Khinchin Families, Set Constructions, Partitions and Exponentials.

In this paper, we give a simple criterion to verify that functions of the form eg are in the Hayman class when g is a power series with nonnegative coefficients. Thus, using the Hayman and Báez-Duarte formulas, we obtain asymptotics for the coefficients of generating functions that arise in many examples of set construction in analytic combinatorics. This new criterion greatly simplifies the one obtained previously by the authors.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

Insights on the catalytic behaviour of sulfonic acid-functionalized ionic liquids (ILs) in transesterification reactions - voltammetric characterization of sulfonic task-specific ILs with bisulfate anions.

This work shows for the first time the link between the amount of free sulfuric acid (as detected by cyclic voltammetry) and the activity of sulfonic-acid-functionalized ionic liquids (ILs) as acid catalysts for a transesterification reaction, and demonstrates that sulfonic acid groups, while are not directly involved in the catalysis, release the free acid during the reaction. Two imidazolic ILs with bisulfate as the counterion and their corresponding task-specific ILs (TSILs) that resulted from the addition of a sulfonic acid group inside the imidazolic-base structure were studied. The outstanding catalytic activity at room temperature of the TSILs 1-(4-sulfonic acid)-butyl-3-methylimidazolium bisulfate ([bsmim]HSO4) and 1-(4-sulfonic acid)-butyl-imidazolium bisulfate ([bsHim]HSO4) for the transesterification of p-nitrophenyl acetate with methanol was associated to the significant amounts of free sulfuric acid in equilibria with the ionic pairs. It was concluded that these TSILs function as reservoirs for releasing the free acid, which is the actual acid catalyst. In contrast, the corresponding non-sulfonic ILs supply very little amounts of free acid and consequently present low catalytic activities at room temperature, which in fact can be improved by increasing the reaction temperature up to 100 °C.

Model-Based Systems Engineering Applied to Trade-Off Analysis of Wireless Power Transfer Technologies for Implanted Biomedical Microdevices.

Decision-making is an important part of human life and particularly in any engineering process related to a complex product. New sensors and actuators based on MEMS technologies are increasingly complex and quickly evolving into products. New biomedical implanted devices may benefit from system engineering approaches, previously reserved to very large projects, and it is expected that this need will increase in the future. Here, we propose the application of Model Based Systems Engineering (MBSE) to systematize and optimize the trade-off analysis process. The criteria, their utility functions and the weighting factors are applied in a systematic way for the selection of the best alternative. Combining trade-off with MBSE allow us to identify the more suitable technology to be implemented to transfer energy to an implanted biomedical micro device.

Detection of DNA damage in pigeon erythrocytes using a chromatin dispersion assay.

The monitoring of environmental genotoxicity requires the selection of model organisms as 'sentinels' as well as the development of sensitive and reliable tests for the assessment of DNA damage. The aims of this study were to quantify genomic DNA strand breakage in the erythrocytes of Columba livia induced by thermal stress using the modified chromatin dispersion test and to validate the results by alkaline comet assay and DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). The chromatin dispersion test allowed for clear visualization of erythrocyte cells with DNA damage and of cells with no DNA damage. DNA damage increased significantly with increase in temperature. Additionally, we observed nuclear abnormalities associated with apoptosis, such as karyorrhexis (nuclear disintegration) and karyolysis (nuclear dissolution). These results were validated by alkaline comet assay and DBD-FISH. In conclusion, this procedure is a reliable, precise, and inexpensive morphological bioassay for routine quantitative analysis of DNA breakage in pigeon erythrocytes induced by thermal stress. This method could also be useful as a practical screening tool for genotoxicity testing in environmental care.

Post-Synthetic Modification of ZIF-8 Crystals and Films through UV Light Photoirradiation: Impact on the Physicochemical Behavior of the MOF.

