Spectroscopy 21 (2007) 193-204 193 IOS Press Molecular dynamics in calf-thymus DNA, at neutral and low pH, in the presence of Na + , Ca 2+ and Mg 2+ ions: A Raman microspectroscopic study

Abstract. In this paper the Raman total half bandwidths of calf-thymus DNA vibrations have been measured as a function of pH, monovalent and divalent cations' type and concentration. The dependence of different band parameters on DNA molecular subgroup structure, on pH and on Na + , Ca 2+ and Mg 2+ ions concentrations, respectively, are reported. It is shown that changes in (sub)picosecond dynamics of molecular subgroups in calf-thymus DNA can be monitored with confocal Raman microspectroscopy. The half bandwidths and the global relaxation times for the vibrations at 728 cm (PO 2 − ), 1377 cm −1 (dA, dG, dT, dC), 1488 cm −1 (dG, dA) and 1580 cm −1 (dG, dA) of calf-thymus DNA are presented. The full-widths at half-height (FWHH) of the bands in calf-thymus DNA are typically in the wavenumber range from 7.4 to 31 cm −1 . The bandwidths in the Raman spectra are sensitive to a dynamics active on a time scale from 0.34 to 1.44 ps. Low pH-induced melting of double helical structure in calf-thymus DNA results for some bands in shorter global relaxation times, as a consequence of the increased interaction of the base moieties with the solvent molecules. The molecular dynamics characterizing the 785, 1094, 1377 and 1580 cm −1 vibrations, is faster in the case of high divalent cations DNA sample (pH 7), as compared to the respective low divalent cations DNA sample (pH 7), for both Ca 2+ and Mg 2+ ions. The vibrational energy transfer process of the guanine band at 1488 cm −1 is slower for the high salt DNA sample, pH 7 as compared to the corresponding low salt DNA sample, pH 7, for both Ca 2+ and Mg 2+ . Molecular dynamics characterizing the vibration at 1488 cm −1 is faster for DNA sample at high Na + ions (pH 7), as compared to the DNA sample at low Na + ions (pH 7). As far as the CaDNA and MgDNA complexes are concerned (pH 7), the global relaxation times of some base vibrations decrease for the case of magnesium ions, as compared to the case of the same concentration of calcium ions. The different ionic radius of the two types of metal cations (0.72 Å for Mg and 0.99 Å for Ca) were considered in explaining these results. Molecular relaxation processes of DNA subgroups, upon lowering the pH, in the presence of Na + , Ca 2+ and Mg 2+ ions are presented. Particularly, at low Ca 2+ concentration, upon lowering the pH, the molecular dynamics of DNA subgroups corresponding to vibrations at 728, 1376, 1488 and 1580 cm −1 is much faster, probably due to the denaturation process of the double helical DNA

Toward microfluidic SERS and EC-SERS applications via tunable gold films over nanospheres

Many promising applications of surface-enhanced Raman scattering (SERS), such as microfluidic SERS and electrochemical (EC)-SERS, require immersion of plasmonic nanostructured films in aqueous media. Correlational investigations of the optical response and SERS efficiency of solid SERS substrates immersed in water are absent in the literature. This work presents an approach for tuning the efficiency of gold films over nanospheres (AuFoN) as SERS substrates for applications in aqueous environment. AuFoN are fabricated by convective self-assembly of colloidal polystyrene nanospheres of various diameters (300–800 nm), followed by magnetron sputtering of gold films. The optical reflectance of the AuFoN and Finite-Difference Time-Domain simulations in both water and air reveal the dependence of the surface plasmon band on nanospheres’ diameter and environment. SERS enhancement of a common Raman reporter on AuFoN immersed in water is analyzed under 785 nm laser excitation, but also using the 633 nm line for the films in air. The provided correlations between the SERS efficiency and optical response in both air and water indicate the best structural parameters for high SERS efficiency and highlight a route for predicting and optimizing the SERS response of AuFoN in water based on the behavior in air, which is more practical. Finally, the AuFoN are successfully tested as electrodes for EC-SERS detection of the thiabendazole pesticide and as SERS substrates integrated in a flow-through microchannel format. The obtained results represent an important step toward the development of microfluidic EC-SERS devices for sensing applications.publishedVersio

Acute Viral Hepatitis A – Clinical, Laboratory and Epidemiological Characteristics

Background and Aims: Infection with hepatitis A virus is still one of the most common causes of hepatitis worldwide. The clinical manifestation of acute hepatitis A (AHA) in adults can vary greatly, ranging from asymptomatic infection to severe and fulminant hepatitis. The aim of this study was to describe the demographic, clinical characteristics, laboratory features and hospital outcome of adult patients with AHA over a consecutive period of 4 years within an area from Eastern European country. Methods: Two hundred and two adult patients diagnosed with AHA were retrospective, observational and analytic analized over a period of 4 years. Based on prothrombin time less than 50, the study group was stratified in medium (79.2%) and severe forms (20.8%). We investigated the clinical, laboratory and epidemiological features. Statistical analysis were applied to compare the medium and severe forms of AHA. Results: Most patients (72.7%) were younger than 40 years. The main symptoms included: dyspepsia (72.07%), jaundice (86.63%), asteno-adynamia (86.72%), and flu-like symptoms (53.46%). The hemorrhagic cutaneous-mucous manifestations (6.93%) associated with the severe forms of AHA (OR =12.19, 95%CI -3.59 - 41.3, p =0.001). We found statistically significant differences for PT (p <0.001), INR (p <0.001), TQ (p <0.001), ALAT (p <0.001), ASAT (p <0.001), ALP (p <0.001) and platelets (p =0.009) between severe and medium AHA forms. We found that TQ, INR, ALAT and ASAT have the highest diagnostic values, statistically significant (p <0.05 ) for severe AHA forms with AUC (0.99, 0.99, 0.72, 0.70) at values of sensitivity (95%, 90.5%, 89%, 95%) and specificity (98%, 99%, 88%,94%). Conclusions Medium severity AHA forms were found in most of the study group patients (79.2%). The severe AHA forms were associated with hemorrhagic cutaneous-mucous manifestations (OR =12.19, p =0.001). The univariate analysis proved a negatively statistically significant correlation between IP and ALAT, ASAT. The present study revealed that TQ, INR and ALAT have the highest diagnostic values and are statistically significant for severe AHA forms

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer

PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m(2) every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m(2) daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade >= 3 related treatment-emergent adverse events (TEAEs). The most common grade >= 3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication