Caracterización de los fagos de Klebsiella pneumoniae con potencial biotecnológico

The extensive use and misuse of antibiotics has led to an increased emergence of multidrug-resistant Klebsiella pneumoniae strains. They are a serious concern worldwide due to their propensity to spread and the scarce effective treatments left. Consequently, phage therapy is garnering renewed interest as an alternative method to defeat antibiotic resistant bacteria. Phages – natural pathogens of bacteria – have several properties: high capacity to replicate and host specificity that turns them into a great advantage over antibiotics. Eight bacteriophages infecting Klebsiella pneumoniae were characterized according to their genetic material and morphology by performing endonuclease digestions and transmission electron microscopy imaging with 1% phosphotungstic acid or 2% uranyl acetate as staining dyes. Then, they were classified in agreement with their morphological characterization. Seven phages (EKP3P1, EKP3P2, EKP3P4, EKP3P5, EKP8P2, EKP8P3 and EKP8P4) were classified into Siphoviridae family showing hexagonal heads with long non- contractile, sometimes flexible tails and closely related restriction patterns. EKP8P1 phage was classified into Podoviridae family showing an icosahedral head with a short non-contractile tail and a different restriction pattern. They all belong to Caudovirales order. Moreover, a prophage was found in EKP8P1 sample, and classified into Siphoviridae family according to its morphology. The genome of EKP3P5 phage, a double stranded DNA of 47,622 bp long, was sequenced and annotated manually. EKP3P5 phage is a temperate phage encoding integrase, holin and endolysin proteins, among others. Therefore, EKP3P5 could not be used in phage therapy due to the risk of transferring virulence and resistance genes to the host bacteria. For all the above reasons, this thesis provides detailed knowledge of the physical structure along with genomic qualities of eight bacteriophages infecting multidrug- resistant Klebsiella pneumoniae strains. This is important for determining the potential of phages as therapeutic agents and the first step to improve phage therapy

Feasibility of computerized adventitious respiratory sounds to assess the effects of airway clearance techniques in patients with bronchiectasis

Objective: To examine the feasibility of adventitious respiratory sound (ARS) as an outcome measure to assess the effects of airway clearance techniques (ACTs) in outpatients with bronchiectasis. Methods: ARS were registered pre/post four ACTs sessions. Clinical outcomes included: number of crackles (coarse and fine), number of wheezes (monophonic and polyphonic), wheezes occupation rate (%) and sputum quantity. Feasibility outcomes of ARS included: reasons for exclusion, suitability, safety, equipment and time required, magnitude of change after intervention and sample size estimation. Results: Seven patients (49.7 ± 20.5 years; FEV1 69.3 ± 15.8% predicted) were included. Recordings from four patients were excluded due to excessive environment noise. All ARS measurements were completed without any adverse events. An electronic stethoscope was acquired and the time spent to complete each assessment was 6 ± 3.5 min. The largest changes were observed for number of expiratory coarse crackles [effect size (95%CI) ES = 0.40 (0.01–0.79)], which correlated moderately with sputum quantity (r = 0.56), and inspiratory monophonic wheezes [ES = 0.61 (0.22–1.00)]. The estimated sample size for a full crossover trial was 46. Conclusions: ARS is feasible to assess the effects of ACTs in patients with bronchiectasis. Expiratory coarse crackles seem to be the most appropriate ARS parameter, but this finding needs to be confirmed in an adequately powered trial.publishe

Highly uniform Y3Al2Ga3O12-based nanophosphors for persistent luminescence bioimaging in the visible and NIR regions

In the last few years, persistent phosphors with a garnet crystal structure have attracted a great deal of interest for a plethora of applications ranging from bioimaging to anti-counterfeiting technologies. However, the development of synthesis methods to fabricate uniform garnet-based micro and nanoparticles, that are needed for such applications, is not mature at all. This study reports the synthesis of highly uniform yttrium aluminum gallium garnet nanospheres. The method is based on homogeneous precipitation in a polyol medium followed by silica coating and calcination. The nanoparticles resulting after silica removal were also uniform and were easily functionalized with polyacrylic acid. The colloidal stability of the latter in physiological media and their biocompatibility were analyzed. The luminescence of the particles, doped with Ce3+, Cr3+, and Nd3+, was studied by recording emission and excitation spectra and persistent luminescence decay curves. Due to their uniform morphology, high colloidal stability, absence of toxicity, and persistent emission in the visible and near-infrared regions, the reported nanospheres show great potential as persistent luminescent bioimaging probes. In addition, the synthesis method paves the way for future use of this persistent material in other applications that require the phosphor to be in the form of highly uniform nanoparticles

Impact of Hypertonic Saline Solutions on Sputum Expectoration and Their Safety Profile in Patients with Bronchiectasis: A Randomized Crossover Trial

Background: The role of hyaluronic acid plus hypertonic saline (HA+HS) as a mucoactive treatment in patients with bronchiectasis is still unknown. This study evaluated whether HA+HS solution enhances similar sputum quantity with better safety profile than HS alone in patients with bronchiectasis. Methods: In this double-blind randomized crossover trial, three solutions (7% HS; 0.1% HA +7%HS; and 0.9% isotonic saline, IS) were compared in outpatients with bronchiectasis and chronic sputum expectoration. Participants inhaled each solution across four consecutive sessions. All sessions, except on session 3, also included 30 minutes of airway clearance technique. A 7-day washout period was applied. Sputum weight was collected during the sessions (primary outcome) as well as during a 24-hour follow-up. The Leicester Cough Questionnaire (LCQ) and lung function were measured before/after each treatment arm. Safety was assessed by the monitoring of adverse events (AEs). Results: Twenty-eight patients with bronchiectasis (mean age of 64.0 (17.9) and FEV1% 60.9 (24.6) of predicted) were recruited. HS and HA+HS promoted similar expectoration during sessions, both being greater than IS [median difference HS vs. IS 3.7 g (95% CI 0.5-6.9); HA+HS vs. IS 3.2 g (95%CI 0.5-5.9)]. Sputum expectorated exclusively during the ACT period was similar across all treatment arms [HS vs. IS −0.3 g (95% CI −1.7 to 0.9); HA+HS vs. IS 0.0 g (95% CI −1.3 to 1.4); HS vs. HA+HS 0.0 g (95% CI −1.2 to 0.4)]. Sputum collected over the 24-hour follow-up tended to be lower for HS and HA+HS compared with IS [HS vs. IS −1.7 g (95% CI −4.2 to 0.0); HA+HS vs. IS −1.1 g (95%CI −3.6 to 0.7)]. No differences in LCQ or lung function were observed. Most severe AEs were reported using HS. Conclusion: HS and HA+HS were more effective on sputum expectoration than IS in patients with bronchiectasis, reporting HA+HS better safety profile than HS

Health of Spanish centenarians: A cross-sectional study based on electronic health records

Background: With the number of centenarians increasing exponentially in Spain, a deeper knowledge of their socio-demographic, clinical, and healthcare use characteristics is important to better understand the health profile of the very elderly. Methods: We conducted a retrospective, cross-sectional observational study in the EpiChron Cohort (Aragon, Spain) aimed at analyzing the socio-demographic, clinical, drug use and healthcare use characteristics of 1680 centenarians during 2011-2015, using data from electronic health records and clinical-administrative databases. Results: Spanish centenarians (79.1% women) had 101.6 years on average. Approximately 80% of centenarians suffered from multimorbidity, with an average of 4.0 chronic conditions; 50% were exposed to polypharmacy, with an average of 4.8 medications; only 6% of centenarians were free of chronic diseases and only 7% were not on medication. Centenarians presented a cardio-cerebrovascular pattern in which hypertension, heart failure, cerebrovascular disease and dementia were the most frequent conditions. Primary care was the most frequently visited healthcare level (79% of them), followed by medical specialist consultations (23%), hospitalizations (13%), and emergency service use (9%). Conclusions: Multimorbidity is the rule rather than the exception in Spanish centenarians. Addressing medical care in the very elderly from a holistic geriatric view is critical in order to preserve their health, and avoid the negative effects of polypharmacy

Europium doped-double sodium bismuth molybdate nanoparticles as contrast agents for luminescence bioimaging and X-ray computed tomography

