Supramolecular nanocapsules as two-fold stabilizers of outer-cavity sub-nanometric Ru NPs and inner-cavity ultra-small Ru clusters.

The synthesis of metallic nanoparticles (MNP) with high surface area and controlled shape is of paramount importance to increase their catalytic performance. The detailed growing process of NP is mostly unknown and understanding the specific steps would pave the way for a rational synthesis of the desired MNP. Here we take advantage of the stabilization properties exerted by the tetragonal prismatic supramolecular nanocapsule 8·(BArF)8 to develop a synthetic methodology for sub-nanometric RuNP (0.6-0.7 nm). The catalytic properties of these sub-nanometric nanoparticles were tested on the hydrogenation of styrene, obtaining excellent selectivity for the hydrogenation of the alkene moiety. In addition, the encapsulation of [Ru5] clusters inside the nanocapsule is strikingly observed in most of the experimental conditions, as ascertained by HR-MS. Moreover, a thorough DFT study enlightens the nature of the [Ru5] clusters as tb-Ru5H2(η6-PhH)2(η6-pyz)3 (2) trapped by two arene moieties of the clip, or as tb-Ru5H2(η1-pyz)6(η6-pyz)3 (3) trapped between the two Zn-porphyrin units of the nanocapsule. Both options fulfill the Wade-Mingos counting rules, i.e. 72 CVEs for the closotb. The trapped [Ru5] metallic clusters are proposed to be the first-grown seeds of subsequent formation of the subnanometric RuNP. Moreover, the double role of the nanocapsule in stabilising ∼0.7 nm NPs and also in hosting ultra-small Ru clusters, is unprecedented and may pave the way towards the synthesis of ultra-small metallic clusters for catalytic purposes.

Moderate to Intense Physical Activity Is Associated With Improved Clinical, CD4/CD8 Ratio, and Immune Activation Status in HIV-Infected Patients on ART.

BACKGROUND: Physical activity has anti-inflammatory effects and reduces morbidity and mortality in the general population, but its role in the clinical, CD4/CD8 ratio, and immune activation status of HIV-infected patients has been poorly studied. METHODS: A cross-sectional study was carried out in a cohort of 155 HIV-infected patients on stable antiretroviral therapy (ART) to compare clinical, biochemical, CD4/CD8 ratio, and immune activation status according to their physical activity in the last 2 years (sedentary/low vs moderate/intense) assessed by the iPAQ. A binary logistic regression and mixed analysis of variance were performed to evaluate the impact of levels of physical activity on CD4/CD8 ratio. RESULTS: In our series, 77 (49.7%) out of 155 patients were sedentary, and 78 (50.3%) practiced moderate/intense physical activity. Moderate/intense physical activity was associated with better metabolic control (lower body mass index, P = .024; glucose, P = .024; and triglyceride, P = .002) and CDC HIV stage (P = .046), lower CD8+ (P =  .018), CD4+CD8+ (P = .026), CD4+CD86+ (P = .045), CD4+HLA-DR+ (P = .011), CD8+HLA-DR+ (P = .048) T lymphocytes and CD16+HLA-DR+ natural killer cells (P = .026), and higher CD3+CD4+ T lymphocytes (P = .016) and CD4/CD8 ratio (P = .001). Sedentary lifestyle (odds ratio [OR], 2.12; P = .042), CD4 nadir (OR, 1.005; P < .001), and CD8+CD38+ T cells (OR, 1.27; P = .006) were independently associated with low CD4/CD8 ratio (<0.8). Earlier and more intense CD4/CD8 ratio recovery was observed in patients with higher physical activity in the 2-year follow-up with a significant interaction between these variables: F(2, 124) = 3.31; P = .049; partial η2 = 0.042. CONCLUSIONS: Moderate to high physical activity is associated with beneficial health effects, improvement in metabolic profile, and reduction of chronic inflammation in patients with HIV. Although more studies and clinical trials are needed to confirm these findings, a healthy lifestyle including at least moderate physical activity should be recommended to HIV patients on stable ART.

