K-Means Clustering Identifies Diverse Clinical Phenotypes in COVID-19 Patients: Implications for Mortality Risks and Remdesivir Impact.

INTRODUCTION: The impact of remdesivir on mortality in patients with COVID-19 is still controversial. We aimed to identify clinical phenotype clusters of COVID-19 hospitalized patients with highest benefit from remdesivir use and validate these findings in an external cohort. METHODS: We included consecutive patients hospitalized between February 2020 and February 2021 for COVID-19. The derivation cohort comprised subjects admitted to Hospital Clinic of Barcelona. The validation cohort included patients from Hospital Universitari Mutua de Terrassa (Terrassa) and Hospital Universitari La Fe (Valencia), all tertiary centers in Spain. We employed K-means clustering to group patients according to reverse transcription polymerase chain reaction (rRT-PCR) cycle threshold (Ct) values and lymphocyte counts at diagnosis, and pre-test symptom duration. The impact of remdesivir on 60-day mortality in each cluster was assessed. RESULTS: A total of 1160 patients (median age 66, interquartile range (IQR) 55-78) were included. We identified five clusters, with mortality rates ranging from 0 to 36.7%. Highest mortality rate was observed in the cluster including patients with shorter pre-test symptom duration, lower lymphocyte counts, and lower Ct values at diagnosis. The absence of remdesivir administration was associated with worse outcome in the high-mortality cluster (10.5% vs. 36.7%; p < 0.001), comprising subjects with higher viral loads. These results were validated in an external multicenter cohort of 981 patients. CONCLUSIONS: Patients with COVID-19 exhibit varying mortality rates across different clinical phenotypes. K-means clustering aids in identifying patients who derive the greatest mortality benefit from remdesivir use.

Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies.

Patients with herpes simplex virus (HSV) encephalitis (HSE) often develop neuronal autoantibody-associated encephalitis (AE) post-infection. Risk factors of AE are unknown. We tested the hypotheses that predisposition for AE post-HSE may be involved, including genetic variants at specific loci, human leucocyte (HLA) haplotypes, or the blood innate immune response against HSV, including type I interferon (IFN) immunity. Patients of all ages with HSE diagnosed between 1 January 2014 and 31 December 2021 were included in one of two cohorts depending on whether the recruitment was at HSE onset (Spanish Cohort A) or by the time of new neurological manifestations (international Cohort B). Patients were assessed for the type of neurological syndromes; HLA haplotypes; blood type I-IFN signature [RNA quantification of 6 or 28 IFN-response genes (IRG)] and toll-like receptor (TLR3)-type I IFN-related gene mutations. Overall, 190 patients (52% male) were recruited, 93 in Cohort A and 97 in Cohort B. Thirty-nine (42%) patients from Cohort A developed neuronal autoantibodies, and 21 (54%) of them developed AE. Three syndromes (choreoathetosis, anti-NMDAR-like encephalitis and behavioural-psychiatric) showed a high (≥95% cases) association with neuronal autoantibodies. Patients who developed AE post-HSE were less likely to carry the allele HLA-A*02 (4/21, 19%) than those who did not develop AE (42/65, 65%, P = 0.0003) or the Spanish general population (2005/4335, 46%, P = 0.0145). Blood IFN signatures using 6 or 28 IRG were positive in 19/21 (91%) and 18/21 (86%) patients at HSE onset, and rapidly decreased during follow-up. At Day 21 after HSE onset, patients who later developed AE had higher median IFN signature compared with those who did not develop AE [median Zs-6-IRG 1.4 (0.6; 2.0) versus 0.2 (-0.4; 0.8), P = 0.03]. However, a very high median Zs-6-IRG (>4) or persistently increased IFN signature associated with uncontrolled viral infection. Whole exome sequencing showed that the percentage of TLR3-IFN-related mutations in patients who developed AE was not different from those who did not develop AE [3/37 (8%) versus 2/57 (4%), P = 0.379]. Multivariate logistic regression showed that a moderate increase of the blood IFN signature at Day 21 (median Zs-6-IRG >1.5 but <4) was the most important predictor of AE post-HSE [odds ratio 34.8, interquartile ratio (1.7-691.9)]. Altogether, these findings show that most AE post-HSE manifest with three distinct syndromes, and HLA-A*02, but not TLR3-IFN-related mutations, confer protection from developing AE. In addition to neuronal autoantibodies, the blood IFN signature in the context of HSE may be potentially useful for the diagnosis and monitoring of HSE complications.

Diagnostic Performance of Six Rapid Antigen Tests for SARS-CoV-2.

Microbiological diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a challenge. Although real-time reverse transcription PCR (RT-PCR) represents the gold standard method, strategies that allow rapid and simple diagnosis are necessary for the early identification of cases. In this study, we evaluated the diagnostic performance of six different commercial rapid antigen tests (Coronavirus antigen [Ag] rapid test cassette [Healgen Scientific, Houston, TX, USA], COVID-19 Ag FIA [Vircell, SD Biosensor Inc., Gyeonggi-do, Republic of Korea], Clinitest rapid COVID-19 antigen test [Siemens, Healthineers, Erlangen, Germany], SARS-CoV-2 rapid antigen test [SD Biosensor; Roche Diagnostics, Basel, Switzerland], Panbio COVID-19 Ag rapid test device [Abbott, Chicago, IL, USA], and SARS-CoV-2 test [MonLab, Barcelona, Spain]) in 130 nasopharyngeal swab samples tested previously by RT-PCR. The overall sensitivity of the rapid tests ranged from 65% to 79%, and the specificity was 100% for all of them. The sensitivity was higher for those samples with RT-PCR cycle threshold (CT) values below 25 and those from patients presenting within the first week of symptoms. The Siemens test showed the highest sensitivity for patients with high viral loads while the Vircell test performed better than the rest for CT values of ≥25. IMPORTANCE The rapid detection of people infected with SARS-CoV-2 is essential for a correct and effective control of the disease it causes. This process must be sensitive, fast, and simple, and it must be possible to carry out in any type of health center. Rapid antigen tests are the answer to this need. Knowing its ability to detect the virus in different stages of the disease is essential for a correct diagnosis, which is why this study has been carried out to evaluate the sensitivity and specificity of 6 different antigens tests in nasopharyngeal smear samples.

Rapid detection of herpes simplex virus-1 from bronchoalveolar lavage fluids using loop-mediated isothermal amplification (LAMP) / Detección rápida del virus herpes simple-1 en lavado broncoalveolar mediante loop-mediated isothermal amplification (LAMP)

No disponible

Deleterious Effect of Steroids on Cytomegalovirus Infection Rate after Allogeneic Stem Cell Transplantation Depends on Pretransplant Cytomegalovirus Serostatus of Donors and Recipients.

This study examined the impact of prednisone (PDN) on cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (allo-SCT) according to donor and recipient CMV serostatus. Seventy-five patients underwent allo-SCT from June 2010 to July 2012. The risk of CMV infection according to donor and recipient serostatus was defined as follows: high risk (HR; D-/R+), intermediate risk (IR; D+/R+ and D+/R-), and low risk (D-/R-). Forty-five patients (60%) developed CMV infection, and 46 patients (61%) received steroids (PDN ≥ 1 mg/kg/day) to treat acute graft-versus-host disease. CMV infection was more common in those treated with steroids than in those not treated with steroids (70% versus 44%, respectively, P < .05). Overall, 40% of patients had recurrent CMV infection (50% PDN versus 24% no PDN, P < .05). Steroids had no impact on the incidence of CMV infection or its recurrence in HR patients; however, steroids did prolong the need for antiviral treatment. The incidence of CMV infection in IR patients was higher in those receiving PDN (80% PDN versus 41% no PDN, P = .01); recurrence rates were also higher (55% PDN versus 18% no PDN, P = .02). We analyzed CMV-specific immune reconstitution in the first 22 patients of the series and observed that patients on steroids had lower levels of CMV-specific lymphocytes TCD8 (P < .05 on days +60, +100, and +180) and that CMV-specific immune reconstitution (defined as lymphocytes CD8/IFN ≥ 1 cell/µL) was achieved later (after day +100 post-SCT) in the steroid group.

Definitive diagnosis in suspected Middle East Respiratory Syndrome Coronavirus cases.