A one-pot method for the synthesis of uniform Eu3+-doped NaBi(MoO4)2 nanoparticles with an ellipsoidal shape and tetragonal crystal structure functionalized with polyacrylic acid is reported for the first time in the literature. The method is based on a homogeneous precipitation reaction from solutions in an ethylene glycol/water medium containing appropriate bismuth, sodium, and molybdate precursors and polyacrylic acid. The luminescence properties (excitation and emission spectra and luminescence lifetime) of such nanoparticles are evaluated for different Eu3+ doping levels, finding an intense red emission for all synthesized samples. The X-ray attenuation properties of the nanoparticles have been also analyzed, which were found to be better than those of a commercially computed tomography contrast agent (iohexol). The dispersibility of the nanoparticles in a physiological medium was also analyzed, finding that they could be well dispersed in a 2-N-morpholinoethanesulfonic acid monohydrate medium (pH = 6.5). Finally, the cell viability of such a phosphor has been analyzed using MIA-PaCa-2 cells and its in vivo toxicity has been evaluated using the nematode Caenorhabditis elegans model finding no significant toxicity in both cases up to a nanoparticle concentration of 100 μg mL−1, which is within the range required for most in vivo applications. The developed Eu3+-doped NaBi(MoO4)2 nanoparticles are, therefore, excellent candidates for their use as bimodal probes for luminescence imaging and X-ray computed tomography

Outcomes of patients with heart failure with preserved ejection fraction discharged on treatment with neurohormonal antagonists after an episode of decompensation

Aims: To analyze the frequency with which patients with heart failure with preserved ejection fraction (HFpEF) discharged after an acute heart failure (AHF) episode are treated with antineurohormonal drugs (ANHD), the variables related to ANHD prescription and their relationship with outcomes. Methods: We included consecutive HFpEF patients (left ventricular ejection fraction >= 50%) discharged after an AHF episode from 45 Spanish hospitals whose chronic medications and treatment at discharge were available. Patients were classified according to whether they were discharged with or without ANHD, including beta-blockers (BB), renin-angiotensin-aldosterone-system inhibitors (RAASi) and mineralcorticosteroid-receptor antagonists (MRA). Co-primary outcomes consisted of 1-year all-cause mortality and 90-day combined adverse event (revisit to emergency department -ED-, hospitalization due to AHF or all-cause death). Secondary outcomes were 90-day adverse events taken individually. Adjusted associations of ANHD treatment with outcomes were calculated. Results: We analyzed 3,305 patients with HFpEF (median age: 83, 60% women), 2,312 (70%) discharged with ANHD. The ANHD most frequently prescribed was BB (45.8%). The 1-year mortality was 26.9% (adjusted HR for ANHD patients:1.17, 95%CI=0.98-1.38) and the 90-day combined adverse event was 54.4% (HR=1.14, 95% CI=0.99-1.31). ED revisit was significantly increased by ANHD (HR=1.15, 95%CI=1.01-1.32). MRA and BB were associated with worse results in some co-primary or secondary endpoints, while RAASi (alone) reduced 90-day hospitalization (HR=0.73, 98%CI=0.56-0.96). Conclusion: 70% of HFpEF patients are discharged with ANHD after an AHF episode. ANHD do not seem to reduce mortality or adverse events in HFpEF patients, only RAASi could provide some benefits, reducing the risk of hospitalization for AHF

Maximal respiratory pressure reference equations in healthy adults and cut-off points for defining respiratory muscle weakness

[Abstract] Introduction: Maximal inspiratory and expiratory pressures (PImax/PEmax) reference equations obtained in healthy people are needed to correctly interpret respiratory muscle strength. Currently, no clear cut-off points defining respiratory muscle weakness are available. We aimed to establish sex-specific reference equations for PImax/PEmax in a large sample of healthy adults and to objectively determine cut-off points for respiratory muscle weakness. Methods: A multicentre cross-sectional study was conducted across 14 Spanish centres. Healthy non-smoking volunteers aged 18-80 years stratified by sex and age were recruited. PImax/PEmax were assessed using uniform methodology according to international standards. Multiple linear regressions were used to obtain reference equations. Cut-off points for respiratory muscle weakness were established by using T-scores. Results: The final sample consisted of 610 subjects (314 females; 48 [standard deviation, SD: 17] years). Reference equations for PImax/PEmax included body mass index and a squared term of the age as independent variables for both sexes (p<0.01). Cut-off points for respiratory muscle weakness based on T-scores ≥2.5 SD below the peak mean value achieved at a young age were: 62 and 83cmH2O for PImax and 81 and 109cmH2O for PEmax in females and males, respectively. Conclusion: These reference values, based on the largest dataset collected in a European population to date using uniform methodology, help identify cut-off points for respiratory muscle weakness in females and males. These data will help to better identify the presence of respiratory muscle weakness and to determine indications for interventions to improve respiratory muscle function

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continue

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica