Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

Self-assembling proteins are gaining attention as building blocks for application-tailored nanoscale materials. This is mostly due to the biocompatibility, biodegradability, and functional versatility of peptide chains. Such a potential for adaptability is particularly high in the case of recombinant proteins, which are produced in living cells and are suitable for genetic engineering. However, how the cell factory itself and the particular protein folding machinery influence the architecture and function of the final material is still poorly explored. In this study we have used diverse analytical approaches, including small-angle X-ray scattering (SAXS) and field emission scanning electron microscopy (FESEM) to determine the fine architecture and geometry of recombinant, tumor-targeted protein nanoparticles of interest as drug carriers, constructed on a GFP-based modular scheme. A set of related oligomers were produced in alternative Escherichia coli strains with variant protein folding networks. This resulted in highly regular populations of morphometric types, ranging from 2.4 to 28 nm and from spherical- to rod-shaped materials. These differential geometric species, whose relative proportions were determined by the features of the producing strain, were found associated with particular fluorescence emission, cell penetrability and receptor specificity profiles. Then, nanoparticles with optimal properties could be analytically identified and further isolated from producing cells for use. The cell’s protein folding machinery greatly modulates the final geometry reached by the constructs, which in turn defines the key parameters and biological performance of the material.Peer ReviewedPostprint (author's final draft

Efectividad de la analgesia antisipatoria con antiinflamatorios no esteroideos en la operación traumatológica de urgencia

One hundred and twenty ASA grade I and II patients were prospectively studied. They were randomly assigned in groups of 40: those who received orally, one hour prior to the operation, naproxen (250 mg); those who received ibuprofen (400 mg) and those who received placebo. All of them received general endotracheal anesthesia. The behavior of the respiratory rate, heart rate and systolic and diastolic blood pressures were analyzed at six, 12, 18 and 24 hours after surgery in relation to baseline levels.  The postoperative analgesic quality was assessed according to the visual analogue scale in the aforementioned periods. The incidence of side effects was registered and the analgesia was supplemented with tramadol hydrochloride. Male sex and age group between 36 and 50 years proved to show the highest incidence in the sample. The groups I and II showed better hemodynamic stability with respect to the placebo group. The quality of analgesia was superior in the naproxen group followed by the ibuprofen group. The most frequent side effects were nausea, epigastric pain and headache. It can be said that oral premedication with naproxen and ibuprofen was effective in controlling postoperative pain, with good hemodynamic stability and low incidence of side effects related to their use.Se estudiaron prospectivamente 120 pacientes grado I y II (según la clasificación de la Sociedad Norteamericana de Anestesiología) asignados aleatoriamente en grupos de 40, los que recibieron, una hora previa a la operación, naproxeno (250 mg), ibuprofeno (400 mg) y placebo, vía oral; todos recibieron anestesia general endotraqueal. Fue analizado el comportamiento de la frecuencia respiratoria, de la frecuencia cardiaca y de las tensiones arteriales sistólica y diastólica a las 6, 12, 18 y 24 horas del postoperatorio en relación con las cifras basales; se evaluó la calidad analgésica postoperatoria según la escala analógica visual en los períodos antes mencionados; se recogió la incidencia de efectos colaterales y se suplementó la analgesia con clorhidrato de tramadol. El sexo masculino y el grupo etario entre 36-50 años resultaron ser los de mayor incidencia en la muestra estudiada; los grupos I y II mostraron mejor estabilidad hemodinámica en relación al grupo placebo; la calidad de la analgesia resultó ser superior en el grupo naproxeno, seguida del grupo ibuprofeno; los efectos colaterales más frecuentes fueron las náuseas, la epigastralgia y la cefalea. La premedicación oral con naproxeno e ibuprofeno resultó ser efectiva en el control del dolor agudo postoperatorio, con buena estabilidad hemodinámica y con baja incidencia de efectos colaterales en relación con su uso

Genetic Admixture and Population Substructure in Guanacaste Costa Rica

The population of Costa Rica (CR) represents an admixture of major continental populations. An investigation of the CR population structure would provide an important foundation for mapping genetic variants underlying common diseases and traits. We conducted an analysis of 1,301 women from the Guanacaste region of CR using 27,904 single nucleotide polymorphisms (SNPs) genotyped on a custom Illumina InfiniumII iSelect chip. The program STRUCTURE was used to compare the CR Guanacaste sample with four continental reference samples, including HapMap Europeans (CEU), East Asians (JPT+CHB), West African Yoruba (YRI), as well as Native Americans (NA) from the Illumina iControl database. Our results show that the CR Guanacaste sample comprises a three-way admixture estimated to be 43% European, 38% Native American and 15% West African. An estimated 4% residual Asian ancestry may be within the error range. Results from principal components analysis reveal a correlation between genetic and geographic distance. The magnitude of linkage disequilibrium (LD) measured by the number of tagging SNPs required to cover the same region in the genome in the CR Guanacaste sample appeared to be weaker than that observed in CEU, JPT+CHB and NA reference samples but stronger than that of the HapMap YRI sample. Based on the clustering pattern observed in both STRUCTURE and principal components analysis, two subpopulations were identified that differ by approximately 20% in LD block size averaged over all LD blocks identified by Haploview. We also show in a simulated association study conducted within the two subpopulations, that the failure to account for population stratification (PS) could lead to a noticeable inflation in the false positive rate. However, we further demonstrate that existing PS adjustment approaches can reduce the inflation to an acceptable level for gene discovery

Validation of the Walking Behavior Questionnaire (WBQ): A tool for measuring risky and safe walking under a behavioral perspective

Introduction: Although daily walking implies several potential benefits for the health and wellbeing of people, and, besides the raise of more 'walkable' cities, it is currently being promoted as an active transportation means that is rich in benefits for its users, road risks affecting pedestrians, together with their high vulnerability to suffer severe injuries as a consequence of traffic crashes, have turned into a relevant concern for both policymakers and public health practitioners. In this regard, risky and positive (proactively safe) behaviors have acquired a substantial relevance for the study and prevention of traffic causalities involving different road users, including pedestrians. Objective: The objective of this study was to thoroughly describe the validation of an instrument for measuring the walking risky and positive behavior on the road, using the Walking Behavior Questionnaire (WBQ). Methods: This cross-sectional study analyzed the data from 1070 Spanish pedestrians answering a questionnaire on road behaviors. The data were analyzed using the competitive Confirmatory Factor Analysis (CFA), thus obtaining basic psychometric properties, testing convergent validity and predictive value, and presenting an optimized structure for the scale. Results: The obtained findings suggest that the WBQ has a clear dimensional structure, items with high factorial weight, good internal consistency and reliability and an adequate convergent validity with variables theoretically associated with road behaviors. Conclusion: The results of this study endorse the psychometric value of the WBQ for measuring errors, violations and positive behaviors of pedestrians. This questionnaire might have relevant applications in the practical field, since, apart from having good psychometric properties, it introduces items related to social and technological trends (e.g., the use of cellphones) that may compromise pedestrians' safety. This can be particularly useful for designing behavioral-based interventions and educational programs, focused on road risk reduction and on the promotion of safe walking behavior

HbA1c levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions

Aims/hypothesis: We evaluated seasonal HbA$_{1c}$ changes in children with type 1 diabetes and its relation with measures of weather conditions. Methods: HbA$_{1c}$ changes over more than 3 years were evaluated in type 1 diabetic patients who were younger than 18 years and had diabetes duration of more than 12 months, and correlated with measures of weather conditions (ambient temperature, hours of sunshine and solar irradiance). After comparison of autocorrelation patterns, patterns of metabolic control and meteorological data were evaluated using Spearman rank correlation. Results: A total of 3,935 HbA$_{1c}$ measurements in 589 school (≥7 years) and 88 preschool (<7 years) children were analysed. Mean (±SD) HbA$_{1c}$ level for the whole study period was 7.65±1.12%. The lowest HbA$_{1c}$ levels were observed in late summer and the highest in winter months, with differences consistently exceeding 0.44%. Autocorrelation analysis of HbA$_{1c}$ levels in schoolchildren showed a sine-wave pattern with a cycle length of roughly 12 months, which mirrored changes in ambient temperature. Strong negative correlations of HbA$_{1c}$ with ambient temperature (R=−0.56; p=0.0002), hours of sunshine (R=−0.52; p=0.0007) and solar irradiance (R=−0.52; p=0.0006) were present in schoolchildren, but not in preschoolers (p≥0.29 for each correlation). Conclusions/interpretation: Seasonal changes of HbA$_{1c}$ levels in schoolchildren with type 1 diabetes are a significant phenomenon and should be considered in patient education and diabetes management. They may potentially affect the results of clinical trials using HbA$_{1c}$ levels as their primary outcome, as well as HbA$_{1c}$-based diagnosis of diabetes

