These findings suggest that extrahepatic cholestasis causes time-dependent changes in elimination of Rho123 which do not exactly reflect alteration of P-gp expression in the rat liver and kidney. These data may help to explain impaired elimination of P-gp substrates after short-term cholestasis that may commonly occur in clinical practice.     

Recurrence of colorectal liver metastases after surgical treatment: multifactorial study

BACKGROUND/AIMS: The authors evaluated the significance of various factors regarding the recurrence of colorectal liver metastases (CLM) after liver resection or radiofrequency ablation. METHODOLOGY: 82 patients were operated on for CLM at our department between 1998 and 2003. Radical surgery was performed in 58 patients (74.4%), an palliative surgery in 20 (25.6%). Recurrence of the disease was recorded in 53 patients (71.6%), 21 (28.4%) were without any sign of recurrence. The factors examined in the multifactorial analysis were: age and sex, localization of the primary carcinoma, Dukes classification, grading, histology, microscopically free resection line, chemotherapy and radiotherapy after colorectal or liver surgery, different types of liver resection, radical versus palliative liver surgery, complication after liver surgery, laterality of metastatic process, number of metastases, blood transfusion, staging, repeated liver surgery. Long-rank and Wilcoxon test were used for the statistical evaluation. RESULTS: The factors statistically significant for disease-free interval after liver surgery were: unilaterality of metastatic process, microscopically free resection line, radical versus palliative surgical treatment. The survival rates after liver surgery and after the primary operation were dependent on grading, age, radical versus palliative resection, Dukes classification and staging. CONCLUSIONS: These factors could play an important role as predictors of colorectal cancer recurrence in patients' follow-up period after liver surgery for CLM.     

The effect of spousal mental and physical health on husbands' and wives' depressive symptoms, among older adults: longitudinal evidence from the Health and Retirement Survey

OBJECTIVE: To estimate the effect of spousal depressive symptoms and physical health on respondents' depressive symptoms in a national sample of older married couples. METHOD: We used data on 5,035 respondent husbands and wives from the 1992 and 1994 waves of the Health and Retirement Survey. Multivariate regression models were estimated to examine the impact of spousal depressive symptoms and physical health on respondents' depressive symptoms. RESULTS: Adjusting for respondent mental and physical health and sociodemographic traits, having a spouse with more depressive symptoms was associated with significantly higher follow-up depressive symptoms in the respondent (p < .001). Controlling for spousal depressive symptoms, a decline in the spouses' physical health was associated with a significant reduction in respondent depressive symptoms (p < .05). DISCUSSION: Our findings suggest that health care providers treating older adults should be sensitive to the possibility that spouses may be affected when clients suffer poor mental or physical health.     

Direct in situ observations of single Fe atom catalytic processes and anomalous diffusion at graphene edges

Single-atom catalysts are of great interest because of their high efficiency. In the case of chemically deposited sp² carbon, the implementation of a single transition metal atom for growth can provide crucial insight into the formation mechanisms of graphene and carbon nanotubes. This knowledge is particularly important if we are to overcome fabrication difficulties in these materials and fully take advantage of their distinct band structures and physical properties. In this work, we present atomically resolved transmission EM in situ investigations of single Fe atoms at graphene edges. Our in situ observations show individual iron atoms diffusing along an edge either removing or adding carbon atoms (viz., catalytic action). The experimental observations of the catalytic behavior of a single Fe atom are in excellent agreement with supporting theoretical studies. In addition, the kinetics of Fe atoms at graphene edges are shown to exhibit anomalous diffusion, which again, is in agreement with our theoretical investigations.Defects in graphene, including vacancies (1), dislocations (2), grain boundaries (3), and edges (4), are currently of interest, because they open up a variety of ways with which to tune the properties of pristine graphene. Dopant atoms in graphene are also of tremendous interest (e.g., transition metal atoms, which substitute carbon in graphene sheets, have theoretically been shown to have unusual magnetic or catalytic properties) (5). Single atoms or small clusters in graphene [e.g., N (6) and Fe (7–9)] have been directly observed with high-resolution transmission EM (TEM). Si dopant species have been directly observed with scanning TEM (10). In these cases, the atoms were embedded within the graphene. In addition, single Au (11, 12) and Al (12) atoms have also been observed (using TEM or scanning TEM) to be absorbed at the edges of graphene. The interactions between single metal atoms and graphene edges are complicated because of the different types of trapping states at the edges (11). In addition, some theoretical works suggest that the atomic configurations at graphene edges are greatly affected by nearby transition metal atoms (13–15).Here, we examine individual Fe atoms residing at graphene edges. Single metal atom catalysts have recently been proposed as a means to maximize catalytic efficiency (16, 17). Thus, atoms at graphene edges are of great interest for their catalytic potential, particularly to gain insight to the catalytic growth of sp² carbon (e.g., graphene) by transition metals. By means of low-voltage aberration-corrected TEM (LVACTEM) (18), the atomic configurations of an Fe atom at a graphene edge can be determined, and in addition, the dynamics of a single Fe atom can be recorded. Pentagon–hexagon transitions are observed and reveal the catalytic addition (growth) or removal processes. These processes are in excellent agreement with our ab initio and molecular dynamics (MD) simulations, which are also in agreement with a previously proposed catalytic growth model for carbon nanotubes (19). In addition, the kinetics of Fe atoms at graphene edges are shown to exhibit anomalous diffusion, which again, is in agreement with our theoretical investigations.Previous studies have shown that the 2D behavior of individual atoms over the basal plane in graphene exhibits Brownian motion. From this information, the 2D diffusion coefficient as well as the average Arrhenius activation energy could be extracted (20, 21). The spatial probability of a particle in Brownian motion follows a Gaussian distribution. In this case, the mean square displacement [MSD; <R²(t)>] is dependent linearly with respect to time, and the gradient corresponds to the diffusion coefficient (D) and is written as <R²(t)> = 2nDt (where n is dimensionality) (22, 23). Similar to previous observations of an Au atom at graphene edges (11), our in-depth experimental observations reveal that the diffusion of a single (Fe) atom along the edge of single-layer graphene is directly related to the atomic configuration of the graphene edge. Moreover, the random 1D diffusion of an Fe atom along a graphene edge does not follow Brownian motion but exhibits anomalous diffusion (namely, sub- or superdiffusion). Subdiffusion is attributed to the presence of trapping configurations. Without such trapping configurations, superdiffusion (levy flight) is obtained.Details on the preparation and transfer method of the chemical vapor deposition-grown graphene specimens used in this work can be found elsewhere in the literature (24–26) and SI Appendix. The transferred synthetic graphene is found to occasionally have holes, which can be augmented on electron beam irradiation in a low-voltage C_s aberration-corrected transmission electron microscope (80 kV acceleration voltage). These freshly in situ-derived edges from the augmented holes provide a clean [previous electron energy loss spectrum and TEM study confirmed no oxygen or nitrogen species on these edges (27) as well as no hydrogen (28)] and convenient platform to study the 1D motion of adsorbed Fe atoms. Because of the larger binding energy of an Fe atom at graphene open edges as opposed to binding at the basal plane, Fe atoms tend to reside at the edges. The Fe atoms are present as remnants from the transfer process, in which FeCl₃ was used as an etchant to remove the underlying Ni–Mo over which the graphene was synthesized. Our electron energy loss spectrum studies previously confirmed that these atoms are Fe (26). In our in situ LVACTEM, the atoms are imaged with dark-contrast conditions to optimize imaging (29). The specific experimental condition can be found in Materials and Methods.     

