Harmonized tuning of nucleic acid and lectin binding properties with multivalent cyclodextrins for macrophage-selective gene delivery

Polycationic amphiphilic cyclodextrins (paCDs) have been shown to behave as efficient non-viral gene carriers paralleling the efficacy of commercial vectors towards a variety of cell lines. Their molecular framework and modular design allow the installation of saccharidic antennae to promote specific carbohydrate–protein interactions, thus potentially endowing them with selective targeting abilities. Yet, the presence of these additional functionalities onto the polycationic cluster may hamper paCD self-assembly and nucleic acid condensation. In this report we describe the influence of paCD mannosylation extent on paCD-pDNA nanocomplex stability as well as the consequences of varying glycotope density on mannose-specific lectin recognition and gene delivery capabilities. The work aims at exploring the potential of this approach to optimize both properties in order to modulate cell transfection selectivity.Ministerio de Economía y Competitividad SAF2013-44021-RJunta de Andalucía FQM-146

Estudio sobre la automedicación en una localidad de bogotá

Objetivos Establecer la prevalencia y condicionantes asociados al uso de medicamentos por cuenta propia por parte de los habitantes de Suba en Bogotá.Métodos Aplicación de una encuesta pilotada a una muestra aleatoria.  Se midieron variables demográficas y se indagó por problemas de salud relacionados con la automedicación, motivos para no consultar al médico y medicamentos consumidos durante las dos últimas semanasResultados La automedicación fue de 27,3 % (IC 95 %, 19,2 % - 35,3 %) y la autoprescripción de 7,7 % (IC 95%, 2,8 %-12,5 %). La afiliación al Sistema de beneficiarios de la Seguridad Social en Salud (OR=2,61  IC 95 % 1,4-4,8) está asociado con ésta conducta. No se encontró asociación con otras variables. Los medicamentos más consumidos por automedicación son analgésicos (59,3 %), antigripales (13,5 %) y vitaminas (6,8 %).  Los principales problemas por los cuales las personas se automedican son dolor, fiebre y gripa.  Las principales razones que se mencionan para no asistir al médico son falta de tiempo (40 %) y recursos económicos (43 %), además de otros argumentos como la percepción de que el problema es leve y la congestión en los servicios de urgencia.Conclusiones Las cifras de automedicación aunque todavía preocupantes desde el punto de vista de salud pública, son más bajas que las encontradas en estudios similares; los medicamentos consumidos por automedicación pertenecen a la categoría de venta libre y el consumo de antibióticos por automedicación bajó, posiblemente debido a la intensa difusión que se dio a la restricción de venta de antibióticos sin fórmula médica, unos meses antes de la realización de la encuesta

Exomer Is Part of a Hub Where Polarized Secretion and Ionic Stress Connect

[EN] Plasma membrane and membranous organelles contribute to the physiology of the Eukaryotic cell by participating in vesicle trafficking and the maintenance of ion homeostasis. Exomer is a protein complex that facilitates vesicle transport from the trans-Golgi network to the plasma membrane, and its absence leads to the retention of a set of selected cargoes in this organelle. However, this retention does not explain all phenotypes observed in exomer mutants. The Schizosaccharomyces pombe exomer is composed of Cfr1 and Bch1, and cfr1¿ and bch1¿ were sensitive to high concentrations of potassium salts but not sorbitol, which showed sensitivity to ionic but not osmotic stress. Additionally, the activity of the plasma membrane ATPase was higher in exomer mutants than in the wild-type, pointing to membrane hyperpolarization, which caused an increase in intracellular K+ content and mild sensitivity to Na+, Ca2+, and the aminoglycoside antibiotic hygromycin B. Moreover, in response to K+ shock, the intracellular Ca2+ level of cfr1¿ cells increased significantly more than in the wild-type, likely due to the larger Ca2+ spikes in the mutant. Microscopy analyses showed a defective endosomal morphology in the mutants. This was accompanied by an increase in the intracellular pools of the K+ exporting P-type ATPase Cta3 and the plasma membrane Transient Receptor Potential (TRP)-like Ca2+ channel Pkd2, which were partially diverted from the trans-Golgi network to the prevacuolar endosome. Despite this, most Cta3 and Pkd2 were delivered to the plasma membrane at the cell growing sites, showing that their transport from the trans-Golgi network to the cell surface occurred in the absence of exomer. Nevertheless, shortly after gene expression in the presence of KCl, the polarized distribution of Cta3 and Pkd2 in the plasma membrane was disturbed in the mutants. Finally, the use of fluorescent probes suggested that the distribution and dynamics of association of some lipids to the plasma membrane in the presence of KCl were altered in the mutants. Thus, exomer participation in the response to K+ stress was multifaceted. These results supported the notion that exomer plays a general role in protein sorting at the trans-Golgi network and in polarized secretion, which is not always related to a function as a selective cargo adaptor.Financial support from the Spanish Ministerio de Economía, Industria y Competitividad/European Regional Development Fund¿FEDER¿program (BFU2017-84508-P to M-HV and PGC2018-098924-B-I00 to PP), and from the Junta de Castilla y Leon/FEDER program (CSI150P20 to PP, and ¿Escalera de Excelencia¿ CLU-2017-03/14-20 to the IBFG), made this work possible. SM was supported by fellowships from the Universidad de Salamanca and the Spanish Ministerio de Educación, and EMR by a fellowship from Junta de Castilla y León. The Agencia Española de Investigación (AEI) Grants PID2019-104054 GB-I00 and RTC-2017-6468-2-AR supported JM. QC and AP were supported by the University of Toledo start up fund and a grant from National Institutes of Health (R15GM134496).Moro, S.; Moscoso-Romero, E.; Poddar, A.; Mulet, JM.; Pérez, P.; Chen, Q.; Valdivieso, M. (2021). Exomer Is Part of a Hub Where Polarized Secretion and Ionic Stress Connect. Frontiers in Microbiology. 12:1-22. https://doi.org/10.3389/fmicb.2021.708354S1221

MOF-Based Materials with Sensing Potential: Pyrrolidine-Fused Chlorin at UiO-66(Hf) for Enhanced NO2 Detection

An efficient strategy to develop porous materials with potential for NO2 sensing was based in the preparation of a metal-organic framework (MOF), UiO-66(Hf), modified with a very small amount of meso-tetrakis(4-carboxyphenyl) N-methylpyrrolidine-fused chlorin (TCPC), TCPC@MOF. Chlorin’s incorporation into the UiO-66(Hf) framework was verified by several characterization methods and revealed that the as-synthesized TCPC@MOF brings together the chemical stability of UiO-66(Hf) and the photophysical properties of the pyrrolidine-fused chlorin which is about five times more emissive than the porphyrin counterpart. TCPC@MOF was further incorporated into polydimethylsiloxane (PDMS) and the resulting TCPC@MOF@PDMS film was tested in NO2 gas sensing. It showed notable sensitivity as well as a fast response in the range between 0.5 and 500 ppm where an emission intensity quenching is observed up to 96% for 500 ppm. This is a rare example of a chlorin-derivative used for gas-sensing applications through emission changes, and an unusual case of this type of optical-sensing composites of NO2.FCT-MCTE

Composition law of cardinal order permutations

In this paper the theorems that determine composition laws for both cardinal ordering permutations and their inverses are proven. So, the relative positions of points in a hs-periodic orbit become completely known as well as in which order those points are visited. No matter how a hs-periodic orbit emerges, be it through a period doubling cascade (s=2^n) of the h-periodic orbit, or as a primary window (like the saddle-node bifurcation cascade with h=2^n), or as a secondary window (the birth of a $s-$periodic window inside the h-periodic one). Certainly, period doubling cascade orbits are particular cases with h=2 and s=2^n. Both composition laws are also shown in algorithmic way for their easy use

Prevalence of periodontal disease in patients with a history of acute coronary syndrome in a cardiac rehabilitation programme