Magnetically Induced Catalytic Reduction of Biomass-Derived Oxygenated Compounds in Water.

The development of energetically efficient processes for the aqueous reduction of biomass-derived compounds into chemicals is key for the optimal transformation of biomass. Herein we report an early example of the reduction of biomass-derived oxygenated compounds in water by magnetically induced catalysis. Non-coated and carbon-coated core-shell FeCo@Ni magnetic nanoparticles were used as the heating agent and the catalyst simultaneously. In this way it was possible to control the product distribution by adjusting the field amplitude applied during the magnetic catalysis, opening a precedent for this type of catalysis. Finally, the encapsulation of the magnetic nanoparticles in carbon (FeCo@Ni@C) strongly improved the stability of the magnetic catalyst in solution, making its reuse possible up to at least eight times in dioxane and four times in water.

Bimetallic Nanoparticles Associating Noble Metals and First-Row Transition Metals in Catalysis.

Bimetallic nanoparticles (NPs) are complex systems with properties that far exceed those of the individual constituents. In particular, association of a noble metal and a first-row transition metal are attracting increasing interest for applications in catalysis, electrocatalysis, and magnetism, among others. Such objects display a rich structural chemistry thanks to their ability to form intermetallic phases, random alloys, or core-shell species. However, under reaction conditions, the surface of these nanostructures may be modified due to migration, segregation, or isolation of single atoms, leading to the formation of original structures with enhanced catalytic activity. In this respect, Zakhtser et al. report in this issue of ACS Nano the synthesis and study of the chemical evolution of the surface of a series of PtZn nanostructured alloys. In this Perspective, we report some selected examples of bimetallic nanocatalysts and their increased activity compared to that of the corresponding pure noble metal, with a special focus on Pt-based systems. We also discuss the mobility of the species present on the catalyst surface and the electronic influence of one metal to the other.

Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals.

Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late-stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air-stable iridium precatalyst [Ir(COD)(OMe)]2 is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa-/thia-zoles, thiophene, but also electron-rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.

Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. METHODS: This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p <0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25-10.14; p < 0.001) in multivariate analysis. MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612-0.850, p <0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p <0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79-10.1, p < 0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537-0.764) and AUROC of 0.700 (CI 95% 0.594-0.800), respectively (p < 0.05 for both). CONCLUSIONS: MR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low.

Electronic Structures of Mono-Oxidized Copper and Nickel Phosphasalen Complexes.

Non-innocent ligands render the determination of the electronic structure in metal complexes difficult. As such, a combination of experimental techniques and quantum chemistry are required to correctly elucidate them. This paper deals with the one-electron oxidation of copper(II) and nickel(II) complexes featuring a phosphasalen ligand (Psalen), which differs from salen analogues by the presence of iminophosphorane groups (P=N) instead of imines. Various experimental techniques (X-ray diffraction, cyclic voltammetry, NMR, EPR, and UV/Vis spectroscopies, and magnetic measurements) as well as quantum chemical calculations were used to define the electronic structure of the oxidized complexes. These can be modified by a small change in the ligand structure, that is, the replacement of a tert-butyl group by a methoxy on the phenoxide ring. The different techniques have allowed quantifying the amount of spin density located on the metal center and on the Psalen ligands. All complexes were found to possess a multi-configurational ground state, in which the ratio of the +II versus +III oxidation state of the metal center, and therefore the phenolate versus phenoxyl radical ligand character, varies upon the substituents. The tert-butyl group favors a strong localization on the metal center whereas with the methoxy group the metallic configurations decrease and the ligand configurations increase. The importance of the geometrical considerations compared with the electronic substituent effect is highlighted by the differences observed between the solid-state (EPR, magnetic measurements) and solution characterizations (EPR and NMR data).