The physicochemical modification of Metal-Organic Frameworks (MOFs) is a current challenge in the search to improve their performance in different technological applications. In this work we analyze the post-synthetic modification of ZIF-8 crystals and films through a simple and clean treatment that involves the exposure to a UV lamp under environmental conditions. It is demonstrated that a short treatment alters the MOF structure and chemistry, providing a modified ZIF-8 due to partial disconnections of its structure which increase the amount of terminal surface species such as Zn-OH and -C=N-H, but without compromising the overall MOF structure, specific surface area or thermal stability. Additionally, it leads to changes in several properties of the ZIF-8, such as its capacity to accumulate charge through pseudocapacitive processes, its interaction with nitric oxide and its light absorption behavior. This strategy of modifying ZIF-8 without the use of chemicals through a gentle disconnection of its own structure could open new perspectives of post-functionalization of crystals and films of ZIF-8 to be used in a wide range of applications.

Compact and efficient gas diffusion electrodes based on nanoporous alumina membranes for microfuel cells and gas sensors.

This work describes the fabrication, characterization and evaluation of thin gas diffusion electrodes (GDEs) that are capable of electrocatalyzing the reaction of dissolved gases operating at high diffusion limiting current densities and with fast response times. Nanoporous alumina membranes (NAMs) were used as supports of metal electrocatalysts. NAMs were hydrophobized by silanization and coated on one side with Pt, either over the whole alumina surface by sputtering or just onto the pore openings by local chemical deposition. The Pt-modified NAM-based GDEs were evaluated for hydrogen oxidation. They operated by exposing their coated side to the electrolyte solution and the hydrophobic uncoated side to the flowing gas. Due to the NAM hydrophobicity, flooding of the pores by the electrolyte was diminished, so they were quickly filled by the circulating gas. Simulations of the process on single-pore GDEs showed that the dissolved gas diffused into the solution both radially (ideal pore) and linearly (partially flooded pore), reaching the electrocatalyst film placed right around the pore, which guaranteed a fast mass transport. Hydrogen oxidation operated on these NAM-based GDEs at a steady state with limiting current densities as high as 0.5 A cm-2, which were attained in less than 5 s and were proportional to H2 concentrations over a wide range. Thus, their potential use in microfuel cells and gas sensors was demonstrated.

CCL2 shapes macrophage polarization by GM-CSF and M-CSF: identification of CCL2/CCR2-dependent gene expression profile.

The CCL2 chemokine mediates monocyte egress from bone marrow and recruitment into inflamed tissues through interaction with the CCR2 chemokine receptor, and its expression is upregulated by proinflammatory cytokines. Analysis of the gene expression profile in GM-CSF- and M-CSF-polarized macrophages revealed that a high CCL2 expression characterizes macrophages generated under the influence of M-CSF, whereas CCR2 is expressed only by GM-CSF-polarized macrophages. Analysis of the factors responsible for this differential expression identified activin A as a critical factor controlling the expression of the CCL2/CCR2 pair in macrophages, as activin A increased CCR2 expression but inhibited the acquisition of CCL2 expression by M-CSF-polarized macrophages. CCL2 and CCR2 were found to determine the extent of macrophage polarization because CCL2 enhances the LPS-induced production of IL-10, whereas CCL2 blockade leads to enhanced expression of M1 polarization-associated genes and cytokines, and diminished expression of M2-associated markers in human macrophages. Along the same line, Ccr2-deficient bone marrow-derived murine macrophages displayed an M1-skewed polarization profile at the transcriptomic level and exhibited a significantly higher expression of proinflammatory cytokines (TNF-α, IL-6) in response to LPS. Therefore, the CCL2-CCR2 axis regulates macrophage polarization by influencing the expression of functionally relevant and polarization-associated genes and downmodulating proinflammatory cytokine production.

Theory and experiments for voltammetric and SECM investigations and application to ORR electrocatalysis at nanoelectrode ensembles of ultramicroelectrode dimensions.