The "robust yet fragile" nature of the Internet

The search for unifying properties of complex networks is popular, challenging, and important. For modeling approaches that focus on robustness and fragility as unifying concepts, the Internet is an especially attractive case study, mainly because its applications are ubiquitous and pervasive, and widely available exposition exists at every level of detail. Nevertheless, alternative approaches to modeling the Internet often make extremely different assumptions and derive opposite conclusions about fundamental properties of one and the same system. Fortunately, a detailed understanding of Internet technology combined with a unique ability to measure the network means that these differences can be understood thoroughly and resolved unambiguously. This article aims to make recent results of this process accessible beyond Internet specialists to the broader scientific community and to clarify several sources of basic methodological differences that are relevant beyond either the Internet or the two specific approaches focused on here (i.e., scale-free networks and highly optimized tolerance networks).     

The role of pain in the recovery of instrumental and social functioning after hip fracture

OBJECTIVE: It is critical to identify modifiable factors associated with functional recovery from hip fracture. The authors examined the association between pain intensity and two functional endpoints-instrumental activities of daily living and social activity participation-after hip fracture. METHOD: A total of 270 cognitively intact, community-dwelling persons older than 65 who underwent surgical hip fracture repair in New Haven, Connecticut, were followed for 12 months. RESULTS: Pain intensity was strongly negatively associated with both instrumental and social functioning (p values < .001). Increases in pain intensity between 6 and 12 months were also associated with concurrent decreases in function (p values < .001). These relationships were partly explained by depressive symptoms and a marker of physical ability-gait speed. DISCUSSION: Interventions to control pain may enhance functional status after hip fracture; however, pain relief must be maintained to sustain recovery. Attention to the complex relationships among pain, depressive symptoms, and physical impairments should inform intervention development.     

Discovery of new inhibitors of aldo-keto reductase 1C1 by structure-based virtual screening

Aldo-keto reductase 1C1 is a hydroxysteroid dehydrogenase that inactivates progesterone by converting it to 20alpha-hydroxyprogesterone. It also inactivates 3alpha,5alpha-tetrahydroprogesterone, an allosteric modulator of the gamma-aminobutyric acid receptor that has anaesthetic, analgesic, anxiolytic and anti-convulsant effects. Inhibitors of aldo-keto reductase 1C1 are thus very interesting as potential agents for the treatment of endometrial cancer, premenstrual syndrome, catamenial epilepsy, and depressive disorders, and for the maintenance of pregnancy. We have used the molecular docking program eHiTS for virtual screening of 1990 compounds from the National Cancer Institute "Diversity Set". Fifty compounds with the highest predicted binding energies were then evaluated in vitro. Three structurally diverse hits were obtained that inhibit aldo-keto reductase 1C1 in the low micromolar range of IC(50) values. These hits represent promising starting points for structural optimization in hit-to-lead development.     

The role of capsule endoscopy in obscure gastrointestinal bleeding

Background and study aimObscure gastrointestinal bleeding is mostly recurrent and originates in the small bowel, which can be only partially examined by conventional endoscopy. Capsule endoscopy has revolutionized the evaluation of obscure gastrointestinal bleeding (OGIB). The diagnostic yield of capsule endoscopy in OGIB was a main concern of many studies. The aim of this study is to assess the diagnostic yield of capsule endoscopy in cases of OGIB. Capsule-related complications and degree of inter-observer variation will be recorded as well.Patients and methods54 consecutive patients suffering from OGIB, whether occult or overt, were subjected to capsule examination and data analysis.ResultsThe majority (74.1%) presented with obscure overt bleeding. Examination was complete in 68.4%. The commonest lesions were angiodysplasias (17.5%). Examinations were negative for lesions in 35.1% and hampered by limitations in 19.3%. The capsule diagnostic yield was 56.1%, while capsule retention occurred in 3.5%. The inter-observer agreement for the cause of bleeding was 91.2%.ConclusionsCapsule endoscopy proved helpful in solving the mystery of OGIB. It succeeded in diagnosing the cause of bleeding and directing further management with good compliance, high proportion of inter-observer agreement and low incidence of complications.