El fragmento N-terminal del propéptido natriurético cerebral es el mejor predictor de mortalidad intrahospitalaria en pacientes con sepsis y bajo riesgo de lesión orgánica / The N-terminal pro brain natriuretic peptide is the best predictor of mortality during hospitalization in patients with low risk of sepsis-related organ failure

Introducción: El objetivo de este estudio fue investigar el valor del fragmento N-terminal del propéptido natriurético cerebral (NT-proBNP), proteína C reactiva (PCR) y procalcitonina (PCT) para predecir la mortalidad en pacientes sépticos durante la hospitalización con un riesgo de mortalidad<10% evaluado por el Sepsis-related Organ Failure Assessment (SOFA). Material y métodos: Estudio observacional prospectivo realizado en pacientes hospitalizados con sepsis y riesgo SOFA<10%. Los biomarcadores se obtuvieron en las primeras 72h después del ingreso en el hospital. Todos fueron monitorizados durante la hospitalización o hasta la muerte. Se utilizaron las curvas ROC para determinar el área bajo la curva (ABC) e identificar las mejores concentraciones de corte para predecir la mortalidad. Resultados: Se analizaron un total de 174 pacientes. Diecisiete (9,8%) pacientes murieron durante la hospitalización. El ABC de NT-proBNP fue 0,793 (IC 95% 0,686-0,9; p<0,0005) en comparación con el ABC de la PCR (0,728; IC 95% 0,617-0,839; p=0,004) y el ABC del PCT (0,684; IC 95% 0,557-0,811; p=0,019). Los factores asociados a la mortalidad hospitalaria fueron: tener un NT-proBNP>1.330pg/ml (OR=23,23; IC 95% 2,92-182,25; p=0,003) y tener factores predisponentes para presentar sepsis (OR=3,05; IC 95% 1,3-9,3; p=0,044). Conclusiones: En pacientes con bajo riesgo de mortalidad según la puntuación SOFA, los niveles de NT-proBNP obtenidos en las primeras 72h después del ingreso son un poderoso predictor de mortalidad. Su implementación en la práctica clínica podría mejorar la capacidad predictiva de la puntuación de gravedad clínica en estos pacientes (AU)

Introduction: The purpose of this study was to investigate the value of N-terminal pro brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and procalcitonin (PCT) in predicting mortality in septic patients during hospitalization with mortality risk<10% evaluated by Sepsis-related Organ Failure Assessment (SOFA). Material and methods: Prospective, observational study performed in sepsis patients with SOFA risk<10%. We obtained levels of biomarkers in the first 72h after admission in hospital. All patients were monitored during hospitalization or until death. We used ROC curves to determine area under curve (AUC) and identify the best cutoff concentrations to predict mortality. Results: A total of 174 patients were analyzed. Seventeen (9.8%) patients died during hospitalization. The AUC of NT-proBNP was 0.793 (95% CI 0.686-0.9; P<.0005) compared to AUC of CRP (0.728; 95% CI 0.617-0.839; P=.004) and AUC of PCT (0.684; 95% CI 0.557-0.811; P=.019). Factors independently associated with in-hospital mortality were NT-proBNP>1,330pg/ml (OR=23.23; 95% CI 2.92-182.25; P=.003) and to have predisposing factors (OR=3.05; 95% CI 1.3-9.3; P=.044). Conclusions: In patients with low mortality risk according to SOFA score, NT-proBNP obtained in the first 72h after admission prove to be a powerful predictor of mortality. Their implementations in clinical practice would improve the predictive ability of clinical severity scores (AU)

[Nomogram to predict a poor outcome in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA)]. / Nomograma para predecir mal pronóstico en pacientes procedentes de urgencias con sepsis y bajo riesgo de daño orgánico evaluado mediante SOFA.

