Genomic epidemiology of SARS-CoV-2 δ sublineages of the second wave of 2021 in Antioquia, Colombia / Epidemiología genómica de los sublinajes δ del virus SARS-CoV-2 de la segunda ola de COVID en Antioquia en el 2021.

Introduction. During the development of the SARS-CoV-2 pandemic in Antioquia, we experienced epidemiological peaks related to the α, É£, ß, ƛ, and δ variants. δ had the highest incidence and prevalence. This lineage is of concern due to its clinical manifestations and epidemiological characteristics. A total of 253 δ sublineages have been reported in the PANGOLIN database. The sublineage identification through genomic analysis has made it possible to trace their evolution and propagation. Objective. To characterize the genetic diversity of the different SARS-CoV-2 δ sublineages in Antioquia and to describe its prevalence. Materials and methods. We collected sociodemographic information from 2,675 samples, and obtained 1,115 genomes from the GISAID database between July 12th, 2021, and January 18th, 2022. From the analyzed genomes, 515 were selected because of their high coverage values (>90%) to perform phylogenetic analysis and to infer allele frequencies of mutations of interest. Results. We characterized 24 sublineages. The most prevalent was AY.25. Mutations of interest as L452R, P681R, and P681H were identified in this sublineage, comprising a frequency close to 0.99. Conclusions. This study identified that the AY.25 sublineage has a transmission advantage compared to the other δ sublineages. This attribute may be related to the presence of the L452R and P681R mutations associated in other studies with higher evasion of the immune system and less efficacy of drugs against SARS-CoV-2.

Introducción. Durante el desarrollo de la pandemia por SARS-CoV-2 en Antioquia se presentaron picos epidemiológicos relacionados con las variantes α, É£, ß, ƛ y δ, donde δ tuvo la mayor incidencia y prevalencia. Este linaje se considera una variante de preocupación dadas las manifestaciones clínicas que desencadena y sus características epidemiológicas. Se han informado 253 sublinajes δ en la base de datos PANGOLIN. La identificación de estos sublinajes mediante análisis genómico ha permitido rastrear su evolución y propagación. Objetivo. Caracterizar la diversidad genética de los diferentes sublinajes δ de SARSCoV-2 en Antioquia y determinar su prevalencia. Materiales y métodos. Se recopiló información sociodemográfica de 2.675 muestras y de 1.115 genomas del repositorio GISAID entre el 12 de julio de 2021 y el 18 de enero de 2022. Se seleccionaron 501 por su alto porcentaje de cobertura (>90 %) para realizar análisis filogenéticos e inferencia de frecuencias alélicas de mutaciones de interés. Resultados. Se caracterizaron 24 sublinajes donde el más prevalente fue AY.25. En este sublinaje se identificaron mutaciones de interés como L452R, P681R y P681H, que comprendían una frecuencia cercana a 0,99. Conclusiones. Este estudio permitió identificar que el sublinaje AY.25 tiene una ventaja de transmisión en comparación con los otros sublinajes δ. Esto puede estar relacionado con la presencia de las mutaciones L452R y P681R que en otros estudios se han visto asociadas con una mayor transmisibilidad, evasión del sistema inmunitario y menor eficacia de los medicamentos contra SARS-CoV-2.

Implications of analytical nanoscience in pharmaceutical and biomedical fields: A critical view.

This review summarizes recent progress performed in the design and application of analytical tools and methodologies using nanomaterials for pharmaceutical analysis, and specifically new nanomedicines at distinct phases of development and translation from preclinical to clinical stages. Over the last 10-15 years, a growing number of studies have utilized various nanomaterials, including carbon-based, metallic nanoparticles, polymeric nanomaterials, materials based on biological molecules, and composite nanomaterials as tools for improving the analysis of pharmaceutical products. New and more complex nanomaterials are currently being explored to influence different stages of the analytical process. These materials provide unique properties to support the extraction of analytes in complex samples, increase the selectivity and efficiency of chromatographic separations, and improve the analytical properties of many sensor applications. Indeed, nanomaterials, including electrochemical detection approaches and biosensing, are expanding at a remarkable rate. Furthermore, the analytical performance of numerous approaches to determine drugs in different matrices can be significantly improved in terms of precision, detection limits, selectivity, and time of analysis. However, the quality control and metrological characterization of the currently synthesized nanomaterials still depend on the development of new and improved analytical methodologies, and the application of specific and improved instrumentation. Therefore, there is still much to explore about the properties of nanomaterials which need to be determined even more precisely and accurately.

