Prognostic Risk Factors for the Development of Compartment Syndrome in Acute Lower Limb Ischemia Patients Treated With Catheter-Directed Thrombolysis.

BACKGROUND: To determine predisposing factors that may lead to the development of compartment syndrome (CS) in patients with acute lower limb ischemia (ALLI) managed with intra-arterial catheter-directed thrombolysis (CDT). METHODS: This is a retrospective study of patients admitted between 01/2002 and 12/2015 to three university hospitals in Tampere, Turku, and Oulu, Finland, with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb). Patients managed with CDT and aspiration thrombectomies (AT) as an adjunct to CDT were included in the study. Multivariable binary logistic regression models were used to detect possible risk factors for the development of CS and its impact on the limb salvage and survival. Amputation-free survival (AFS) rates of CS and non-CS patients were compared using Kaplan-Meier survival analysis. The length of hospitalization was calculated and compared between the CS and non-CS groups. RESULTS: A total of 292 CDTs with or without ATs were performed on patients with a mean age of 71 years (standard deviation 13 years), 151 (51.7%) being male. Altogether, 12/292 (4.1%) treatment-related CS cases were registered. Renal insufficiency (odds ratio [OR] 4.27, P = 0.07) was associated with an increased risk of CS. All CS cases were managed with fasciotomies. Treatment with fasciotomy was associated with a prolonged hospitalization of a median of 7 days versus the 4 days for non-CS patients, P < 0.001. During the median follow-up of 51 months (interquartile range 72 months), 152/292 (52.1%) patients died and 51/292 (17.5%) underwent major amputations. CS was not associated with an increased risk of mortality, but it was associated with a higher risk of major amputation (OR 3.87, P = 0.027). The AFS rates of patients with or without CS did not significantly differ from each other in the long term. CONCLUSIONS: CS after CDT for the treatment of ALLI is uncommon. Renal insufficiency is associated with an increased risk of CS. Fasciotomy prolongs the hospitalization. Patients with CS are exposed to an increased risk of major amputation.

Diffusion Monte Carlo simulations of gas phase and adsorbed D2-(H2)n clusters.

We have computed ground state energies and analyzed radial distributions for several gas phase and adsorbed D2(H2)n and HD(H2)n clusters. An external model potential designed to mimic ionic adsorption sites inside porous materials is used [M. Mella and E. Curotto, J. Phys. Chem. A 121, 5005 (2017)]. The isotopic substitution lowers the ground state energies by the expected amount based on the mass differences when these are compared with the energies of the pure clusters in the gas phase. A similar impact is found for adsorbed aggregates. The dissociation energy of D2 from the adsorbed clusters is always much higher than that of H2 from both pure and doped aggregates. Radial distributions of D2 and H2 are compared for both the gas phase and adsorbed species. For the gas phase clusters, two types of hydrogen-hydrogen interactions are considered: one based on the assumption that rotations and translations are adiabatically decoupled and the other based on nonisotropic four-dimensional potential. In the gas phase clusters of sufficiently large size, we find the heavier isotopomer more likely to be near the center of mass. However, there is a considerable overlap among the radial distributions of the two species. For the adsorbed clusters, we invariably find the heavy isotope located closer to the attractive interaction source than H2, and at the periphery of the aggregate, H2 molecules being substantially excluded from the interaction with the source. This finding rationalizes the dissociation energy results. For D2-(H2)n clusters with n≥12, such preference leads to the desorption of D2 from the aggregate, a phenomenon driven by the minimization of the total energy that can be obtained by reducing the confinement of (H2)12. The same happens for (H2)13, indicating that such an effect may be quite general and impact on the absorption of quantum species inside porous materials.

Are the intertidal fish highly resistant to UV-B radiation? A study based on oxidative stress in Girella laevifrons (Kyphosidae).