OBJECTIVES: To develop a nomograph to predict a poor outcome (death during hospitalization or a hospital stay longer than 15 days) in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA). MATERIAL AND METHODS: Prospective, observational study carried out in a single universitary hospital. All patients admitted from the emergency department with sepsis and SOFA scores of 6 or lower were enrolled. We used bivariate logistic regression analysis to develop a predictive nomogram. RESULTS: A total of 174 patients were included. Seventeen patients (9.8%) died during hospitalization and the average hospital stay was greater than 15 days in 29 (16.7%) patient. The outcome was poor in a total of 42 patients (24.1%);. Independent variables that were significantly associated with a poor outcome were SOFA score (odds ratio [OR], 1.3; 95% CI, 1.06-1.71; P<.05), C-reactive protein (CRP) concentration (OR, 1.04; 95% CI, 1.0-1.09; P<.05), N-terminal fragment of brain natriuretic peptide (NT-proBNP) concentration over 1330 ng/mL (OR, 2.64; 95% CI, 1.17-6.22; P<.05), and septic shock (OR, 8.3; 95% CI, 1.16-166.5; P<.05). For a SOFA score of 2 or more the crude OR was 4.44 (95%, CI, 1.91-10.34) and the OR adjusted for other variables was 3.08 (95% CI, 1.24-7.69). CONCLUSION: A high percentage of patients predicted to be at low risk of organ failure had poor outcomes, associated with SOFA score, the presence of septic shock, CRP concentration, and elevated NT-proBNP concentration. The SOFA score by itself is an inadequate prognostic tool in patients at low risk of organ damage. Other clinical and analytical variables are required to complement the SOFA score.

OBJETIVO: Elaborar un nomograma que permita predecir el mal pronóstico (mortalidad durante el ingreso o estancia media > 15 días) en pacientes procedentes de urgencias con sepsis y baja probabilidad de daño orgánico evaluado por SOFA (Sepsis-related Organ Failure Assessment). METODO: Estudio observacional prospectivo realizado en un único hospital. Se incluyeron de forma consecutiva pacientes del servicio de urgencias con sepsis y SOFA igual o inferior a 6 puntos. Se realizó un análisis de regresión logística binaria y se elaboró un nomograma predictivo. RESULTADOS: Se incluyeron 174 pacientes. Diecisiete (9,8%) pacientes fallecieron durante la hospitalización y 29 (16,7%) tuvieron una estancia media prolongada. En total, 42 (24,1%) pacientes tuvieron mal pronóstico. Las variables independientes de mal pronóstico fueron: la puntuación SOFA (OR 1,3; IC 95% 1,06-1,71; p < 0,05), las concentraciones de proteína C reactiva (PCR) (OR 1,04; IC 95% 1-1,09; p < 0,05), NT-proBNP > 1.330 ng/ml (OR 2,64; IC 95% 1,17-6,22; p < 0,05) y la presencia de shock séptico (OR 8,3; IC 95% 1,16-166,5; p < 0,05). Si tenemos en cuenta el índice SOFA >= 2, la OR cruda fue 4,44 (IC 95% 1,91-10,34) y ajustada por el resto de variables fue de 3,08 (IC 95%, 1,24-7,69). CONCLUSIONES: Una elevada proporción de pacientes con baja probabilidad de tener daño orgánico tuvieron mal pronóstico en relación con la puntuación en la escala SOFA, la presencia de shock séptico, concentraciones de PCR y NTproBNP. La utilización de la escala pronóstica SOFA en pacientes con bajo riesgo es insuficiente para predecir el pronóstico en estos pacientes y se hace necesario complementarla con otras variables clínicas y analíticas.

Patient experience in the pediatric emergency department: do parents and children feel the same?

The objectives are to describe the experience of children and parents in a pediatric emergency service (PED) and to determine whether there are differences of opinion between the two groups. This was a descriptive study. A questionnaire was designed based on the Picker questionnaire on the patient experience. From July through December 2015, a survey was made of the children aged 8-18 treated in the PED, as well as of their parents. The proportion of dissatisfaction was determined. A total of 514 questionnaires (257 children, 257 parents) were completed. The most poorly rated aspects according to the children and parents were the entertainment activities (43.2%), the waiting time (23.7%), and the treatment for pain (10.5%). Differences were detected in the experiences of the children and the parents regarding the overlong waiting time (28.0% children vs 19.5% parents; p = 0.023), inadequate explanations (7.0 vs 1.6%, p = 0.002), inadequate treatment for pain (14.4 vs 6.6%; p = 0.004), and insufficient privacy (11.7 vs 2.7%; p < 0.001). CONCLUSION: The entertainment activities during the wait and the waiting time are the two elements viewed most negatively by the children and the parents. The children tend to evaluate certain aspects of their experience as patients more negatively, which needs to be borne in mind in order to improve the attention provided. What is Known: • Studying the experience of patients is a key point in patient-centered medicine. • The experience of the pediatric patient has been little studied to date. The experience of the children is often inferred from that of their parents. Nevertheless, the experience of the children as patients might be different. What is New: • Overall, the experience of children and parents in the pediatric emergency department in the study is positive. Some aspects of the experience in emergency are poorly rated by the children, such as the waiting time, the information provided, treatment for pain, and privacy during the visit. • The experience of the children (and not merely that of their parents) needs to be studied in order to improve those areas that are rated poorly do as to enrich the experience in the emergency department.

