Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Child and youth participatory interventions for addressing lifestyle-related childhood obesity: a systematic review.

A growing number of childhood obesity interventions involve children and youth in participatory roles, but these types of interventions have not been systematically reviewed. We aimed to identify child and youth participatory interventions in the peer-reviewed literature in order to characterize the approaches and examine their impact on obesity and obesity-related lifestyle behaviours. We searched PubMed/Medline, psychINFO and ERIC for quasi-experimental and randomized trials conducted from date of database initiation through May 2015 that engaged children or youth in implementing healthy eating, physical activity or weight management strategies. Eighteen studies met our eligibility criteria. Most (n = 14) trained youth to implement pre-defined strategies targeting their peers. A few (n = 4) assisted youth to plan and implement interventions that addressed environmental changes. Thirteen studies reported at least one statistically significant weight, physical activity or dietary change outcome. Participatory approaches have potential, but variation in strategies and outcomes leave questions unanswered about the mechanisms through which child and youth engagement impact childhood obesity. Future research should compare child-delivered or youth-delivered to adult-delivered health promotion interventions and more rigorously evaluate natural experiments that engage youth to implement environmental changes. With careful attention to theoretical frameworks, process and outcome measures, these studies could strengthen the effectiveness of child and youth participatory approaches.

Gustatory and olfactory dysfunction in older adults: a national probability study.

BACKGROUND: Olfactory and gustatory functions have not been well characterized in older adults in the US. Consequently, their relationships to sociodemographic characteristics, as well as physical and mental health, were studied in a large national probability sample using brief validated tests of chemosensory function. METHODS: A five-odour identification test and taste-impregnated strips of filter paper (sweet, sour, bitter, and salty) assessed the ability to identify chemosensory stimuli. RESULTS: Severe gustatory dysfunction was more prevalent than severe olfactory dysfunction. Age, education and sex were independently associated with performance on both the olfactory and gustatory identification tasks. Higher scores were associated with female sex, higher level of education, and lower age. Odour identification scores exhibited a positive, albeit weak, correlation with BMI, and food-related odours were better identified than non-food odours. In addition, odour identification performance was also negatively associated with depressive symptoms. CONCLUSIONS: These data demonstrate a high prevalence of severe gustatory and, to a somewhat lesser extent, olfactory dysfunction in a population-based sample and demonstrate that even brief tests are capable of detecting correlations between both chemical senses and relevant health measures outside a clinical setting.

Improving rates of cervical cancer screening and Pap smear follow-up for low-income women with limited health literacy.

Adult literacy is an independent and important predictor of health behavior. In 1993, the National Adult Literacy Survey conducted by the U.S. Department of Education demonstrated that one-third of the U.S. population over age 16 (44 million adults) is functionally illiterate. Several studies link low health literacy to self-reported poor health status, poor health behavior, and inadequate knowledge about disease. Epidemiologic studies of cancer prevention have not detected strong racial and ethnic disparities in disease detection and progression, resulting in an emphasis on behavioral and intervention-based research. Low literacy presents a wide-reaching barrier to disease prevention that, unlike race/ethnicity, is potentially modifiable. Here, we explore the relationship between health literacy and health behaviors related to cervical cancer prevention in an effort to address concerns about low rates of screening and follow-up in vulnerable populations. Our goal is to improve our understanding of the health impact of low literacy among urban women and to inspire interventions that will promote disease prevention behaviors in this population, particularly with regard to cervical cancer.

A structure-function study of nucleic acid-fluorenone complexes.

Several 2.7-bis-[(dialkylamino)-acetylamino]-fluoren-9-one derivatives (fluoramides) were synthesized as analogues of the DNA binding compound tilorone (2,7-bis[(diethylamino)-ethoxy]-fluoren-9-one). Previous studies showed the drugs to induce cytokines and inhibit reverse transcription. Here, their binding to DNA was evaluated using UV and circular dichroism studies. Like tilorone, the fluoramides derivatives also intercalate resulting in increased Tm values and new CD signatures. A preference to alternating A-T and G-C sequences was detected; only minor interaction to homologous sequences was observed. Moreover, no upper limit in the drug/DNA ratio was found, testing limit being the precipitation of the drug. However, surface plasmon resonance (SPR) studies of tilorone and 2,7-bis-[(dipropylamino)-acetyl-amino]-fluoren-9-one, indicate an astonishing drug/base pair ratio (r > 1), which point to a multitude of interactions under SPR conditions. Molecular modeling calculations, where the geometries of the complexes optimized under the assumption of intercalative and multitude of suprahelical arrangements, rationalize the observations. Based on the thermodynamic and biological studies, a structure-function model is proposed.

Self-assembly and lyomesophases formed by long-chain alkoxymethyl-nucleobase derivatives.

Amphiphilic complementary nucleobase derivatives, containing n-octadecyloxymethyl substituents at the N1 position of pyrimidine and N9 of purine, dissolved in chloroform form non-specific lyotropic mesophases, which were analyzed by optical polarizing microscopy. Molecular modeling studies visualize hypothetical horizontal and vertical nucleobase hydrogen-bonding and stacking arrangements, as well as aliphatic long-chain interstrand interaction.

Biomesogenic matrix systems.

The bifunctionally reactive nucleoside and distant nucleoside analogs adenosine (Ado), S-[(adenine-9-yl)methoxyethyl]-L-cysteine (Na-salt) (cysA) and 9-vinyladenine (vA) in aqueous solutions assemble on complementary polyuridylic acid templates to form complex lyomesophases. The systems are investigated by polarizing microscopy, differential scanning calorimetry (DSC) and 1H- and 31P-nmr spectroscopies, assisted by molecular modeling studies. The results indicate the importance of biomesogenic (pre)ordering in nucleic acid native and artificial matrix reactions.