Real-world clinical remission of severe asthma with benralizumab in Spanish adults with severe asthma.

OBJECTIVE: Patients with severe eosinophilic asthma experience high risk of exacerbations and reduced quality of life. Benralizumab, a monoclonal antibody binding to IL-5 receptor α subunit, is an approved drug for its treatment. The objective was to describe clinical remission after benralizumab prescription in routine clinical practice. METHODS: Retrospective multicenter study with data from four hospitals in Valencian Community (Spain) with asthma units between 2019 and 2020. Data was gathered at baseline and after 12 months. We considered clinical remission after 1 year if the patient remained without exacerbations and use of systemic corticosteroids and with good clinical control and normal lung function. RESULTS: Data from 139 patients was gathered. At the 12-month follow-up, 44.1% were in clinical remission, since 84.0%, 77.5%, 51.0% and 95.5% of patients did not experience exacerbations, had total asthma control test score of ≥20, prebronchodilator FEV1 of ≥80% and did not use systemic corticosteroids. A significant reduction of long-acting muscarinic antagonists (p = 0.0001), leukotriene receptor antagonists (p = 0.0326), oral corticosteroids (p < 0.0001) and short-acting beta agonists (p = 0.0499) was observed. Baseline factors with greatest individual influence on clinical remission were employment situation, tobacco use, comorbidity number, eosinophil value, number of exacerbations, FEV1, emergency visit number, and ACT, MiniAQLQ and TAI scores. Final analysis of multiple logistic regression indicated that having baseline FEV1 value below 80% increases remission chance 9.7 times a year compared to FEV1 >80%. CONCLUSION: Clinical remission after treatment with benralizumab is achievable in a high percentage of patients with severe asthma eosinophilia not controlled in real life.

Target enrichment sequencing coupled with GWAS identifies MdPRX10 as a candidate gene in the control of budbreak in apple.

The timing of floral budbreak in apple has a significant effect on fruit production and quality. Budbreak occurs as a result of a complex molecular mechanism that relies on accurate integration of external environmental cues, principally temperature. In the pursuit of understanding this mechanism, especially with respect to aiding adaptation to climate change, a QTL at the top of linkage group (LG) 9 has been identified by many studies on budbreak, but the genes underlying it remain elusive. Here, together with a dessert apple core collection of 239 cultivars, we used a targeted capture sequencing approach to increase SNP resolution in apple orthologues of known or suspected A. thaliana flowering time-related genes, as well as approximately 200 genes within the LG9 QTL interval. This increased the 275 223 SNP Axiom® Apple 480 K array dataset by an additional 40 857 markers. Robust GWAS analyses identified MdPRX10, a peroxidase superfamily gene, as a strong candidate that demonstrated a dormancy-related expression pattern and down-regulation in response to chilling. In-silico analyses also predicted the residue change resulting from the SNP allele associated with late budbreak could alter protein conformation and likely function. Late budbreak cultivars homozygous for this SNP allele also showed significantly up-regulated expression of C-REPEAT BINDING FACTOR (CBF) genes, which are involved in cold tolerance and perception, compared to reference cultivars, such as Gala. Taken together, these results indicate a role for MdPRX10 in budbreak, potentially via redox-mediated signaling and CBF gene regulation. Moving forward, this provides a focus for developing our understanding of the effects of temperature on flowering time and how redox processes may influence integration of external cues in dormancy pathways.

High resolution mass spectrometry-based screening for the comprehensive investigation of organic micropollutants in surface water and wastewater from Pasto city, Colombian Andean highlands.

The complexity of the aquatic environment scenario, including the impact of urban wastewater, together with the huge number of potential hazardous compounds that may be present in waters, makes the comprehensive characterization of the samples an analytical challenge, particularly in relation to the presence of organic micropollutants (OMPs). Nowadays, the potential of high-resolution mass spectrometry (HRMS) for wide-scope screening in environmental samples is out of question. Considering the physicochemical characteristics of OMPs, the coupling of liquid (LC) and gas chromatography (GC) to HRMS is mandatory. In this work, we have explored the combined use of LC and GC coupled to Quadrupole-Time-of-Flight Mass Spectrometry (QTOF MS) for screening of surface water and wastewater samples from Pasto (Nariño), a town of the Colombian Andean highlands (average altitude 2527 m), located in an important agricultural area. The upper basin of the Pasto River is impacted by phytosanitary products used in different crops, whereas the domestic wastewater is directly discharged into the river without any treatment, enhancing the anthropogenic impact on the water quality. The OMP searching was made by target (standards available) and suspect (without standards) approaches, using home-made databases containing >2000 compounds. Up to 15 pesticides (7 insecticides, 6 fungicides and 2 herbicides) were identified in the sampling point of the Pasto River up to the town, while no pharmaceuticals were found at this site, illustrating the impact of agriculture practices. On the contrary, 14 pharmaceuticals (7 antibiotics and 3 analgesics, among others) were found in river samples collected in the middle and down to the town sites, revealing the impact of the urban population. Interestingly, some transformation products, including metabolites, such as carbofuran-3-hydroxy and 4-acetylamino antipyrine were identified in the screening. Based on these data, future monitoring will apply target quantitative LC-MS/MS methods for the most relevant compounds identified.

Pharmacogenomic biomarker information on drug labels of the Spanish Agency of Medicines and Sanitary products: evaluation and comparison with other regulatory agencies.

This work aimed to analyse the pharmacogenetic information in the Spanish Drug Regulatory Agency (AEMPS) Summary of Products Characteristics (SmPC), evaluating the presence of pharmacogenetic biomarkers, as well as the associated recommendations. A total of 55.4% of the 1891 drug labels reviewed included information on pharmacogenetic biomarker(s). Pharmacogenomic information appears most frequently in the "antineoplastic and immunomodulating agents", "nervous system", and "cardiovascular system" Anatomical Therapeutic Chemical groups. A total of 509 different pharmacogenetic biomarkers were found, of which CYP450 enzymes accounted for almost 34% of the total drug-biomarker associations evaluated. A total of 3679 drug-biomarker pairs were identified, 102 of which were at the 1A level (PharmGKB® classification system), and 33.33% of these drug-pharmacogenetic biomarker pairs were assigned to "actionable PGx", 12.75% to "informative PGx", 4.9% to "testing recommended", and 4.9% to "testing required". The rate of coincidence in the assigned PGx level of recommendation between the AEMPS and regulatory agencies included in the PharmGKB® Drug Label Annotations database (i.e., the FDA, EMA, SWISS Medic, PMDA, and HCSC) ranged from 45% to 65%, being 'actionable level' the most frequent. On the other hand, discrepancies between agencies did not exceed 35%. This study highlights the presence of relevant pharmacogenetic information on Spanish drug labels, which would help avoid interactions, toxicity, or lack of treatment efficacy.

Saccharomyces cerevisiae biofactory to produce naringenin using a systems biology approach and a bicistronic vector expression strategy in flavonoid production.

IMPORTANCE: Flavonoids are a group of compounds generally produced by plants with proven biological activity, which have recently beeen recommended for the treatment and prevention of diseases and ailments with diverse causes. In this study, naringenin was produced in adequate amounts in yeast after in silico design. The four genes of the involved enzymes from several organisms (bacteria and plants) were multi-expressed in two vectors carrying each two genes linked by a short viral peptide sequence. The batch kinetic behavior of the product, substrate, and biomass was described at lab scale. The engineered strain might be used in a more affordable and viable bioprocess for industrial naringenin procurement.

CRISPR-Cas9-mediated somatic correction of a one-base deletion in the Ugt1a gene ameliorates hyperbilirubinemia in Crigler-Najjar syndrome mice.

(AAV)-mediated episomal gene replacement therapy for monogenic liver disorders is currently limited in pediatric settings due to the loss of vector DNA, associated with hepatocyte duplication during liver growth. Genome editing is a promising strategy leading to a permanent and specific genome modification that is transmitted to daughter cells upon proliferation. Using genome targeting, we previously rescued neonatal lethality in mice with Crigler-Najjar syndrome. This rare monogenic disease is characterized by severe neonatal unconjugated hyperbilirubinemia, neurological damage, and death. Here, using the CRISPR-Staphylococcus aureus Cas9 (SaCas9) platform, we edited the disease-causing mutation present in the Ugt1a locus of these mice. Newborn mice were treated with two AAV8 vectors: one expressing the SaCas9 and single guide RNA, and the other carrying the Ugt1a homology regions with the corrected sequence, while maintained in a temporary phototherapy setting rescuing mortality. We observed a 50% plasma bilirubin reduction that remained stable for up to 6 months. We then tested different Cas9:donor vector ratios, with a 1:5 ratio showing the greatest efficacy in lowering plasma bilirubin, with partial lethality rescue when more severe, lethal conditions were applied. In conclusion, we reduced plasma bilirubin to safe levels and partially rescued neonatal lethality by correcting the mutant Ugt1a1 gene of a Crigler-Najjar mouse model.

Improved Methods for Fourier-Based Microwave Imaging.

Fourier-based imaging has been widely adopted for microwave imaging thanks to its efficiency in terms of computational complexity without compromising image resolution. Together with other backpropagation imaging algorithms like delay-and-sum (DAS), they are based on a far-field approach to the electromagnetic expression relating to fields and sources. To improve the accuracy of these techniques, this contribution presents a modified version of the well-known Fourier-based algorithm by taking into account the field radiated by the Tx/Rx antennas of the microwave imaging system. The impact on the imaged targets is discussed, providing a quantitative and qualitative analysis. The performance of the proposed method for subsampled microwave imaging scenarios is compared against other well-known aliasing mitigation methods.

Necrosis esofágica aguda (esófago negro) asociado a neoplasias digestivas / Acute esophageal necrosis (black esophagus) associated with digestive neoplasms

INTRODUCCIÓN. La necrosis esofágica aguda es un síndrome raro que se caracteriza endoscópicamente por una apariencia negra circunferencial irregular o difusa de la mucosa esofágica intratorácica, la afectación es generalmente del esófago distal y la transición abrupta de mucosa normal en la unión gastroesofágica, con extensión proximal variable. CASOS. Se presentan dos casos con diferentes comorbiliades, presentación de signos y síntomas, antecedentes y tratamiento, teniendo en común el diagnóstico a través de endoscopía digestiva alta. RESULTADOS. Caso clínico 1: tratamiento clínico basado en hidratación, suspensión de vía oral, omeprazol intravenoso y sucralfato; mala evolución clínica caracterizada por: disfagia, intolerancia oral y recurrencia del sangrado digestivo alto, se realiza colocación de gastrostomía endoscópica. Caso clínico 2: esófago con mucosa con fibrina y parches de necrosis extensa, se realiza compensación tanto de foco infeccioso pulmonar como hidratación y nutrición, en estudios complementarios se observa masa colónica, con estudio histopatológico confirmatorio de adenocarcinoma de colon en estado avanzado. DISCUSIÓN. La esofagitis necrotizante aguda es una entidad inusual, de baja prevalencia e incidencia, asociada con estados de hipoperfusión sistémica y múltiples comorbilidades que favorezcan un sustrato isquémico. Al revisar los reportes de casos que hay en la literatura médica, los casos que reportamos se correlaciona con las características clínicas, epidemiológicas, endoscópicas y factores de riesgo causales de la enfermedad. La presentación clínica más frecuente es el sangrado digestivo alto, que se debe correlacionar con el hallazgo endoscópico clásico. Nuestro primer caso reportado termina con la colocación de una gastrostomía para poder alimentarse. CONCLUSIÓN. El pronóstico de la necrosis esofágica aguda es malo y se requiere un alto índice de sospecha clínica y conocimiento de esta infrecuente patología para un diagnóstico temprano y un manejo oportuno. Se requiere una evaluación por endoscopia digestiva alta. Es una causa de sangrado gastrointestinal que conlleva tasas altas de mortalidad, principalmente en adultos mayores frágiles. El reconocimiento temprano y la reanimación agresiva son los principios fundamentales para un mejor resultado de la enfermedad.

INTRODUCTION. Acute esophageal necrosis is a rare syndrome that is characterized endoscopically by an irregular or diffuse circumferential black appearance of the intrathoracic esophageal mucosa, the involvement is generally of the distal esophagus and the abrupt transition of normal mucosa at the gastroesophageal junction, with variable proximal extension. CASES. Two cases are presented with different comorbidities, presentation of signs and symptoms, history and treatment, having in common the diagnosis through upper gastrointestinal endoscopy. RESULTS. Clinical case 1: clinical treatment based on hydration, oral suspension, intravenous omeprazole and sucralfate; poor clinical evolution characterized by: dysphagia, oral intolerance and recurrence of upper digestive bleeding, endoscopic gastrostomy placement was performed. Clinical case 2: esophagus with mucosa with fibrin and patches of extensive necrosis, compensation of both the pulmonary infectious focus and hydration and nutrition is performed, in complementary studies a colonic mass is observed, with a confirmatory histopathological study of colon adenocarcinoma in an advanced state. DISCUSSION. Acute necrotizing esophagitis is an unusual entity, with low prevalence and incidence, associated with states of systemic hypoperfusion and multiple comorbidities that favor an ischemic substrate. When reviewing the case reports in the medical literature, the cases we report correlate with the clinical, epidemiological, endoscopic characteristics and causal risk factors of the disease. The most common clinical presentation is upper gastrointestinal bleeding, which must be correlated with the classic endoscopic finding. Our first reported case ends with the placement of a gastrostomy to be able to feed. CONCLUSION. The prognosis of acute esophageal necrosis is poor and a high index of clinical suspicion and knowledge of this rare pathology is required for early diagnosis and timely management. Evaluation by upper gastrointestinal endoscopy is required. It is a cause of gastrointestinal bleeding that carries high mortality rates, mainly in frail older adults. Early recognition and aggressive resuscitation are the fundamental principles for a better outcome of the disease.

Underwater polypectomy at the appendiceal orifice in a patient on anticoagulation.

A 78-year-old male on warfarin for deep venous thrombosis is referred to us for resection of a sessile polyp in the cecum. A high-definition Fujifilm BL-7000 processor, virtual chromoendoscopy, and EC-760ZP-V/L magnifying endoscope were used. Diathermy source, ERBE VIO 3. Auto cut mode, Effect 5, 80 watts, and Soft coagulation mode, Effect 5, 60 watts. Underwater polypectomy ensued with resection in two fragments. The resection bed was invaginated into the appendiceal orifice, hence no other measures were considered to prevent delayed bleeding. No complications were reported. The histopathological study found a tubulovillous adenoma with lesion-free borders.

Two novel symbiovars of Bradyrhizobium yuanmingense, americaense and caribense, the symbiovar tropici of Bradyrhizobium pachyrhizi and the symbiovar cajani of Bradyrhizobium cajani are microsymbionts of the legume Cajanus cajan in Dominican Republic.

Cajanus cajan L. (guandul) is commonly cultivated in Dominican Republic where this legume is a subsistence crop. Here we identified through MALDI-TOF MS several rhizobial strains nodulating C. cajan in two Dominican locations as Bradyrhizobium yuanmingense. The phylogenetic analysis of recA and glnII housekeeping genes showed that these strains belong to a wide cluster together with the type strain of B. yuanmingense and other C. cajan nodulating strains previously isolated in Dominican Republic. The comparison of genomes from strains representative of different lineages within this cluster support the existence of several genospecies within B. yuanmingense, which is the major microsymbiont of C. cajan in Dominican Republic where it is also nodulated by Bradyrhizobium cajani and Bradyrhizobium pachyrhizi. The analysis of the symbiotic nodC gene showed that the C. cajan nodulating strains from the B. yuanmingense complex belong to two clusters with less than 90% similarity between them. The strains from these two clusters showed nodC gene similarity values lower than 90% with respect to the remaining Bradyrhizobium symbiovars and then they correspond to two new symbiovars for which we propose the names americaense and caribense. The results of the nodC gene analysis also showed that C. cajan is nodulated by the symbiovar tropici, which has been found by first time in this work within the species Bradyrhizobium pachyrhizi. These results confirmed the high promiscuity degree of C. cajan, which is also nodulated by the symbiovar cajani of Bradyrhizobium cajani in Dominican Republic.