The N-terminal pro brain natriuretic peptide is the best predictor of mortality during hospitalization in patients with low risk of sepsis-related organ failure. / El fragmento N-terminal del propéptido natriurético cerebral es el mejor predictor de mortalidad intrahospitalaria en pacientes con sepsis y bajo riesgo de lesión orgánica.

INTRODUCTION: The purpose of this study was to investigate the value of N-terminal pro brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and procalcitonin (PCT) in predicting mortality in septic patients during hospitalization with mortality risk<10% evaluated by Sepsis-related Organ Failure Assessment (SOFA). MATERIAL AND METHODS: Prospective, observational study performed in sepsis patients with SOFA risk<10%. We obtained levels of biomarkers in the first 72h after admission in hospital. All patients were monitored during hospitalization or until death. We used ROC curves to determine area under curve (AUC) and identify the best cutoff concentrations to predict mortality. RESULTS: A total of 174 patients were analyzed. Seventeen (9.8%) patients died during hospitalization. The AUC of NT-proBNP was 0.793 (95% CI 0.686-0.9; P<.0005) compared to AUC of CRP (0.728; 95% CI 0.617-0.839; P=.004) and AUC of PCT (0.684; 95% CI 0.557-0.811; P=.019). Factors independently associated with in-hospital mortality were NT-proBNP>1,330pg/ml (OR=23.23; 95% CI 2.92-182.25; P=.003) and to have predisposing factors (OR=3.05; 95% CI 1.3-9.3; P=.044) CONCLUSIONS: In patients with low mortality risk according to SOFA score, NT-proBNP obtained in the first 72h after admission prove to be a powerful predictor of mortality. Their implementations in clinical practice would improve the predictive ability of clinical severity scores.

Nomograma para predecir mal pronóstico en pacientes procedentes de urgencias con sepsis y bajo riesgo de daño orgánico evaluado mediante SOFA / Nomogram to predict a poor outcome in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA)

Objetivo: Elaborar un nomograma que permita predecir el mal pronóstico (mortalidad durante el ingreso o estancia media > 15 días) en pacientes procedentes de urgencias con sepsis y baja probabilidad de daño orgánico evaluado por SOFA (Sepsis-related Organ Failure Assessment). Método: Estudio observacional prospectivo realizado en un único hospital. Se incluyeron de forma consecutiva pacientes del servicio de urgencias con sepsis y SOFA igual o inferior a 6 puntos. Se realizó un análisis de regresión logística binaria y se elaboró un nomograma predictivo. Resultados: Se incluyeron 174 pacientes. Diecisiete (9,8%) pacientes fallecieron durante la hospitalización y 29 (16,7%) tuvieron una estancia media prolongada. En total, 42 (24,1%) pacientes tuvieron mal pronóstico. Las variables independientes de mal pronóstico fueron: la puntuación SOFA (OR 1,3; IC 95% 1,06-1,71; p < 0,05), las concentraciones de proteína C reactiva (PCR) (OR 1,04; IC 95% 1-1,09; p < 0,05), NT-proBNP > 1.330 ng/ml (OR 2,64; IC 95% 1,17-6,22; p < 0,05) y la presencia de shock séptico (OR 8,3; IC 95% 1,16-166,5; p < 0,05). Si tenemos en cuenta el índice SOFA _ 2, la OR cruda fue 4,44 (IC 95% 1,91-10,34) y ajustada por el resto de variables fue de 3,08 (IC 95%, 1,24-7,69). Conclusiones: Una elevada proporción de pacientes con baja probabilidad de tener daño orgánico tuvieron mal pronóstico en relación con la puntuación en la escala SOFA, la presencia de shock séptico, concentraciones de PCR y NTproBNP. La utilización de la escala pronóstica SOFA en pacientes con bajo riesgo es insuficiente para predecir el pronóstico en estos pacientes y se hace necesario complementarla con otras variables clínicas y analíticas (AU)