Stabilization of Double Stranded Homologous Poly(dA)·Poly(dT) by Taxol.

Abstract The nucleic acid activity of taxol and paclitaxel was investigated with synthetic and natural oligo- and polynucleotides. The polynucleotides poly(dA)·poly(dT), poly(dG)·poly(dC), poly [d(A-T)]·poly[d(A-T)], poly[d(G-C)]·poly[d(G-C)] and calf thymus DNA were used. The oligonucleotides are 24-mers with d(purine)(24)·d(pyrimidine)(24) strands, as well as d[(purine)(x)-(pyrimidine)(x)]·d[(purine)(x)-(pyrimidine)(x)] sequences. The study was performed with spectroscopic and calorimetric methods in dilute and condensed DNA-solutions. In a recent study, taxol and paclitaxel showed molecular recognition of AT nucleotides with a high affinity to homologous (dA)·(dT) sequences; no interaction with GC nucleotides could be observed. An astonishing stabilization of the DNA duplex up to ΔT(m) = 25°C was measured by thermal denaturation with poly(dA)·poly(dT)/paclitaxel complexes. Circular dichroism signals of DNA (24-mer) containing homologous (dA)·(dT) tracts increased with increasing amount of the drug; for the other oligo- and polynucleotides no change in the spectra could be found. Contrary to this findings, circular dichroism (CD) spectra of poly(dA)·poly(dT)/paclitaxel complexes displayed reduced intensities of the signals at increasing drug concentrations. These findings in dilute solutions were complemented by differential scanning calorimetric investigations in condensed states (only calf thymus DNA tested). Increasing enthalpies by increasing amount of the drug point to a stabilization. Simple phosphate backbone interaction in the narrow groove of (dA)·(dT) tracts could be a sufficient explanation for all the results. Hydrophilic side groups of the drug interact with the phosphate and clip the strands together, while the hydrophobic parts of the molecule may disturb the polynucleobase formation.

A spectroscopic and thermodynamic study of Taxol nucleic acid complexes.

The interactions of natural and synthetic polynucleotide double strands with the antitumor agent paclitaxel and the oncological product "Taxol for Injection Concentrate" (abbreviated as taxol) were examined in diluted aqueous solutions by thermal denaturation profiles (Tm), CD spectra and UV-absorption measurements. Furthermore, DNA-paclitaxel and -taxol complexes in condensed nucleic acid solutions were studied by differential scanning calorimetry. As polynucleotides alternating and homologous poly[d(AT)] and poly[d(GC)] and calf thymus DNA were used. The results point to stabilizing interactions of paclitaxel to AT nucleotides, whereas in the presence of GC base pairings no interaction took place. Thereby the interaction to homologous (dA).(dT)-tracts seems to be preferred.

DNA-drug interaction measurements using surface plasmon resonance.

The interactions of the drugs 2,7-bis[(diethylamino)-ethoxy]-fluoren-9-one dihydrochloride (Tilorone), 2,7-bis[(dipropylamino)-acetamido]-fluoren-9-one dihydrochloride (FA-2), 2'-(4-hydroxyphenyl)-5-(4-methyl-1-piperazinyl)-2,5'-bi-1H-benzimidazole trihydrochloride (Hoechst 33258), and hematoporphyrin IX derivative (HPD) with synthetic self-complementary DNA (36-b.p.; 5'-biotin-spacer-[d(CGCTATATAGCG)]3-3') were studied by SPR (Surface Plasmon Resonance). Monolayers of biotinylated DNA were immobilized on a streptavidin-dextran-gold triple-layer. Small portions of the drugs (approximately 30 pmol/ml) were injected in continuous flow. The mass corresponded to the amount of the bound molecules. Injections of 50 mM sodium hydroxide pulses separated the DNA double strands, releasing the effector molecules. Subsequent treatments with the effectors gave reproducible results. The maximum interaction between drug and DNA was observed in the case of Tilorone. 41 molecules could bind to the 36-b.p. DNA duplex. To investigate the microscopic behavior in condensed nucleic acid phases, SFM (Scanning Force Microscopy)-imaging and polarizing microscopic observations of DNA-effector complexes were carried out. Supplementary UV-absorption thermal denaturation curves of DNA with the above-mentioned effectors in dilute solutions were measured. As an additional aid to understand the geometries of DNA-drug interactions, computer simulations were performed and compared with the experimental data.

A comprehensive resident training program in operative endoscopy.

We describe a structured and uniform resident experience in operative endoscopy and analyze the costs of implementing such a program at an urban academic medical center. The residency curriculum at Northwestern Memorial Hospital incorporates a five-part approach to endoscopy training: weekly endoscopy rounds, an annual animal laboratory for residents, an individual animal laboratory, supervision by skilled endoscopic surgeons, and a laparoscopic training facility. Thirty-two residents have completed the training over 4 years. The annual cost of the entire program is $34,500, which can be offset partially by vendor support. A comprehensive and continuous endoscopic training program is an important and affordable part of resident education.

High throughput grating VUV filter for the measurement of weak spectral lines in the presence of monochromatic background.

The design and characteristics of an optical filter using a holographic grating in combination with a multiple entrance and exit slit arrangement are described. The instrument transmits VUV radiation at Ar(I) 106.6 nm and Kr(I) 123.6 nm while excluding the hydrogen Lyman-alpha at 121.6 nm. The transmission at 123.6 nm is approximately 10%, if averaged over the circular entrance aperture of 28-mm diameter without correcting for the blocking by the masks. The corresponding transmission at 121.6 nm is 0.0001 or less. The concept with selective blocking of one wavelength and transmission at another using a multiple slit arrangement is transferable to any line pair. The 123.6-nm grating efficiency has been assessed as 37%.