We evaluated the microbiological diagnosis in 14 patients with epidemiological and clinical suspicion of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) attended in a non-endemic area between June 2015 and January 2017. While no MERS-CoV was detected, other respiratory viruses were identified in 12 cases and Mycoplasma pneumoniae in 1 case.

Angiopatía amiloidea cerebral, variante inflamatoria / Inflammatory variant of cerebral amyloid angiopathy

No disponible

Relación entre la actividad física y parámetros hemodinámicos en adultos / Relationship between physical activity and hemodynamic parameters in adults

Objetivo: Analizar la relación entre la actividad física, medida con acelerómetro, con índices de aumento central y periférico, y el grosor intima media (GIM) de carótida en adultos. Métodos: Se analizó a 263 pacientes incluidos en el estudio EVIDENT. La actividad física se evaluó con el acelerómetro Actigraph GT3X (counts/min) durante 7 días. La ecografía carotídea se utilizó para medir el grosor de íntima media de la carótida. El Sistema Sphygmo Cor se utilizó para medir el índice de aumento central y periférico (CAIx y PAIx). Resultados: Edad media 55,85 ± 12,21 años; 59,30% mujeres, índice de masa corporal 26,7 y presión arterial 120/77 mmHg. La actividad física media fue 244,37 counts/min. La media de tiempo dedicado a la actividad vigorosa o muy vigorosa fue 2,63 ± 10,26 min/día. Se observó una correlación inversa entre la actividad física y el PAIx (r = -0,179; p < 0,01), y entre el tiempo dedicado a la actividad vigorosa o muy vigorosa con el GIM (r = -0,174; p < 0,01), el CAIx (r = -0,217; p < 0,01) y el PAIx (r = -0,324; p < 0,01). Después de ajustar por diferentes factores de confusión, en el análisis de regresión múltiple se mantiene la asociación entre CAIx y la actividad física evaluada tanto con counts/min (p < 0,01) como con el tiempo dedicado a la actividad vigorosa o muy vigorosa (p < 0,01). Conclusiones: Los resultados indican que tanto la actividad física como el tiempo dedicado a la actividad vigorosa o muy vigorosa se asocian con el índice de aumento central en adultos

Objectives: To analyze the relationship between physical activity, as assessed by accelerometer, with central and peripheral augmentation index and carotid intima media thickness (IMT) in adults. Methods: This study analyzed 263 subjects who were included in the EVIDENT study. Physical activity was assessed during 7 days using the ActigraphGT3X accelerometer (counts/min). Carotid ultrasound was used to measure carotid IMT. The Sphygmo Cor System was used to measure central and peripheral augmentation index (CAIx and PAIx). Results: Mean age 55.85 ± 12 years; 59.30% female; 26.7 body mass index and blood pressure 120/77 mmHg. Mean physician activity counts/min was 244.37 and 2.63 ± 10.26 min/day of vigorous or very vigorous activity. Physical activity showed an inverse correlation with PAIx (r = -0.179; P<.01) and vigorous activity day time with IMT(r = -0.174; P<.01), CAIx (r = -0.217; P<.01) and PAIx (r =-0.324; P<.01). After adjusting for confounding factors in the multiple regression analysis, the inverse association of CAIx with counts/min and the time spent in vigorous/very vigorous activity was maintained. Conclusion: The results suggest that both physical activity and time spent in vigorous or vigorous activity are associated with the central augmentation index in adults

Monitorización ambulatoria de la presión arterial y actividad física en pacientes hipertensos / Ambulatory blood pressure monitoring and physical activity in hypertensive patients. Circadian pattern and physical activity

Objetivo: Analizar la relación entre el patrón circadiano de la presión arterial ambulatoria de 24h y la actividad física habitual en sujetos hipertensos. Material y métodos: Estudio transversal en el que se incluyeron 552 pacientes hipertensos del estudio EVIDENT (edad media 61 ± 55 años; 49,5% mujeres). La presión arterial ambulatoria se valoró con un tonómetro radial (dispositivo-B pro) y la actividad física se evaluó con un acelerómetro Actigraph GT3X (counts/minuto) durante 7días. Resultados: Los pacientes con patrón circadiano dipper realizaban mayor actividad física habitual que los no dipper. Las medidas de la actividad física (counts/minuto) presentaron correlación negativa con el ratio noche/día de las presiones arteriales sistólica y diastólica (ρ = -0,227 y ρ = -0,205; p < 0,001), respectivamente. Esta asociación se mantuvo en la regresión lineal múltiple después de ajustar por factores de confusión (β = -0,016; p < 0,001). En la regresión logística, considerando el patrón circadiano como variable dependiente (1: dipper; 0: no dipper), la odds ratio del tercer tertil de counts/minuto respecto del primero fue de 2,80 (IC95%: 1,73-4,51; p < 0,001) después de ajustar por las variables de confusión. Conclusiones: La actividad física evaluada con acelerómetro se asoció con un mayor descenso nocturno de la presión arterial y, en consecuencia, un menor ratio noche/día de la presión arterial sistólica y diastólica en sujetos hipertensos

Objective; To analyze the relationship between the circadian pattern of 24hour ambulatory blood pressure and regular physical activity in hypertensive patients. Material and methods: A cross-sectional study that included 552 hypertensive patients from EVIDENT study (mean age 61 ± 55 years, 49.5% women) was performed. Ambulatory blood pressure was measured with a radial tonometer (pro-B device) and physical activity was assessed with an accelerometer Actigraph GT3X (counts/min) for 7 days. Results: Patients with dipper circadian pattern performed more regular physical activity than non-dipper patients. The measures of physical activity (counts/min) showed negative correlation with the night/day systolic and diastolic blood pressures ratio (ρ = -.227 and ρ = -.205, P < .001), respectively. This association remained in the multiple linear regression after adjusting for confounders (β = -.016, P < .001). In the logistic regression, considering the circadian pattern as the dependent variable (1: dipper, 0: no dipper), the odds ratio for third tertile of counts/minute, compared to the first one was 2.80 (95% CI: 1.73-4.51, P < .001) after adjusting for confounding variables. Conclusions: Physical activity assessed by accelerometer was associated with increased nocturnal blood pressure and, consequently, a lower night/day systolic and diastolic blood pressure ratio in hypertensive patients

Loiasis ocular en paciente con hipereosinofilia crónica / Ocular loiasis in a patient with chronic hypereosinophilia

CASO CLÍNICO: Se presenta un caso de loiasis ocular con una filaria subconjuntival de 5,5 cm de longitud y una microfilaremia grave de una microfilaria/ml, en una paciente previamente asintomática, procedente de Guinea Ecuatorial, con antecedente de hipereosinofilia crónica en estudio. DISCUSSIÓN: La loiasis ocular es una infestación importada y poco frecuente en nuestro medio. No obstante, las parasitaciones crónicas procedentes de inmigrantes de zonas endémicas de África, pueden convertir la loiasis en una enfermedad emergente en nuestro medio

CASE REPORT: We present a case of ocular loiasis with a subconjunctival filaria, 5.5 cm long, and a severe microfilaremia, 1 microfilaria/ml, on a previously asymptomatic woman from Equatorial Guinea, with a past medical history of hypereosinophilia of unknown origin. DISCUSSIÓN: Ocular loiasis is an imported infestation with a very low rate in our country. Nevertheless, chronic infestation in immigrants coming from endemic areas of Africa may increase the rate of this disease in our country (AU)

El aumento de la velocidad de la onda de pulso no se asocia con la elevación de la presión arterial central en hipertensos con enfermedad renal / The increase in the speed of the pulse wave is not hypertensive patients with kidney disease

Objetivo: Analizar la relación entre la velocidad de la onda de pulso (VOP) y la presión arterial central valorada con el índice de aumento (IA) en personas hipertensas con enfermedad renal. Métodos: Se incluyeron 406 hipertensos con función renal normal y 72 con enfermedad renal. La rigidez arterial se estimó con la VOP y con el IA. Se siguieron los criterios de la Guía Europea de Hipertensión de 2007para valorar la existencia o no de enfermedad renal. Resultados: La VOP fue 8,98 ± 2,15 y 10,17 ± 3,01 m/s (p <0,05) y el IA 30,06 ± 12,46% y 30,23 ± 12,56% (p >0,05)en hipertensos con función renal normal y con enfermedad renal, respectivamente. El análisis de regresión múltiple reveló la función renal como determinante importante de VOP, pero no del IA. Conclusión: En hipertensos con enfermedad renal la VOP está aumentada, pero no el IA. Consideramos que el IA no es una medida fiable de la rigidez arterial en hipertensos con enfermedad renal (AU)

Objective: To analyze the relationship between pulse wave velocity (PWV) and central blood pressure evaluated by augmentation index (AIx) in hypertensive patients with kidney disease. Methods: 406 hypertensive patients with normal renal function and 72 with kidney disease. Arterial stiffness was estimated with the PWV and the AIx. We followed the 2007 European Guidelines of Hypertension criteria to assess the presence or absence of kidney disease. Results: PWV was 8.98 ±2.15 and 10.17 ± 3.01 m/s (p <0.05) and AIx 30.06% ± 12.46and 30.23% ± 12.56 (p >0.05) in hypertensive patients with normal renal function and kidney disease, respectively. Multiple regression analysis showed the renal function as an important determinant of PWV, but not AIx. Conclusion: In hypertensive patients with renal disease PWV is increased, but not the AIx. We believe that the AIx is not a reliable measure of arterial stiffness in hypertensive patients with kidney disease (AU)

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.

INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

pH- and photo-switched release of guest molecules from mesoporous silica supports.

This paper proposes a new nanoscopic molecular movable gate-like functional hybrid system consisting of nanoscopic MCM-41-based material functionalized onto pore outlets with a saccharide derivative capable of interacting with boronic acid functionalized gold nanoparticles (AuNPs) acting as nanoscopic caps. The gating mechanism involves the reversible reaction between polyalcohols and boronic acids to form boronate esters. Functionalized AuNPs thus act as a suitable nanoscopic cap via the reversible formation of the corresponding boroester bonds with the saccharide derivative anchored on the external surface of the mesoporous silica-based solid. The developed platform operates in aqueous solution and can be triggered by two simple external stimuli such as pH changes or light. The hydrolysis of the boroester bond takes place at pH 3, which results in rapid delivery of the safranine cargo from the pore voids into the aqueous solution. However, at pH 5 the pores are capped with nanoparticles and the delivery is strongly inhibited. The kinetics of the delivery was studied at pH = 3, assuming a simple diffusion process and that the kinetics of guest release from the pore voids of the hybrid material can be explained by the Higuchi model. It is possible to deliver the cargo in small portions by carrying out on-off aperture cycles via changing the pH from 3 to 5. AuNPs also open the possibility of employing light as a suitable stimulus for release procedures using the AuNPs' capacity for raising their temperature locally by absorption of laser light. The plasmonic heating using a Nd:YAG laser at 1064 nm results in the cleavage of the boronic ester linkage that anchors the nanoparticles to the surface of the mesoporous silica-based material, allowing the release of the entrapped guests. Further studies also demonstrated that it is possible to fine-tune the amount of cargo delivered by simply controlling the laser irradiation opening the possibility to designing laser-induced pulsatile release supports.

Chromo-fluorogenic sensing of pyrophosphate in aqueous media using silica functionalised with binding and reactive units.

A chromogenic chemosensor for selective pyrophosphate sensing in aqueous environments has been developed using silica functionalised surfaces.

Controlled release of vitamin B2 using mesoporous materials functionalized with amine-bearing gate-like scaffoldings.