Objective: To develop a nomograph to predict a poor outcome (death during hospitalization or a hospital stay longer than 15 days) in emergency patients with sepsis and at low risk of organ damage according to Sepsis-related Organ Failure Assessment (SOFA). Methods: Prospective, observational study carried out in a single universitary hospital. All patients admitted from the emergency department with sepsis and SOFA scores of 6 or lower were enrolled. We used bivariate logistic regression analysis to develop a predictive nomogram. Results: A total of 174 patients were included. Seventeen patients (9.8%) died during hospitalization and the average hospital stay was greater than 15 days in 29 (16.7%) patient. The outcome was poor in a total of 42 patients (24.1%);. Independent variables that were significantly associated with a poor outcome were SOFA score (odds ratio [OR], 1.3; 95% CI, 1.06-1.71; P<.05), C-reactive protein (CRP) concentration (OR, 1.04; 95% CI, 1.0-1.09; P<.05), N-terminal fragment of brain natriuretic peptide (NT-proBNP) concentration over 1330 ng/mL (OR, 2.64; 95% CI, 1.17-6.22; P<.05), and septic shock (OR, 8.3; 95% CI, 1.16-166.5; P<.05). For a SOFA score of 2 or more the crude OR was 4.44 (95%, CI, 1.91-10.34) and the OR adjusted for other variables was 3.08 (95% CI, 1.24-7.69). Conclusions: A high percentage of patients predicted to be at low risk of organ failure had poor outcomes, associated with SOFA score, the presence of septic shock, CRP concentration, and elevated NT-proBNP concentration. The SOFA score by itself is an inadequate prognostic tool in patients at low risk of organ damage. Other clinical and analytical variables are required to complement the SOFA score (AU)

Statins in HIV-Infected Patients: Potential Beneficial Effects and Clinical Use.

Patients living with HIV have an increased risk of cardiovascular disease that is considered to be the result of an interaction between traditional cardiovascular risk factors, particularly smoking and dyslipidemia, and persistent chronic inflammation and immune activation associated with HIV infection, along with side effects of antiretroviral therapy. In the general population, the administration of statins has been associated with a reduction in cardiovascular disease-associated mortality, and these drugs are among the most common class of medication prescribed in high-income countries. The beneficial effect of statins extends beyond reducing cholesterol levels as they have been shown to have anti- inflammatory, antithrombotic, antioxidant, immunomodulatory, and vasodilatory effects, and to improve endothelial function. Despite the widespread use of statins in the general population, cohort studies show that these drugs are underutilized in HIV-infected patients, probably due to safety concerns by clinicians and limited data evaluating clinical outcomes in patients on antiretroviral therapy. In this article we review and update the most important clinical studies of statins in HIV- infected patients, describe their side effects and interaction profiles, and discuss the anti-atherosclerotic and pleiotropic effects of these drugs. Finally, we propose recommendations for clinical use of statins in patients living with HIV.

The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment.

Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 ± 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 ± 0.16 mm vs. 0.63 ± 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019]. In conclusion, the inversion of CD4/CD8 ratio in treated HIV-infected patients is independently associated with cIMT progression, a marker of coronary heart disease. Therefore, it might be clinically useful as predictor of cardiovascular events.

Chemical Composition, Antioxidant and Antimicrobial Activity of Essential Oils from Organic Fennel, Parsley, and Lavender from Spain.