Sea chub, Girella laevifrons, is a coastal fish that inhabits high intertidal rockpools along the coast of Chile. The intertidal pools where the juveniles live, are an extreme environment with high levels of ultraviolet (UV) radiation, becoming harmful to the organisms, due to oxidative stress generated by reactive oxygen species. For this reason organisms develop adaptations that allow them to survive in this complex environment. The search of biomonitor species, sensitive to UV radiation is very important in aquatic ecosystems, mainly in the southern hemisphere where depletion of the ozone layer and the consequent increase of UV radiation, have become an environmental problem. The aim of this study was to evaluate the effect of ultraviolet radiation in G. laevifrons and its possible use as UV-B radiation biomonitor specie in intertidal systems, which are very important for the Chilean fisheries. The effect of UV radiation exposure on juvenile G. laevifrons was measured through oxidative stress parameters. Catalase's activity increased with the time of exposure, unlike superoxide dismutase's activity which peaked at 2h, decreasing towards the 5th hour of irradiation. The superoxide dismutase activity in muscle tissue did not show significant differences. The lipid peroxidation and DNA damage increased in relation to exposition times. Tissue muscle's DNA damage was shown only at 5h of exposure. Significant differences between the two organs in the antioxidant capacity were observed, the liver of G. laevifrons exhibited the higher antioxidant capacity. It can be concluded that this specie exhibits effective protection mechanisms against UV radiation exposure and it is not appropriate specie as a biomonitor in intertidal systems.

[Antimicrobial susceptibility, capsular serotypes and clonal relationship of invasive streptococcus pneumoniae isolates in adult population of the Bio-Bio region, Chile. 2005-2006]. / Susceptibilidad antimicrobiana, serotipos capsulares y relación clonal entre cepas invasoras de streptococcus pneumoniae aisladas de pacientes adultos de la Región del Bío-Bío, Chile. Periodo 2005-2006.

Streptococcus pneumoniae infections constitute a public health problem. In our country there is scarce information regarding isolates from bacteraemic episodes in adult population. The antibiotic susceptibility, serotypes and clonal relationship of 56 isolates of S. pneumoniae from adult patients with bacteraemic infections in Concepcion-Talcahuano, Bio-Bio Region, Chile, were studied. Resistance to tetracycline (21.4%), trimethoprim/ sulfamethoxazole (18%), erythromycin (18%), chloramphenicol (7%) and 1 penicillin resistant isolate from a meningeal focus (2%) was found. Also, all the isolates were susceptible to cefotaxime, levofloxacin, moxifloxacin and vancomycin. A wide variety of capsular serotypes was demonstrated, with predominance of serotypes 1, 5, 23F, 7F and 3. The macrorestriction analysis by pulse field electrophoresis revealed 31 electrophoretic patterns and 12 clonal groups, discarding a predominant clone. According to the results, at least, 80% of the S. pneumoniae serotypes isolated from bacteraemic adult patients are included in the available commercial vaccine.

Continuous improvement of safety in the Intensive Care and Surgical environment according to UNE 179003:2013 standard: 8 years experience. / Mejora continua de la seguridad en el ámbito de un Servicio de Anestesiología y Cuidados Intensivos a través de la certificación según la norma de UNE 179003:2013: 8 años de experiencia.

INTRODUCTION: The UNE 179003:2013 standard requires compliance with protocols to reduce the risks of patients from adverse events. METHODS: A description is presented of the procedure used in the Hospital Povisa to achieve UNE 179003:2010 certification for the intensive care unit, surgical division, and post-anaesthesia recovery unit (PARU). This was based on a risk management system, focusing on pro-active analysis using failure modes and effects analysis (FMEA) with the description of causes, consequences, risk weighting, and specific risk-minimising measures. A description is also presented of the analysis of reported adverse events (reactive analysis) in the Safety in Anesthesia and Resuscitation (SENSAR) notification system and the measures implemented over an eight-year period. RESULTS: The UNE 179003:2010 certification was obtained in July 2012, and the re-certification was achieved in July 2015. A total of 66 potential risks were established, which were weighted using a risk probability index (RPI), and measures were implemented that reduced this RPI by half. It also reflects the analysis of 1114 events declared in the SENSAR system over the past eight years, allowing for the introduction of 2681 measures, of which 98.4% are fully implemented. CONCLUSION: The application of the risk management methodology allowed (a) to improve safety in the area of action by reducing the risk to which the patients are subject, and (b) to gain certification in the UNE 179003 standard.

Enhancement of viability of muscle precursor cells on 3D scaffold in a perfusion bioreactor.

The aim of this study was to develop a methodology for the in vitro expansion of skeletal-muscle precursor cells (SMPC) in a three-dimensional (3D) environment in order to fabricate a cellularized artificial graft characterized by high density of viable cells and uniform cell distribution over the entire 3D domain. Cell seeding and culture within 3D porous scaffolds by conventional static techniques can lead to a uniform cell distribution only on the scaffold surface, whereas dynamic culture systems have the potential of allowing a uniform growth of SMPCs within the entire scaffold structure. In this work, we designed and developed a perfusion bioreactor able to ensure long-term culture conditions and uniform flow of medium through 3D collagen sponges. A mathematical model to assist the design of the experimental setup and of the operative conditions was developed. The effects of dynamic vs static culture in terms of cell viability and spatial distribution within 3D collagen scaffolds were evaluated at 1, 4 and 7 days and for different flow rates of 1, 2, 3.5 and 4.5 ml/min using C2C12 muscle cell line and SMPCs derived from satellite cells. C2C12 cells, after 7 days of culture in our bioreactor, perfused applying a 3.5 ml/min flow rate, showed a higher viability resulting in a three-fold increase when compared with the same parameter evaluated for cultures kept under static conditions. In addition, dynamic culture resulted in a more uniform 3D cell distribution. The 3.5 ml/min flow rate in the bioreactor was also applied to satellite cell-derived SMPCs cultured on 3D collagen scaffolds. The dynamic culture conditions improved cell viability leading to higher cell density and uniform distribution throughout the entire 3D collagen sponge for both C2C12 and satellite cells.

[Impact of infectious diseases specialist evaluation on the rational use of antibiotics in patients with Streptococcus pneumoniae bacteremia]. / Impacto de la evaluación infectológica en el uso racional de antimicrobianos en pacientes con bacteriemia por Streptococcus pneumoniae.

The increasing reporting of Streptococcus pneumoniae resistance to penicillin has lead to the recommendation of third generation cephalospirins for the treatment of serious pneumococcal infections. As a consequence, clinicians usually do not prescribe first line antibiotics despiste the availability of susceptibility studies. Whit the aim to evaluate the impact of the infectious diseases specialist evaluation in the apropriate use oh the susceptibility studies, two series were compared: a historic control one (1998-2002, n = 50) and a prospectuve group that had the advisement of one infectious diseases specialist (2003-2006, n = 60). In both series, pneumonia stood out as the source of the bacteremia, and -alcoholism/hepatic insufficiency as associated factor. In the first series, 48 isolates resulted susceptible to penicillin by agar diffusion, and 1 out of 36 patients with pneumonia had a change in the antibiotic therapy to penicillin. In the prospective series, we found 56 susceptible isolates, and the remaining four were classified as intermediate susceptibility according to the MIC value. Antibiotics were changed in 36 out of 50 patients with bacteremic pneumococcal pneumonia (p < 0.05). The infectious diseases specialist evaluation had a positive impact on the use of the microbiological information for therapeutics purposes.

[Extended spectrum beta lactamases (ESBL) production in Acinetobacter baumannii strains isolated from Chilean hospitals belonging to VIII Region]. / Producción de beta-lactamasas de espectro extendido (BLEE) en cepas de Acinetobacter baumannii aisladas en hospitales de la VIIIa Región, Chile.

The resistance of Acinetobacter baumannii to ss-lactam antibiotics is mainly due to the synthesis of ss-lactamases. From a clinical point of view, this bacteria and others, grouped under the acronym SPACE (S: Serratia, P: Pseudomonas, A: Acinetobacter, C: Citrobacter, E: Enterobacter) are essentially Amp-C ss-lactamases producers. There is no local information about ESBL presence in Acinetobacter. We studied ESBL production using the Ho and col. technique modified by adding cloxacillin as chromosomal ss-lactamases inhibitor. From 69 isolates, with resistance to at least one third generation cephalosporin, only 7 showed positive synergy test. Four of these amplified for TEM family gene, and one of these amplified also for the OXA family. Our study found a low ESBL production percentage, which agrees with the premise of Amp-C as the main mechanism of resistance to ss-lactam antibiotics in A. baumannii. However, the ESBL description in these bacteria emphasizes the capacity of expressing multiple resistance mechanisms.