Theoretical and experimental approaches to characterizing nanoelectrode (NE) ensembles of ultramicroelectrode dimensions (UME-NEEs) as a function of fraction of active area and random NE distribution are described. UME-NEEs were fabricated by addressing microregions of a gold-filled polycarbonate membrane through the UMEs of an underlying microfabricated addressable array. Results of Comsol Multiphysics 3D simulations based on randomly spaced NEs of 15 nm radius on a UME disk geometry of radii up to 5 µm are shown for steady-state voltammetry (SSV) and scanning electrochemical microscopy (SECM) experiments. Analytical equations were developed to describe the diffusion-limited steady-state current and steady-state voltammogram at an UME-NEE. These equations are shown to be in good agreement with the simulations and enabled evaluation of experimental SSVs. Comparison of experimental and simulated SECM approach curves, images, and tip voltammograms enabled the fraction of active area and distribution of NEs to be visualized and determined for individual UME-NEEs. Gold UME-NEEs are shown to be unique platforms for electrodeposition in forming nanoparticle electrodes (UME-NPEs). Electrocatalysis results for the oxygen reduction reaction (ORR) on Pt UME-NPEs in 0.1 M H2SO4 are also shown.

Development, characterization, and evaluation of the antioxidant activity of nanocarriers based on surfactant swollen micelles that encapsulate essential oils.

This work aimed to compare the performance of two relatively underexplored methods for the swollen micelles (SMs) production as nanocarriers for essential oils (EOs). Origanum vulgare and Thymus vulgaris EOs were examined. The first method (SMs-1), involved a self-assembly process, while the second one (SMs-2), employed titration operation of an emulsion into a surfactant solution for SMs formation. Tween 80 and ethanol were used as surfactant and co-surfactant, respectively. The solubilization kinetics and the saturation concentration of EOs were determined. Particle size (measured by DLS) and encapsulation efficiency (EE) were the control parameters assessed, along with the EOs-loaded SMs' stability during 30 days of storage. Additionally, the EOs-loaded SMs' morphology was analyzed using atomic force microscopy (AFM). Finally, the antioxidant activity through the ABTS+ radical scavenging and the reducing power of EOs encapsulated in SMs was determined. The results showed that the solubilization of EOs in SMs was a rapid process with high EE. EOs-loaded SMs-2 systems exhibited greater colloidal stability and higher EE compared to EOs-loaded SMs-1 systems, showing smaller and more homogeneous particle sizes. Moreover, EOs-loaded SMs-2 systems maintained constant EE throughout the storage period. AFM imaging confirmed the rounded and heterogeneous morphology of EOs-loaded SMs-1 and the smaller, more homogeneous, and spherical morphology of EOs-loaded SMs-2. EOs-loaded SMs-2 showed high ABTS+ radical scavenging and reducing power when encapsulated in SMs. In conclusion, the SMs-2 method emerged as an effective approach for producing efficient nanocarriers for EOs, signifying a promising path for future developments in antioxidant delivery systems.

DBD-FISH Using Specific Chromosomal Region Probes for the Study of Cervical Carcinoma Progression.

Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.

Investigating silent strokes in hypertensives: a magnetic resonance imaging study (ISSYS): rationale and protocol design.

BACKGROUND: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline.Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined.ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. METHODS/DESIGN: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia.On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed.Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors. DISCUSSION: Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.

Chromatin Dispersion Test to Asses DNA Damage in Cervical Epithelial Cells.

The chromatin dispersion test (CDT) is based on the removal of nuclear proteins under the assumption that cells with fragmented DNA produce a typical halo of circular DNA loops, which is absent in cells with non-fragmented DNA. This method represents a simple, rapid, accurate, highly reproducible, and inexpensive technique to assess nuclear DNA damage in somatic cells. The visualization of DNA damage and the capacity of the test to provide a threshold value to discriminate between high and low levels of cervical lesions would aid in determining the malignant transformation. All of these advantages associated with the CDT protocol could promote this technique as a tool for the quick and reliable diagnosis of cervical epithelial disorders, even at primary-care centers.

The Impact of Clinical Training Seminars on Stress and Perception of Clinical Placement Stressors among Spanish Undergraduate Nursing Students: A Two-Phase Mixed-Methods Study.