Objetivo establecer la prevalencia y la gravedad de la enfermedad periodontal en pacientes con síndrome coronario agudo sin comorbilidades, que ingresan al programa de rehabilitación cardíaca en la Fundación Clínica Shaio. Métodos se examinaron 83 pacientes con diagnóstico de síndrome coronario agudo sin comorbilidades y los siguientes diagnósticos: angina inestable (n = 27), infarto de miocardio con elevación del segmento ST (STEMI) (n = 34) e infarto de miocardio sin elevación del segmento ST (NSTEMI) (n = 22). La prevalencia y la gravedad de la enfermedad periodontal fueron evaluadas con el índice periodontal de los Centros para el Control y la Prevención de Enfermedades (CDC). Se compararon entre los grupos índice clínico, placa, cálculo, hemorragia gingival, profundidad de sondaje y nivel de inserción clínica. Resultados la prevalencia de enfermedad periodontal fue del 97,6% y se observó periodontitis avanzada en el 38,3%. Los pacientes con STEMI mostraron la mayor gravedad de la periodontitis. Los índices clínicos inflamatorios de la enfermedad periodontal se elevaron en todos los grupos sin diferencias significativas. El nivel de inserción clínica no mostró diferencias significativas entre las condiciones cardíacas. Sin embargo, se observó mayor porcentaje de sitios con pérdida de inserción clínica (PIC) ≥ 6mm, y sitios con una profundidad de bolsas> 6mm, en pacientes con STEMI. Conclusión los pacientes con síndrome coronario agudo sin comorbilidades, que ingresaron al programa de rehabilitación cardíaca para completar su tratamiento, tuvieron alta prevalencia y gravedad de la enfermedad periodontal. Es necesario hacer énfasis en el control de la enfermedad periodontal en pacientes con enfermedad coronaria.Objective To determine the prevalence and severity of periodontal disease in patients with acute coronary syndrome with no comorbidities admitted to a cardiac rehabilitation programme in the Clínica Shaio Foundation, Colombia. Methods The study included a total of 83 patients diagnosed with acute coronary syndrome with no comorbidities and the following diagnoses: unstable angina (n = 27), ST-segment elevation myocardial infarction (STEMI) (n = 34), and non-ST-elevation myocardial infarction (NSTEMI) (n = 22). The prevalence and severity of periodontal disease were evaluated using the Periodontal Index of the Centres for the Control and Prevention of Diseases. A between-group comparison was made of the clinical index, plaque, calculi, gingival bleeding, probing depth, and level of clinical attachment. Results The prevalence of periodontal disease was 97.6%, and advance periodontitis was observed in 38.3% of subjects. The patients with a STEMI showed more severe periodontitis. The inflammatory clinical indices of periodontal disease were increased in all groups, with no significant differences being observed. There were no significant differences between clinical attachment and heart conditions. However, it was observed that there was a higher percentage of locations with a loss of clinical attachment ≥ 6mm, and locations with bag depths> 6mm in patients with a STEMI. Conclusion The patients with acute coronary syndrome with no comorbidities, and who entered the cardiac rehabilitation programme to complete their treatment, had a high prevalence and severity of periodontal disease. The control of periodontal disease should be emphasised in patients with coronary disease

Prophage Spontaneous Activation Promotes DNA Release Enhancing Biofilm Formation in Streptococcus pneumoniae

Streptococcus pneumoniae (pneumococcus) is able to form biofilms in vivo and previous studies propose that pneumococcal biofilms play a relevant role both in colonization and infection. Additionally, pneumococci recovered from human infections are characterized by a high prevalence of lysogenic bacteriophages (phages) residing quiescently in their host chromosome. We investigated a possible link between lysogeny and biofilm formation. Considering that extracellular DNA (eDNA) is a key factor in the biofilm matrix, we reasoned that prophage spontaneous activation with the consequent bacterial host lysis could provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that phage-infected bacteria are more proficient at forming biofilms, that is their biofilms are characterized by a higher biomass and cell viability. The presence of phage particles throughout the lysogenic strains biofilm development implicated prophage spontaneous induction in this effect. Analysis of lysogens deficient for phage lysin and the bacterial major autolysin revealed that the absence of either lytic activity impaired biofilm development and the addition of DNA restored the ability of mutant strains to form robust biofilms. These findings establish that limited phage-mediated host lysis of a fraction of the bacterial population, due to spontaneous phage induction, constitutes an important source of eDNA for the S. pneumoniae biofilm matrix and that this localized release of eDNA favors biofilm formation by the remaining bacterial population

Au@p4VP core@shell pH-sensitive nanocomposites suitable for drug entrapment

11 p.-2 schem.-1 graph. abst.We synthesize and characterize pH-responsive hybrid nanocomposites with SERS and drug loading applications. This colloidal system is structured by spherical 50 nm Au cores individually coated by a pH-sensitive shell of poly4-vinylpyridine (Au@p4VP). The synthesis of these hybrid nanocomposites is performed in two steps, a first one involves the fabrication of vinyl-functionalized Au nanoparticles, and a second one includes the controlled overgrowth of a p4VP shell by free radical polymerization. As a result, Au@p4VP hybrid systems with a mean diameter ranging from 150 to 57 nm are obtained upon varying the monomer concentration at synthesis. Au@p4VP nanocomposite exhibits pH-response capabilities, confirmed by cryo-TEM analysis, Small Angle X-ray Scattering (SAXS) and Zeta Potential (ZP) measurements at different pH conditions. The Au@p4VP particles also display a controllable swelling response, which depends on the cross-linker density within the polymer. This swelling capability is analyzed by Dynamic Light Scattering (DLS), and UV–vis spectroscopy at different pHs. The pH-responsive capability is here exploited for the chemical entrapment of doxorubicin hydrochloride (Dox) into the polymer network. The presence of this molecule is resolved by Surface Enhanced Raman Spectroscopy (SERS) measurements. The entrapment efficiency of Dox by the Au@p4VP system is determined via NMR spectroscopy of the supernatants.JCR acknowledges funding from UOC, internal grant N116139473, aimed at enhancing submission to H2020 calls. RCC, JLR and JRR acknowledge financial support from the Spanish MINECO projects CTQ2013-48418P, CTQ2016-76311-R, BFU2016-75319-R and MAT2014-55065R. IF, RCC and ABRM thank the financial support given by Junta de Andalucía (Spain) under the project number P12-FQM-2668. J.F.D acknowledges the networking contributions by the COST actions CM1407 and CM1470.Peer reviewe

Implementation tells us more beyond pooled estimates: Secondary analysis of a multicountry mhealth trial to reduce blood pressure

Background: The uptake of an intervention aimed at improving health-related lifestyles may be influenced by the participant’s stage of readiness to change behaviors. Objective: We conducted secondary analysis of the Grupo de Investigación en Salud Móvil en América Latina (GISMAL) trial according to levels of uptake of intervention (dose-response) to explore outcomes by country, in order to verify the consistency of the trial’s pooled results, and by each participant’s stage of readiness to change a given lifestyle at baseline. The rationale for this secondary analysis is motivated by the original design of the GISMAL study that was independently powered for the primary outcome—blood pressure—for each country. Methods: We conducted a secondary analysis of a mobile health (mHealth) multicountry trial conducted in Argentina, Guatemala, and Peru. The intervention consisted of monthly motivational phone calls by a trained nutritionist and weekly tailored text messages (short message service), over a 12-month period, aimed to enact change on 4 health-related behaviors: salt added to foods when cooking, consumption of high-fat and high-sugar foods, consumption of fruits or vegetables, and practice of physical activity. Results were stratified by country and by participants’ stage of readiness to change (precontemplation or contemplation; preparation or action; or maintenance) at baseline. Exposure (intervention uptake) was the level of intervention (<50%, 50%-74%, and ≥75%) received by the participant in terms of phone calls. Linear regressions were performed to model the outcomes of interest, presented as standardized mean values of the following: blood pressure, body weight, body mass index, waist circumference, physical activity, and the 4 health-related behaviors. Results: For each outcome of interest, considering the intervention uptake, the magnitude and direction of the intervention effect differed by country and by participants’ stage of readiness to change at baseline. Among those in the high intervention uptake category, reductions in systolic blood pressure were only achieved in Peru, whereas fruit and vegetable consumption also showed reductions among those who were at the maintenance stage at baseline in Argentina and Guatemala. Conclusions: Designing interventions oriented toward improving health-related lifestyle behaviors may benefit from recognizing baseline readiness to change and issues in implementation uptake.Fil: Carrillo-Larco, Rodrigo M.. Universidad Peruana Cayetano Heredia; Perú. Imperial College London; Reino UnidoFil: Jiwani, Safia S.. Universidad Peruana Cayetano Heredia; PerúFil: Diez Canseco, Francisco. Universidad Peruana Cayetano Heredia; PerúFil: Kanter, Rebecca. Institute of Nutrition of Central America and Panama; Guatemala. Universidad de Chile; ChileFil: Beratarrechea, Andrea Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Institute for Clinical Effectiveness and Health Policy; ArgentinaFil: Irazola, Vilma. Institute for Clinical Effectiveness and Health Policy; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramirez Zea, Manuel. Institute of Nutrition of Central America and Panama; GuatemalaFil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Martinez, Homero. Nutrition International; Canadá. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Miranda, J. Jaime. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú. Universidad Peruana Cayetano Heredia; PerúFil: Alasino, Adrían. Funprecal; ArgentinaFil: Budiel Moscoso, Berneth Nuris. Universidad Peruana Cayetano Heredia; PerúFil: Carrara, Carolina. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Espinoza Surichaqui, Jackelyn. Universidad Peruana Cayetano Heredia; PerúFil: Giardini, Gimena. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Guevara, Jesica. Institute of Nutrition of Central America And Panama Guatemala; GuatemalaFil: Morales Juárez, Analí. Institute of Nutrition of Central America And Panama Guatemala; GuatemalaFil: Lázaro Cuesta, Lorena. Funprecal; ArgentinaFil: Lewitan, Dalia. Institute For Clinical Effectiveness And Health Policy; ArgentinaFil: Palomares Estrada, Lita. Universidad Peruana Cayetano Heredia; PerúFil: Martínez Ramírez, Carla. Universidad Peruana Cayetano Heredia; PerúFil: de la Cruz, Gloria Robles. Universidad Peruana Cayetano Heredia; PerúFil: Salguero, Julissa. Institute Of Nutrition Of Central America And Panama Guatemala; GuatemalaFil: Saravia Drago, Juan Carlos. Universidad Peruana Cayetano Heredia; PerúFil: Urtasún, María. Institute For Clinical Effectiveness And Health Policy; ArgentinaFil: Zavala Loayza, José Alfredo. Universidad Peruana Cayetano Heredia; Per

Bacterial Toxicity of Potassium Tellurite: Unveiling an Ancient Enigma

Biochemical, genetic, enzymatic and molecular approaches were used to demonstrate, for the first time, that tellurite (TeO(3) (2−)) toxicity in E. coli involves superoxide formation. This radical is derived, at least in part, from enzymatic TeO(3) (2−) reduction. This conclusion is supported by the following observations made in K(2)TeO(3)-treated E. coli BW25113: i) induction of the ibpA gene encoding for the small heat shock protein IbpA, which has been associated with resistance to superoxide, ii) increase of cytoplasmic reactive oxygen species (ROS) as determined with ROS-specific probe 2′7′-dichlorodihydrofluorescein diacetate (H(2)DCFDA), iii) increase of carbonyl content in cellular proteins, iv) increase in the generation of thiobarbituric acid-reactive substances (TBARs), v) inactivation of oxidative stress-sensitive [Fe-S] enzymes such as aconitase, vi) increase of superoxide dismutase (SOD) activity, vii) increase of sodA, sodB and soxS mRNA transcription, and viii) generation of superoxide radical during in vitro enzymatic reduction of potassium tellurite