The aim of this work was to (i) determine the chemical composition of the essential oils of three spices widely cultivated in Spain from organic growth: Foeniculum vulgare, Petroselium crispum, and Lavandula officinalis; (ii) determine the total phenolic content; (iii) determine the antioxidant activity of the essentials oils by means of three different antioxidant tests and (iv) determine the effectiveness of these essentials oils on the inhibition of Listeria innocua CECT 910 and Pseudomonas fluorescens CECT 844. There is a great variability in the chemical composition of the essential oils. Parsley had the highest phenolic content. Overall, parsley presented the best antioxidant profile, given its highest % of inhibition of DPPH radical (64.28%) and FRAP (0.93 mmol/L Trolox), but had a pro-oxidative behavior by TBARS. Lavender essential oil showed the highest antibacterial activity against L. innocua (>13 mm of inhibition at 20-40 µL oil in the discs), followed by parsley with an inhibition zone of 10 mm (when more than 5 µL oil in the discs), and fennel 10 mm (when more than 40 µL oil in the discs). P. fluorescens was not inhibited by the tested essential oils.

Subacute cutaneous lupus erythematosus starting as linear lupus erythematosus.

BACKGROUND: Cutaneous lupus in childhood is usually associated with systemic lupus erythematosus (LE). Linear cutaneous LE (LCLE) is an unusual presentation mostly seen in children and young adults. METHODS: We report a rare case of cutaneous subacute LE with a segmentary pattern following the lines of Blaschko in an 18-month-old girl with a 2-month history of persistent, linear, asymptomatic, erythematous lesions along the right arm. The clinical diagnosis at presentation was lichen striatus. RESULTS: A biopsy showed an intense, band-like, inflammatory cell infiltrate with perivascular and periadnexal involvement associated with basal cell liquefactive degeneration. The lesions were treated with topical corticosteroids and healed without scarring. Two months later, new lesions manifested as multiple erythematous, edematous, polycyclic plaques. A new biopsy showed a periadnexal infiltrate, a large amount of mucin, and a thickened basement membrane. Direct immunofluorescence was negative. Our definitive diagnosis was subacute cutaneous LE starting as linear LE. The lesions responded slowly to oral corticosteroids. Six months later, only a mild livedoid skin pattern remained on the patient's legs. CONCLUSIONS: Linear cutaneous LE usually presents with erythematous, atrophic, hyperkeratotic, dyschromic circular lesions arranged in a linear pattern; the main differential diagnosis is lichen striatum. In general, LCLE can be considered as discoid lupus following Blaschko's lines, which correspond to the direction of growth in clones of cutaneous cells that arise during embryogenesis. The present patient represents the first pediatric case of subacute cutaneous LE following Blaschko's lines, with posterior progression to a generalized form of subacute LE.

Successive light-induced two electron transfers in a Ru-Fe supramolecular assembly: from Ru-Fe(ii)-OH2 to Ru-Fe(iv)-oxo.

In the present work we describe the synthesis and study of a RuII-FeII chromophore-catalyst assembly designed to perform the light-induced activation of an iron bound water molecule and subsequent photo-driven oxidation of a substrate. Using a series of spectroscopic techniques, we demonstrate that excitation of the chromophore unit with 450 nm light, in the presence of a sacrificial electron acceptor, triggers a cascade of electron transfers leading to the formation of a high valent iron(iv)-oxo center from an iron(ii)-bound water molecule. The activity of this catalytic center is illustrated by the oxidation of triphenyl phosphine.

The CD4:CD8 ratio is associated with IMT progression in HIV-infected patients on antiretroviral treatment.

INTRODUCTION: Inversion of the CD4:CD8 ratio (<1) has been identified as a hallmark of immunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and intima-media thickness (IMT) progression in treated HIV-infected patients as a marker of early atherosclerosis. MATERIALS AND METHODS: A longitudinal study during three years was conducted in 120 HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4:CD8 ratio, cardiovascular risk factor and antiretroviral (ARV) treatment and progression of subclinical atherosclerosis assessed using carotid IMT at baseline and after three years. RESULTS: Finally, 96 patients completed the study. Seventy-six (79.1%) patients were male, aged 44±10 years, 39 (40.6%) were on treatment with Protease inhibitors, 49 (51.04%) with non-nucleoside reverse transcriptase inhibitors (NNRTI), 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc and 2 (2.08%) only with nucleoside reverse transcriptase inhibitors (NRTI). The mean of ARV exposition was 6.9±5.9 years. Twenty six (27 %) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) hypertensive, 4 (4.16%) type 2 diabetes, 23 (23.9%) with dyslipidemia and 31 (32.3%) were infected with C hepatitis virus. Baseline IMT was significantly associated with age (rho=0.497; p<0.001), basal glucemia (rho=0.323; p=0.001), triglycerides (rho=0.232; p=0.023), Framingham score (rho=0.324; p=0.001), CD4:CD8 ratio (rho=-0.176; p=0.05) and dyslipidemia (0.72±0.16 mm vs 0.63±0.11 mm; p=0.029). In multivariable analysis where cardiovascular risk factor and ARV were included, IMT progression was inversely associated with CD4:CD8 ratio (OR=0.283; CI 95% 0.099-0.809; p=0.019) and treatment with NNRTI (OR=0.283; CI 95% 0.099-0.809; p=0.019). CONCLUSIONS: The inversion of CD4:CD8 ratio in treated HIV-infected patients is independently associated with IMT progression, a marker of age-associated disease. Therefore, it might be clinically useful as predictor of cardiovascular events. Surprisingly, there was a positive correlation between receiving NNRTI and progression of IMT.

Improvement of endothelial function after switching previously treated HIV-infected patients to an NRTI-sparing bitherapy with maraviroc.

INTRODUCTION: Nucleoside reverse transcriptase inhibitor (NRTI) is associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC) is an antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), a mediator of chronic inflammation and endothelial function. Our aim was to evaluate the maintenance of viral suppression and improvement of endothelial function in virologically suppressed HIV-infected patients switched to an NRTI-sparing combined antiretroviral therapy (cART) with MVC. MATERIALS AND METHODS: This observational, non-interventional, multicenter study was performed at the Infectious Diseases Service of Santa Lucia, Morales Meseguer, Virgen de la Arrixaca and Reina Sofía University Hospital (Murcia, Spain). The selection criteria were to be asymptomatic on a regimen with undetectable viral load (<50 HIV-RNA copies/mL) for at least six months, no previous treatment with R5 antagonists, no evidence of previous protease inhibitor (PI) failure and available R5 tropism test. Twenty-one HIV-infected patients were selected after the treatment regimen was changed to Maraviroc 150 mg/once daily plus ritonavir-boosted PI therapy. Endothelial function was prospectively evaluated through flow-mediated dilatation (FMD) of the brachial artery at baseline and at weeks 24. RESULTS: We included 21 patients on treatment with PI in combination with 2 NRTI. The mean cART exposition was 133±68.9 months. Fourteen (66.6%) were males, aged 49±9 years, 15 (71.4%) smokers, 4 (19.04%) family history of coronary heart disease, 1 (5.76%) type 2 diabetes and 3 (14.28%) hypertensive, mean total cholesterol was 185.5±35 mg/dL, c-LDL 100.2±37 mg/dL, tryglicerides 170.42±92.03 mg/dL, cHDL 52.6±15.5 mg/dL, CD4 779,5±383.28 cells/mL, nadir CD4 187,96±96 cells/mL. After 24 weeks of follow-up of a switch to an NRTI-sparing regimen, 95.2% of HIV-patients on viral suppressive cART maintained viral suppression and CD4+ T cell count. This cART switch improve endothelial function in patients with lower baseline FMD levels after 24 weeks (baseline FMD -1.19±4.84 % to 24 weeks FMD 11.32±7.27%; p=0.002). CONCLUSIONS: The results of our study show that a switch to an NRTI-sparing bi-therapy with MVC improves endothelial function and maintained the immune-virologic efficacy. This regimen emphasizes the needs for further clinical studies to associate these achievements with the incidence of non-AIDS-defining illnesses.

Síndrome opercular anterior epiléptico en un adulto / Epileptic opercular syndrome in an adult patient

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