Cryptic Speciation in Brazilian Epiperipatus (Onychophora: Peripatidae) Reveals an Underestimated Diversity among the Peripatid Velvet Worms

Taxonomical studies of the neotropical Peripatidae (Onychophora, velvet worms) have proven difficult, due to intraspecific variation and uniformity of morphological characters across this onychophoran subgroup. We therefore used molecular approaches, in addition to morphological methods, to explore the diversity of Epiperipatus from the Minas Gerais State of Brazil.Our analyses revealed three new species. While Epiperipatus diadenoproctussp. nov. can be distinguished from E. adenocryptussp. nov. and E. paurognostussp. nov. based on morphology and specific nucleotide positions in the mitochondrial cytochrome c oxidase subunit I (COI) and small ribosomal subunit RNA gene sequences (12S rRNA), anatomical differences between the two latter species are not evident. However, our phylogenetic analyses of molecular data suggest that they are cryptic species, with high Bayesian posterior probabilities and bootstrap and Bremer support values for each species clade. The sister group relationship of E. adenocryptussp. nov. and E. paurognostussp. nov. in our analyses correlates with the remarkable morphological similarity of these two species. To assess the species status of the new species, we performed a statistical parsimony network analysis based on 582 base pairs of the COI gene in our specimens, with the connection probability set to 95%. Our findings revealed no connections between groups of haplotypes, which have been recognized as allopatric lineages in our phylogenetic analyses, thus supporting our suggestion that they are separate species.Our findings suggest high cryptic species diversity and endemism among the neotropical Peripatidae and demonstrate that the combination of morphological and molecular approaches is helpful for clarifying the taxonomy and species diversity of this apparently large and diverse onychophoran group

The number of tree species on Earth

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global ground sourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are ∼73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness. Please note an (erratum/corrigendum) for this article is available via https://www.pnas.org/doi/10.1073/pnas.220278411

Passive smoking in babies: The BIBE study (Brief Intervention in babies. Effectiveness)

Background: There is evidence that exposure to passive smoking in general, and in babies in particular, is an important cause of morbimortality. Passive smoking is related to an increased risk of pediatric diseases such as sudden death syndrome, acute respiratory diseases, worsening of asthma, acute-chronic middle ear disease and slowing of lung growth. The objective of this article is to describe the BIBE study protocol. The BIBE study aims to determine the effectiveness of a brief intervention within the context of Primary Care, directed to mothers and fathers that smoke, in order to reduce the exposure of babies to passive smoking (ETS). Methods/Design: Cluster randomized field trial (control and intervention group), multicentric and open. Subject: Fathers and/or mothers who are smokers and their babies (under 18 months) that attend pediatric services in Primary Care in Catalonia. The measurements will be taken at three points in time, in each of the fathers and/or mothers who respond to a questionnaire regarding their baby's clinical background and characteristics of the baby's exposure, together with variables related to the parents' tobacco consumption. A hair sample of the baby will be taken at the beginning of the study and at six months after the initial visit (biological determination of nicotine). The intervention group will apply a brief intervention in passive smoking after specific training and the control group will apply the habitual care. Discussion: Exposure to ETS is an avoidable factor related to infant morbimortality. Interventions to reduce exposure to ETS in babies are potentially beneficial for their health. The BIBE study evaluates an intervention to reduce exposure to ETS that takes advantage of pediatric visits. Interventions in the form of advice, conducted by pediatric professionals, are an excellent opportunity for prevention and protection of infants against the harmful effects of ETS