Validation of smart nanoparticles as controlled drug delivery systems: loading and pH-dependent release of pilocarpine

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%-DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.Peer ReviewedPostprint (published version

Variational modularity at the cell level : insights from the sperm head of the house mouse

Background: Modularity is an important feature in the evolvability of organisms, since it allows the occurrence of complex adaptations at every single level of biological systems. While at the cellular level the modular organization of molecular interactions has been analyzed in detail, the phenotypic modularity (or variational modularity) of cell shape remains unexplored. The mammalian spermatozoon constitutes one of the most complex and specialized cell types found in organisms. The structural heterogeneity found in the sperm head suggests an association between its inner composition, shape and specificity of function. However, little is known about the extent of the connections between these features. Taking advantage of the house mouse sperm morphology, we analyzed the variational modularity of the sperm head by testing several hypotheses related to its structural and functional organization. Because chromosomal rearrangements can affect the genotype-phenotype map of individuals and thus modify the patterns of covariation between traits, we also evaluate the effect of Robertsonian translocations on the modularity pattern of the sperm head. Results: The results indicated that the house mouse sperm head is divided into three variational modules (the acrosomal, post-acrosomal and ventral spur module), which correspond to the main regions of the cytoskeletal mesh beneath the plasma membrane, i.e., the perinuclear theca. Most of the covariation is concentrated between the ventral spur and the acrosomal and post-acrosomal modules. Although the Rb fusions did not alter the main modularity pattern, they did affect the percentages of covariation between pairs of modules. Conclusions: The structural heterogeneity of the cytoskeleton is responsible for the modular organization of the sperm head shape, corroborating the role that this structure has in maintaining the cell shape. The reduction in percentages of shape covariation between pairs of modules in Rb sperms suggests that chromosomal rearrangements could induce changes in the genotype-phenotype map. Nevertheless, how these variations affect sperm fertilization success is yet to be elucidated

Nutritional Ergogenic Aids in Combat Sports: A Systematic Review and Meta-Analysis

Nutritional ergogenic aids (NEAs) are substances included within the group of sports supplements. Although they are widely consumed by athletes, evidence-based analysis is required to support training outcomes or competitive performance in specific disciplines. Combat sports have a predominant use of anaerobic metabolism as a source of energy, reaching peak exertion or sustained effort for very short periods of time. In this context, the use of certain NEAs could help athletes to improve their performance in those specific combat skills (i.e., the number of attacks, throws and hits; jump height; and grip strength, among others) as well as in general physical aspects (time to exhaustion [TTE], power, fatigue perception, heart rate, use of anaerobic metabolism, etc.). Medline/PubMed, Scopus and EBSCO were searched from their inception to May 2022 for randomised controlled trials (RCTs). Out of 677 articles found, 55 met the predefined inclusion criteria. Among all the studied NEAs, caffeine (5–10 mg/kg) showed strong evidence for its use in combat sports to enhance the use of glycolytic pathways for energy production during high-intensity actions due to a greater production of and tolerance to blood lactate levels. In this regard, abilities including the number of attacks, reaction time, handgrip strength, power and TTE, among others, were improved. Buffering supplements such as sodium bicarbonate, sodium citrate and beta-alanine may have a promising role in high and intermittent exertion during combat, but more studies are needed in grappling combat sports to confirm their efficacy during sustained isometric exertion. Other NEAs, including creatine, beetroot juice or glycerol, need further investigation to strengthen the evidence for performance enhancement in combat sports. Caffeine is the only NEA that has shown strong evidence for performance enhancement in combat sports

Exciton Gas Compression and Metallic Condensation in a Single Semiconductor Quantum Wire

We study the metal-insulator transition in individual self-assembled quantum wires and report optical evidences of metallic liquid condensation at low temperatures. Firstly, we observe that the temperature and power dependence of the single nanowire photoluminescence follow the evolution expected for an electron-hole liquid in one dimension. Secondly, we find novel spectral features that suggest that in this situation the expanding liquid condensate compresses the exciton gas in real space. Finally, we estimate the critical density and critical temperature of the phase transition diagram at $n_c\sim1\times10^5$ cm$^{-1}$ and $T_c\sim35$ K, respectively.Comment: 4 pages, 5 figure

Effect of chromosomal reorganizations on morphological covariation of the house mouse mandible: insights from a Robertsonian system of Mus musculus domesticus

Morphological integration and modularity depend on genetic covariation between traits, which emerges from pleiotropic effects of single loci and genetic linkage between loci. Since chromosomal reorganizations alter meiotic recombination, they might modify groups of linked genes and entail the fixation of new alleles with new pleiotropic effects. As a result, they could contribute to the intraspecific variation of the covariance structure of morphological traits. Although the mouse mandible has long been studied in terms of development and evolution, little is known about how its covariance structure varies in natural populations with chromosomal reorganizations. Consequently, here we analyzed the magnitude and patterns of morphological covariation of mandible shape in groups of mice with different karyotypes from a Robertsonian system of Mus musculus domesticus. Results: The organization of the mouse mandible into two main modules was confirmed in all chromosomal groups, since RV coefficients for the corresponding subdivision of landmarks were always significant. However, substantial variation in the magnitude of integration was detected between groups, especially when the effect of allometry was not removed. A significant positive correlation between differences in magnitude of integration of the symmetric component of shape and karyotypic distances between groups was detected when not correcting for size. Moreover, the degree of dependence of symmetric shape variation on size showed a negative association with the chromosome number and a positive association with the magnitude of integration. All groups showed similar patterns of morphological integration of the mandible, especially regarding the symmetric component of shape. However, the display of landmark displacements and the computation of vector angles highlighted some differences. In addition, distances between groups in terms of covariation matrices of the symmetric component were positively correlated with geographic distance. Conclusions: Robertsonian translocations do not alter the organization of the mouse mandible into two main modules, but do affect the magnitude of integration between them. This effect is mainly due to changes in the allometric relationship. In the 'Barcelona' Robertsonian system, geographically structured sources of variation seem to affect the patterns of integration by producing parallel variation in separate developmental pathways. Overall, our results suggest that Robertsonian translocations could play a role in intraspecific differentiation processes by producing changes in the covariance structure of morphological traits

Hepatitis C infection substantially reduces survival of alcohol-dependent patients

Background: Heavy alcohol use is associated with life-threatening complications including progressive liver disease. We aimed to analyze the impact of hepatitis C virus (HCV) infection on survival and liver-related death in alcohol-dependent patients. Patients and methods: This is a longitudinal study in patients seeking treatment of alcohol abuse between 2000 and 2010. Information on alcohol use characteristics, alcoholic liver disease, and HCV infection were obtained at entry. Cumulated mortality and causes of death were ascertained through clinical records and death registry. Results: A total of 819 patients (81.6% men) underwent ethanol detoxification; age was 44 (interquartile range [IQR] 38-51) years; the duration of heavy alcohol use was 14 (IQR 6-24) years; and the alcohol consumption was 190 (IQR 120-250) g/day. The prevalence of HCV infection was 15.8%. There were 129 (16.9%) deaths during 5,117 persons-year (p-y) of follow-up (median follow-up 6.4 [IQR 4.3-9.2] years); 31 (24.6%) deaths were observed among the HCV-positive patients, and 98 (15.4%) deaths were observed among the HCV-negative patients. The mortality rate was significantly (P=0.03) higher among the HCV-positive patients (3.84x100 p-y; 95% confidence interval [CI]: 2.70, 5.46) than among the HCV-negative patients (2.27x100 p-y; 95% CI: 1.86, 2.77). Survival times for the HCV infected patients were 34% shorter (time ratio relative to HCV negative: 0.66; 95% CI: 0.51,0.86). The main causes of death in the HCV-positive and -negative patients were liver-related mortality (48.4%) and neoplasia (22.4%), respectively. The liver-related mortality was significantly higher among the HCV-positive patients (adjusted sub-distribution hazard ratio [asHR] 3.65; 95% CI: 1.72, 7.78; P=0.001). Conclusion: HCV infection compromises the survival of patients with alcohol abuse/dependence. The new direct antiviral agents for the treatment of HCV infection may result in better clinical outcomes

Charge control in laterally coupled double quantum dots

We investigate the electronic and optical properties of InAs double quantum dots grown on GaAs (001) and laterally aligned along the [110] crystal direction. The emission spectrum has been investigated as a function of a lateral electric field applied along the quantum dot pair mutual axis. The number of confined electrons can be controlled with the external bias leading to sharp energy shifts which we use to identify the emission from neutral and charged exciton complexes. Quantum tunnelling of these electrons is proposed to explain the reversed ordering of the trion emission lines as compared to that of excitons in our system.Comment: 4 pages, 4 figures submitted to PRB Rapid Com

Effects of pomegranate juice in circulating parameters, cytokines, and oxidative stress markers in endurance-based athletes: A randomized controlled trial

Objective: The aim of the present study was to assess the effects of pomegranate juice on the level of oxidative stress in the blood of endurance-based athletes. Pomegranate juice is rich in polyphenols, conferring it a higher antioxidant capacity than other beverages with polyphenolic antioxidants. Methods: A randomized double-blind, multicenter trial was performed in athletes from three different sport clubs located in southeastern of Spain. Plasma oxidative stress markers (protein carbonyls and malondialdehyde [MDA]) as well as C-reactive protein and sE-selectin were measured. Thirty-one athletes participated in the study. Participants were divided into three groups. The first group was supplemented with 200 mL/d pomegranate juice (PJ; n = 10) over a 21-d period, the second with 200 mL/d pomegranate juice diluted 1:1 with water (PJD; n = 11), and a control group that did not consume pomegranate juice (C; n = 10). Nine athletes were excluded due to protocol violations (n = 4 in the PJ group and n = 5 in the PJD group) because they did not observe the 24 h of rest before the last blood test. Results: The control group increased levels of carbonyls (+0.7 ± 0.3 nmols/mg protein) and MDA (+3.2 ± 1.0 nmols/g protein), whereas the PJ and PJD groups maintained or decreased their levels, respectively. On the other hand, lactate levels increased in the PJ group (from 10.3 at day 0 to 21.2 mg/dL at day 22). A nonsignificant decrease was detected in sE-selectin and C-reactive protein in the groups consuming pomegranate juice. Conclusion: Consumption of pomegranate juice over a 21-d period improved MDA levels and carbonyls, and thus decreased the oxidative damage caused by exercise.This research received specific grant and provision of supplements from Vitalgrana SL. The following institutions are acknowledged PROMETEO/2012/007 from Generalitat Valenciana and CIBEROBN (Fisiopatología de la Obesidad y la Nutrición CB12/03/30038) Instituto de Salud Carlos III, Spain to E Roche

Validation of a Spanish version of the Leicester Cough Questionnaire in cystic fibrosis

Bronchiectasis; Quality of life; Respiratory diseaseBronquiectasia; Calidad de vida; Enfermedad respiratoriaBronquiectàsia; Qualitat de vida; Malaltia respiratòriaCough is a main symptom in cystic fibrosis (CF). We aim to validate a Spanish version of the Leicester Cough Questionnaire (LCQ-Sp) to measure the impact of cough in CF bronchiectasis. A prospective longitudinal multicentre study was performed. Internal consistency and score changes over a 15-day period in stable state were assessed to analyse reliability. Concurrent validity was analysed by correlation with Saint George’s Respiratory Questionnaire (SGRQ) and convergent validity by assessing the association with clinical variables. Changes in scores between stable state and the first exacerbation were assessed to analyse responsiveness. 132 patients (29.73 ± 10.52 years) were enrolled in four hospitals. Internal consistency was high for the total score and good for the three domains (Cronbach’s α 0.81–0.93). The test–retest reliability showed an intraclass correlation coefficient of 0.86 for the total score. The correlation between LCQ-Sp and SGRQ scores was −0.74. The LCQ-Sp score negatively correlated with sputum volume, and the mean score decreased at the beginning of exacerbations (16.04±3.81 vs 13.91±4.29) with a large effect size. The LCQ-Sp is a reliable, repeatable and responsive instrument to assess the impact of cough in CF bronchiectasis and is responsive to change in the event of exacerbations.The author(s) received no financial support for the research, authorship, and/or publication of this article