"Leaching or not leaching": an alternative approach to antimicrobial materials via copolymers containing crown ethers as active groups.

In this work, new copolymers containing either MMA and 18C6 crown-ether pendants, or PEG, MMA and 18C6 crown-ether pendants were synthesized to test the idea that sequestering structural alkali-earth ions from the bacterial outer membrane (OM) may lead to bacterial death. The copolymers were obtained either via uncontrolled radical polymerization or ATRP; the latter approached allowed us to produce not only linear copolymers but also branched Y-like structures. After checking for the capability of complexing magnesium and calcium ions, the antimicrobial activity of all copolymers was tested placing their casted plaques in contact with pure water E. coli suspensions. All plaques adsorbed alkali-earth ions and killed bacteria, albeit with different antimicrobial efficiencies. Differences in the latter characteristic were attributed to different plaque roughness. The role of the 18C6 crown-ether pendants was elucidated by pre-saturating plaques with Mg/Ca ions, the marked reduction in antimicrobial efficiency indicating that losing the latter from OM due to surface complexation does play an important role in killing bacteria at short (<5 h) contact times. At longer times, the mode of action is instead related to the poly-cationic nature acquired by the plaques due to ion sequestering.

Human anaplasmosis: the first Spanish case confirmed by PCR.

We report a case of human anaplasmosis (HA) fulfilling the confirmation criteria: epidemiologic data and clinical picture compatible with HA; presence of a morulae within polymorphonuclear leukocyte; and positive PCR assay for Anaplasma phagocytophilum: This case report shows the presence of HA in Spain.

Novel adrenoceptor antagonists with a tricyclic pyrrolodipyridazine skeleton.

A still unknown tricyclic heterocyclic system (5) was synthesized from 6-hydroxy-2-methylpyridazin-3-one and its structure identified as 2,8-dichloro-6-methylpyrrolo[1,2-b:3,4-d']dipyridazin-5(6H)- one by spectroscopic investigations. Selective condensation of 5 with 2-[4-(2-substituted-phenyl)piperazin-1-yl]ethylamine gave the 2-arylpiperazinylethylamino-8-chloro derivatives 6a-c, which were investigated in binding studies toward the three alpha1-adrenergic and 5-HT1A-serotonergic receptor subtypes. They displayed high potency on all the assays and some selectivity for alpha1a and alpha1d subtypes.

Photoinduced C-F Bond Cleavage in Some Fluorinated 7-Amino-4-quinolone-3-carboxylic Acids.

The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water. All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution. 6-Fluoro derivatives such as norfloxacin (Phi(dec) = 0.06) and enoxacin (Phi(dec) = 0.13) give the corresponding phenols. Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Phi(dec) = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain). With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (Phi = 0.55) and selective for position 8. Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N-ethyl group rather than solvent addition (a carbene-like chemistry). With all of the above fluoroquinolones an intensive triplet-triplet absorption is detected and is quenched by sulfite (k(q) = (1-5) x 10(8) M(-)(1) s(-)(1)). Under this condition, reductive defluorination via the radical anion takes place. The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.

Photochemical alkylation of ketene dithioacetal S,S-dioxides. An example of captodative olefin functionalization

Radical alkylation of some ketene dithioacetal S,S-dioxides failed through the tin hydride promoted chain process but was successfully performed through stoichiometric photochemical initiation, either by electron transfer or hydrogen abstraction. In the first case, alkyl radicals were produced from tetralkylstannanes (t-Bu-, i-Pr-, n-Bu-SnR(3)) via radical cation fragmentation, while in the second case these were produced from alkanes (cyclohexane, adamantane) by benzophenone triplet. When bulky radicals (t-Bu, adamantyl) were involved, the addition occurred with complete diastereoselectivity.

Topical administration of tetrasodium-meso-tetraphenyl-porphinesulfonate (TPPS): correlation between drug penetration and depth of necrosis in skin of nude mice following red light irradiation.

The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. We tested the photosensitizing properties of a 2% solution of TPPS (tetrasodium-tetraphenylporphinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after application. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 nm, 4 h after TPPS application, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this metodology need further investigation.

Improved diffusion Monte Carlo for bosonic systems using time-step extrapolation "on the fly".

A diffusion Monte Carlo algorithm employing "on the fly" extrapolation with respect to the time step is implemented and demonstrated simulating realistic systems. Significant advantages are obtained when using on the fly extrapolation, leading to reduced systematic and statistical errors. The sound theoretical basis of extrapolation on the fly is discussed and compared to justifications for the a posteriori extrapolation.

Application of valence-bond techniques to the study of weakly bound complexes. The potential energy surface of the Ne-CH(4) system.

We present a comprehensive survey of the Molecular Orbital-Valence Bond (MO-VB) method, a theoretical scheme developed within the framework of the Valence Bond theory to deal with weakly bound intermolecular complexes. According to the MO-VB, the wavefunction of the system is expressed as a truncated non-orthogonal Configuration Interaction expansion, which is size extensive and a priori free of basis set superposition error. We report on the recent developments of the method, which extend the range of application of the MO-VB to intermolecular complexes with a quite large number of correlated electrons, showing that VB-based methods are nowadays a valid alternative to Molecular Orbital approaches also in this field. The MO-VB has been applied to study extensively the Ne-CH(4) complex, and compared with the more standard MP4 and CCSD(T) results. We determined two analytical Potential Energy Surfaces (PES) for this system, computed at MO-VB and MP4 level, which represent the first ones coming entirely from ab initio computations. The features of our potentials are discussed, and compared to the single analytical potential which includes the anisotropy available in the literature, determined about twenty years ago by Udo Buck and co-workers using a semiempirical approach [U. Buck, A. Kolhase, D. Secrest, T. Phillips, G. Scoles and F. Grein, Mol. Phys., 1985, 55, 1233]. The differences among the three PES are quite relevant, and are due to play a relevant role in the theoretical simulations of the dynamical properties of the Ne-CH(4) system.

[Mutations in gyrA and gyrB genes among strains of Gram-negative bacilli isolated from Chilean hospitals and their relation with resistance to fluoroquinolones]. / Mutaciones en genes gyrA y gyrB en cepas de bacilos Gram negativos aisladas en hospitales chilenos y su relación con la resistencia a fluoroquinolonas.

BACKGROUND: A progressive frequency of resistance to fluoroquinolones is observed among Gram-negative bacilli. AIM: To investigate the mechanism of resistance to fluoroquinolones mediated by mutations affecting gyrA and gyrB genes in strains of Gram negative bacüli isolated from CMean hospitals. MATERIAL AND METHOD: Minimal inhibitory concentration of fluoroquinolones was determined in 91 randomly selected nalidixic acid-resistant strains of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, isolated from hospitals of 12 Chilean cities. Quinolone resistance determining region (QRDR) was amplified by PCR and mutations were determined by restriction fragment length polymorphism (RFLP) and DNA sequencing. RESULTS: Strains with mutation in codon 83 of gyrA showed decreased susceptibility to ciprofloxacin with MICs ranging from 0.25 to 1024 fig/ml. The sequencing of PCR products for gyrA indicated amino acid changes in the QRDR region. One strain ofE. coli presented a double mutation, in codon 83 Ser to Leu as well as in codon 87 Asp to Asn. In strains ofK. pneumoniae, however, the change of codon 83 was Ser to Tyr, in A. baumannii was Ser to Leu and in P. aeruginosa was Thr to He. No strains with mutations affecting gyrB were found. CONCLUSIONS: Mutations in codon 83 of gyrA is a frequent genetic event involved in the mechanism leading to decreased susceptibility to fluoroquinolone in strains of Gram-negative bacilli.