A study on the controlled release of vitamin B(2) in pure water from mesoporous silica-based materials containing a pH- and anion-controlled nano-supramolecular gate-like ensembles built up by anchoring suitable polyamines on the external surface is reported (solid S1). This solid contains the vitamin (the delivered molecule) onto the pores, whereas the amine-based gate-like ensemble is anchored on the pore outlets. To obtain solid S1 the mesoporous MCM-41 support was first synthesized using tetraethyl orthosilicate (TEOS) as hydrolytic inorganic precursor and the surfactant hexadecyltrimethylammonium bromide (CTAB) as porogen species. Calcination of the mesostructured phase resulted in the starting solid. Then, first the vitamin and the latter an excess of 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane were added to the suspension containing the MCM-41 scaffolding and stirred. Solid S1 was characterized using standard solid state procedures. It was found that the functionalization process and the inclusion of the vitamin on the pores do not modify the mesoporous structure of the starting material. Delivery studies in water were carried out at pH 2 and 7. At pH 2 all the anions studied (sulfate, phosphate, GMP and ATP) strongly hinder vitamin release (C(anion)=1 x 10(-2) mol dm(-3)), whereas at pH 7 the delivery was observed for sulfate and GMP whereas the gate remained closed in the presence of ATP and phosphate. Selective delivery at neutral pH and no-liberation in acidic conditions can also be controlled with ATP and GMP using a suitable concentration of anion. The remarkable anion-controllable response of the gate-like ensemble at a certain pH can be explained in terms of anion complex formation with the tethered polyamines. Finally, selectivity patterns have been discussed in terms of kinetic rates of vitamin B(2) release. The pH-controlled gate-like scaffoldings on S1 might be a suitable prototype for the development of orally applicable delivery systems designed to have the particular ability to protect the cargo from the acidic conditions of the stomach (acid pH, gate closed) but will release the load at the intestine (basic pH, gate open).

Automated benthic counting of living and non-living components in Ngedarrak Reef, Palau via subsurface underwater video.

We introduce an automated benthic counting system in application for rapid reef assessment that utilizes computer vision on subsurface underwater reef video. Video acquisition was executed by lowering a submersible bullet-type camera from a motor boat while moving across the reef area. A GPS and echo sounder were linked to the video recorder to record bathymetry and location points. Analysis of living and non-living components was implemented through image color and texture feature extraction from the reef video frames and classification via Linear Discriminant Analysis. Compared to common rapid reef assessment protocols, our system can perform fine scale data acquisition and processing in one day. Reef video was acquired in Ngedarrak Reef, Koror, Republic of Palau. Overall success performance ranges from 60% to 77% for depths of 1 to 3 m. The development of an automated rapid reef classification system is most promising for reef studies that need fast and frequent data acquisition of percent cover of living and nonliving components.

Dual aperture control on pH- and anion-driven supramolecular nanoscopic hybrid gate-like ensembles.

The development of gate-like systems able to perform certain programmed functions is an interesting way of taking chemistry to the frontiers of nanoscience. In relation to this field, we report a complete study of the behavior of a pH-driven and anion-controlled nano-supramolecular gate-like ensemble obtained by anchoring suitable polyamines on the pore outlets of mesoporous materials of the type MCM-41 (solid N3-S). The release of an entrapped dye (Ru(bipy)3(2+)) from the pore voids into the bulk solution allows us to study the gating effect. A pH-driven open/close mechanism was observed that arises from the hydrogen-bonding interaction between amines at neutral pH (open gate) and Coulombic repulsions at acidic pH between closely located polyammoniums at the pore openings (closed gate). Molecular dynamics simulations using force field methods have been carried out to explain the pH-driven open/close mechanism. For this purpose, a mesoporous silica structure was constructed, taking as base the (111) plane of the beta-crystoballite structure on which large hexagonal nanopores and anchored polyamines were included. From these calculations, it was observed how completely unprotonated amines display poor coverage of the pore (fully open gate), whereas completely protonated amines (simulating a pH 2 or lower) result in a clear reduction of the pore aperture, in agreement with the experimental results. In additional to the pH-driven protocol, opening/closing of the gate-like ensemble can also be modulated via an anion-controlled mechanism. This study was carried out by monitoring the dye released from the pore voids of the N3-S solid at a certain pH in the presence of a range of anions with different structural dimensions and charges, including chloride, sulfate, phosphate, and ATP (C(anion) = 1 x 10(-2) mol dm(-3)). The choice of a certain anionic guest results in a different gate-like ensemble behavior, ranging from basically no action (chloride) to complete (ATP) or partial pore blockage, depending on the pH (sulfate and phosphate). The remarkable anion-controllable response of the gate-like ensemble can be explained in terms of anion complex formation with the tethered polyamines. These experimental studies are also in agreement with computational simulations with fluoride, chloride, iodide, and dihydrogen phosphate anions. In the model, larger anions push the tethered polyamines toward the pore openings more efficiently, and therefore the pore aperture decreases. The studies also show that, for anions showing a strong tendency to form hydrogen-bonding networks (e.g., phosphate), complete pore blockage was observed at acidic pH. Finally, selectivity patterns have been discussed in terms of kinetic rates of the liberation of the Ru(bipy)3(2+) dye from the amine-functionalized dye-containing material N3-S.

Optimización del uso de Agentes estimulantes del Receptor de la Eritropoyetina (AREs) en pacientes con neoplasias hematológicas basado en el nivel de hemoglobina reticulocitaria / Optimizing the use of Erythropoietin-Receptor stimulating Agents (ERAs) in patients with hematopoietic malignancies based on the level of reticulocyte hemoglobin

Los agentes estimulantes del Receptor de la Eritropoyetina (AREs) se usan en el tratamiento de la anemia de hemopatías malignas (HM). Sin embargo, la tasa de respuestas es variable por diversos factores como el déficit funcional de hierro (DFF). El nivel de hemoglobina (Hb) reticulocitaria es un parámetro fácil de obtener que ha mostrado su utilidad en el diagnóstico del DFF. El objetivo de este estudio fue identificar qué pacientes con HM tratados con AREs presentan DFF y si la Hb reticulocitaria predice la respuesta hemoglobínica en estos enfermos. Se incluyeron 42 pacientes con diagnostico de Mieloma Múltiple (n=17), Linfoma no Hodgkin (n=14), Linfoma de Hodgkin (n=3), Leucemia Linfática Crónica (n=4), Síndrome Mielodisplásico (n=2), Leucemia Linfoblástica Aguda (n=1) y Leucemia Mieloblástica Aguda (n=1). Veinticinco fueron tratados con Epoetina-beta, diez y seis con Darbepoetina y uno con Epoetina alfa.La respuesta fue favorable en el 28%, 53% y 58% de lospacientes a las 3, 6 y 12 semanas de tratamiento, respectivamente. Se detectó DFF en el 17% de los pacientes. En cuanto a la respuesta, no hubo diferencias estadísticamente significativas entre los pacientes con y sin DFF, si bien, a mitad de tratamiento, fue ligeramente superior en el grupo sin DFF (57% vs 43%, p>0.05). El nivel basal de Hb reticulocitaria se correlacionó con el grado de respuesta global a las 12 semanas de finalizar el tratamiento. Así, el 79% de los pacientes respondedores tenían una Hb reticulocitaria inicial >36·5 pg, mientras que este porcentaje bajó al 30% en los no respondedores (p = 0.024)En resumen, la Hb reticulocitaria es un método sensible ypreciso para detectar DFF en pacientes con HM bajo tratamiento con AREs. Además, un nivel elevado de Hb reticulocitaria basal es un parámetro que se asocia con respuesta favorable al tratamiento

The Erythropoietin-Receptor stimulating Agents (ERAs) areindicated in the supportive treatment of the anemia in hematological malignancies (HM). However, the response rate is variable due to factors such as the functional iron deficiency (FID). The level of the reticulocyte hemoglobin (RHb) is an easy-to-obtain parameter very useful for the diagnostic of the FID.The purpose of this study was to evaluate which patientswith HM treated with ERAs present FID. In addition, wetried to asses if the level of RH predicts the response in these patients.We included 42 patients with the following diagnostics:Multiple Myeloma (n= 17), Non Hodgkin Lymphoma(n=14), Hodgkin Lymphoma (n=3), Chronic lymphocyticLeukemia (n=4), Myelodisplastic syndrome (n=2), Acutelymphoblastic Leukemia (n=1), and Acute mieloblasticLeuKemia (n=1). Twenty five of them were treated withEpoetin beta, sixteen with darbepoetin alfa and one withEpoetin alfa at standard doses. The response was favorable in 28%, 53% and 58% of patients at the third, sixth and twelfth week of the treatment, respectively. FID was detected in 17% of the patients. Theresponse rate was not statistical significant different between patients with and without FID, although it was slightly superior in the group without FID (57% vs. 43%, p>0.05). Seventy nine percent of patients with a favorable response at twelve weeks showed an initial RH >36·5 pg, while this percentage was only 30% in patients who did not respond (p=0.024).In conclusion, RH is a sensitive and specific method to detect FID in patients with HM who are treated with ERAs.Furthermore, the high level of RH at the baseline is a predictor of favorable response of treatment, in these patients