Stress and stressors related to clinical practice are some of the main reasons for the discomfort reported by nursing students. It is important to identify the causes of stress and seek strategies to reduce the stress levels in nursing students. Clinical training seminars have proven to be a useful tool to reduce stress levels. This study aims to evaluate the effects of a series of clinical training seminars on the levels of stress and perception of stress factors before the start of clinical practice among undergraduate Spanish nursing students. A two-phase, sequential mixed-methods design was used. For the quantitative phase, data were collected using Cohen's Perceived Stress Scale and the KEZKAK questionnaire before and after the clinical training seminars. Qualitative data were collected through a focus group session held after the clinical training period. The results show a significant reduction (p = 0.002) in perceived stress levels after the clinical training seminars, and also a change in students' perception of stressors in the clinical placement. This study provides valuable information for the development of content for clinical training seminars. Universities should develop strategies to reduce stress in their students caused by the clinical placement.

Time to seeking emergency department care for asthma: self-management, clinical features at presentation, and hospitalization.

OBJECTIVES: Understanding the events preceding emergency department (ED) asthma visits can guide patient education regarding managing exacerbations and seeking timely care. The objectives of this analysis were to assess time to seeking ED care, self-management of asthma exacerbations, and clinical status on presentation. METHODS: A total of 296 patients was grouped according to time to seeking ED care: ≤1 day (22%), 2-5 days (44%), and >5 days (34%) and was compared for clinical and psychosocial characteristics. Asthma severity at presentation was obtained from patient report with the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ) and from physicians' ratings using decision to hospitalize as an indicator of worse status. RESULTS. Mean age was 44 years, 72% were women, 10% had been in the ED in the prior week, and 28% came to the ED by ambulance. Patients who waited longer were more likely to be older, have more depressive symptoms, and have been in the ED in the prior week. They also were more likely to have taken more medications, but they were not more likely to have visited or consulted their outpatient physicians. Patients who waited longer reported worse ACQ (p < .0001) and AQLQ (p = .0002) scores and were more likely to be hospitalized for the current exacerbation (odds ratio 1.9, 95% CI 1.1, 3.2, p = .03). CONCLUSIONS: Patients who waited longer to come to the ED had worse asthma on presentation, had more functional limitations, and were more likely to be hospitalized. The ability to gauge severity of exacerbations and the use of the ED in a timely manner are important but often overlooked are self-management skills that patients should be taught.

History of symptom triggers in patients presenting to the emergency department for asthma.

OBJECTIVES: Understanding triggers is important for managing asthma particularly for patients who seek emergency department (ED) care for exacerbations. The objectives of this analysis were to delineate self-reported triggers in ED patients and to assess associations between triggers and asthma knowledge, severity, and quality of life. METHODS: At the time of an ED visit, 296 patients were asked what were their usual asthma triggers based on a checklist of 25 potential items, and what they thought specifically precipitated their current ED visit. Using standardized scales, patients also were asked about asthma knowledge, severity, and quality of life. RESULTS: The mean age was 44 years and 72% were women. Patients cited a mean of 12 triggers; most patients had diverse triggers spanning respiratory infections, environmental irritants, emotions, allergens, weather, and exercise. Patients with more triggers were more likely to be women (odds ratio (OR) = 2.0, confidence interval (CI) = 1.3, 3.2, p = .002), obese (OR = 1.7, CI = 1.1, 2.5, p = .01), and to not have a smoking history (OR = 1.9, CI = 1.3, 2.9, p = .001). There were no associations between number of triggers and current age, age at diagnosis, education, socioeconomic status, or race/ethnicity. Patients who cited more triggers had more frequent flares (OR = 1.1, CI = 1.1, 1.2, p < .0001), worse quality of life scores (OR 1.6, CI = 1.1, 2.4, p = .02), and were more likely to have been previously hospitalized for asthma (OR = 1.9, CI = 1.3, 2.9, p = .003) and to have previously required oral corticosteroids (OR = 2.9, CI = 1.6, 5.1, p = .003). There was little clustering of specific triggers according to the variables we considered except for more frequent animal allergy in patients diagnosed at a younger age (OR = 2.8, CI = 1.7, 4.5, p < .0001) and worse quality of life in patients citing emotional stress as a trigger (OR = 2.5, CI = 1.5, 4.0, p = .0002). Patients attributed their current ED visit to multiple precipitants, particularly respiratory infections and weather, and these were concordant with what they reported were known triggers. CONCLUSIONS: Patients presenting to the ED for asthma reported multiple triggers spanning diverse classes of precipitants and having more triggers was associated with worse clinical status. ED patients should be instructed that although it may not be possible to eliminate all triggers, mitigating even some triggers can be helpful.

Resilience and entrepreneurial intentions of people with disabilities: in search of the Sustainable Development Goals (SDGs).

Background: There is a significant gap in employment between people with and without disabilities, despite the importance of work in achieving their independence, autonomy, and integration into society. There are several reasons that cause this gap to exist, such as: people with disabilities feel less prepared, there is a stigma or discrimination to hire people with disabilities and the incompatibility of schedules due to medical issues, among others. That is why entrepreneurship emerges as a good option for the integration of people with disabilities in our society, improves their confidence and promotes some of the Sustainable Development Goals set out in the 2030 Agenda. According to existing literature, people with disabilities have certain virtues such as resilience and motivation that favor entrepreneurship. Thus, the purpose of this study is to provide new insights into the variables that determine the entrepreneurial intention of people with disabilities. Methods: In order to respond to this objective, an online questionnaire was given to people with disabilities between the ages of 16 and 65 years, residing in diverse regions of Spain. To analyze the results, this study uses Partial Least Squares-Structural Equation Modeling (PLS-SEM) in a sample of 235 people with disabilities in Spain using as a framework Krueger´s improved model, adding resilience as a new variable. Results: The results reflect the importance of resilience, the subjective norm, and perceived collective efficacy in the entrepreneurial processes of people with disabilities. Conclusions: This study contributes to the underdeveloped literature on entrepreneurship in people with disabilities; it provides insights that can have a practical effect on the reduction of the inequality gap between people with and without disabilities making recommendations to clinicians, vocational psychologists, and policymakers; also, this study would advance the achievement of Sustainable Development Goals 8 and 10.

Soluble Triggering Receptor on Myeloid Cell-1 and its Predictive Factors in Patients With End-Stage Kidney Disease on Hemodialysis.

Triggering receptor expressed on myeloid cells (TREM)-1 is a potent and early amplifier of the inflammatory response expressed on neutrophils and monocytes/macrophages. TREM-1, and its soluble form (sTREM-1), are increased in sepsis and other noninfectious inflammatory conditions. However, virtually no data are available in kidney disease. To determine serum sTREM-1 and its associated variables in patients on hemodialysis (HD), cross-sectional study including 264 HD patients and 148 controls. sTREM-1 was measured by quantitative sandwich enzyme immunoassay; soluble tumor necrosis factor receptor-1 (sTNF-R1), interleukin-6 (IL-6), and C-reactive protein (CRP) were also measured. All inflammation markers were significantly higher in HD patients than controls. Median (IQR) sTREM-1 was 1,006 (613-1,650) pg/mL but undetectable in controls. Considering only HD patients, sTREM-1 was positively correlated with IL-6 (r = 0.19, p = 0.008), and its levels were significantly higher in patients with arteriovenous fistula than in those with temporary catheter (1,226 vs. 743 pg/mL), in patients with 3 HD sessions/week than in those with 2 sessions/week (1,150 vs. 646 pg/mL), and in patients with >1 year on HD than in those with ≤1 year (1,100 vs. 948 pg/mL), whereas they were not different regarding age or presence of infection. Serum sTREM-1, sTNF-R1, IL-6, and CRP were higher in HD patients compared to controls. In HD patients, sTREM-1 displayed higher levels in individuals with arteriovenous fistula, 3 sessions/week and longer vintage, but not in those with infection or older age; in multivariate analysis, only the first two variables significantly predicted higher sTREM-1 levels.

Fibrosis quística: patogenia bacteriana y moduladores del CFTR (regulador de conductancia transmembranal de la fibrosis quística).

Cystic fibrosis is an autosomal recessive inherited disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR is a protein that transports ions across the membrane of lung epithelial cells. Loss of its function leads to the production of thick sticky mucus, where various bacterial pathogens can establish and adapt, contributing to the gradual loss of lung function. In this review, evidence of the molecular mechanisms used by Pseudomonas aeruginosa and Burkholderia cenocepacia to survive and persist in the pulmonary environment will be provided. Additionally, new therapeutic strategies based on CFTR function modulators will be described.

La fibrosis quística es una enfermedad hereditaria autosómica recesiva que se origina por mutaciones en el gen regulador de conductancia transmembranal de la fibrosis quística (CFTR, cystic fibrosis transmembrane conductance regulator). El CFTR es una proteína que transporta iones a través de la membrana de las células epiteliales pulmonares. La pérdida de su función conlleva la producción de un moco pegajoso y espeso, donde se pueden establecer y adaptar diversos patógenos bacterianos que contribuyen a la pérdida gradual de la función pulmonar. En este artículo de revisión se dará evidencia de los mecanismos moleculares que utilizan Pseudomonas aeruginosa y Burkholderia cenocepacia para sobrevivir y persistir en el ambiente pulmonar. Adicionalmente, se describirán las nuevas estrategias de terapia a base de moduladores de la función del CFTR.

Randomized, double-blinded, controlled clinical trial of the effect of captopril, telmisartan and their combination on systemic inflammation of patients on hemodialysis.

To evaluate individual and combined effect of captopril and telmisartan on systemic inflammation markers of hemodialysis (HD) patients. Randomized, double-blinded, controlled clinical trial. Patients on HD at least 2 months, with arteriovenous fistula, were randomly allocated to groups: (1) captopril/placebo (N 13); (2) telmisartan/placebo (N 13); (3) captopril + telmisartan (N 12); or (4) placebo/placebo (N 12). During 3 months, patients received oral drugs as follows: captopril 50 mg/day, telmisartan 80 mg/day or placebo. Patients excluded if they had conditions or were on drugs potentially influencing on inflammation. Clinical and biochemical evaluations were performed monthly. Serum tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured at 0, 1 and 3 months. Baseline, demographic, clinical and biochemical variables were comparable between groups. Baseline versus final inflammatory markers were: captopril/placebo TNFα, 2.47 (0.1-4.5) versus 1.73 (0.3-3.8) pg/ml; IL-6, 17.03 (7.2-23) versus 7.90 (0.7-19) pg/ml; CRP, 4.21 (1.6-18) versus 5.9 (3.0-28) mg/l; telmisartan/placebo TNFα, 3.03 (2.3-4.6) versus 1.70 (1.2-2.0) pg/ml; IL-6, 14.10 (5.5-23) versus 9.85 (6.2-13) pg/ml; CRP, 5.74 (2.1-13) versus 10.60 (1.5-27) mg/l; captopril + telmisartan TNFα, 1.43 (0.7-5.4) versus 0.40 (0.1-2.1) pg/ml; IL-6, 10.05 (4.9-23) versus 4.00 (0.7-7.7) pg/ml (p < 0.05); CRP, 3.26 (0.7-12) versus 2.83 (0.6-6.5) mg/l; placebo/placebo TNFα, 3.13 (1.6-5.6) versus 1.64 (1.6-2.3) pg/ml; IL-6, 8.12 (5.4-16) versus 7.60 (2.4-15) pg/ml; CRP, 5.23 (1.9-16) versus 3.13 (1.5-18) mg/l. Monotherapy with captopril or telmisartan display a trend, but their combined treatment significantly decreased serum levels of IL-6. No remarkable changes on TNFα and CRP were observed.