Diferencias de sexo asociadas al suicidio y años potenciales de vida perdidos: un estudio retrospectivo

Objetivo: Identificar las diferencias de sexo asociadas a los años potenciales de vida perdidos por suicidio en el departamento de Nariño, periodo 2005-2019. Metodología: Estudio de tipo descriptivo observacional y retrospectivo, en el que se analizaron 1686 certificados de defunción por suicidio de hombres y mujeres en el departamento de Nariño, identificados en el Departamento Nacional Administrativo de Estadística. Resultados: En el periodo 2005-2019, se observaron 1212 suicidios en hombres y 474 en mujeres. Estas se suicidaron a edades más bajas que aquellos. El 50,5 % de los hombres habían cursado básica primaria, y el 46,0 % de las mujeres, básica secundaria. El mayor número de casos de suicidios en hombres y mujeres se presentaron en el área urbana (51,2 % y 45,1 % respectivamente). El envenenamiento fue el mecanismo de suicidio más utilizado por las mujeres (66,7 %), y para los hombres, el mayor porcentaje (41,7) correspondió al ahorcamiento. La tendencia anual de muertes por suicidio fue mayor en hombres que en mujeres. En aquellos, la tasa de suicidio se situó por encima de 4,5 suicidios por 100 000 habitantes, mientras que, en ellas, se mantuvo por debajo de 3,0. Conclusiones: Hubo un aumento en la tendencia de muertes en el periodo de tiempo analizado y el riesgo de morir por suicidio en el hombre fue 3,9 veces el riesgo de morir en una mujer. El estudio contempla importantes aspectos para ser abordados en la prevención del suicidio.

Objective: To identify the sex differences associated with the potential years of life lost due to suicide in the department of Nariño, from 2005 to 2019. Methodology: Descriptive, observational and retrospective study, in which 1686 death certificates by suicide of men and women in the department of Nariño, identified in the National Administrative Department of Statistics, were analyzed. Results: From 2005 to 2019, 1,212 suicide cases of men were observed and 474 of women. Women committed suicide at younger ages than men. 50.5% of the men had completed primary school, and 46.0% of the women, secondary school. The highest number of suicide cases of men and women occurred in the urban area (51.2% and 45.1% respectively). Poisoning was the suicide mechanism most used by women (66.7%), and for men, the highest percentage (41.7) corresponded to hanging. The annual trend of deaths by suicide was higher in men than in women. For men, the suicide rate was above 4.5 suicides per 100,000 inhabitants, while for women, it remained below 3.0. Conclusions: There was an increase in the trend of deaths in the period analyzed and the risk of dying by suicide in men was 3.9 times the risk of dying by suicide in women. The study contemplates important aspects to be addressed in suicide prevention.

Objetivo: Identificar as diferenças de sexo associadas aos anos potenciais de vida perdidos por suicídio no departamento de Nariño, no período 2005-2019. Metodologia: Estudo de tipo descritivo observacional e retrospectivo, em que foram analisados 1686 certificados de óbito por suicídio de homens e mulheres no departamento de Nariño, identificados no Departamento Nacional Administrativo de Estatística. Resultados: No período de 2005-2019, observaram-se 1212 suicídios em homens e 474 em mulheres. Elas suicidaram-se em idades menores do que eles. O 50,5% dos homens cursaram o ensino fundamental, e o 46% das mulheres o ensino médio. O maior número de casos de suicídios em homens e mulheres apresentou-se na área urbana (51,2% y 45,1%, respectivamente). O envenenamento foi o mecanismo de suicídio mais utilizado pelas mulheres (66,7%), e para os homens, a maior percentagem (41,7%) correspondeu ao enforcamento. A tendência anual de mortes por suicídio foi maior em homens do que em mulheres. Neles, a taxa de suicídio esteve por cima de 4,5 suicídios por 100.000 habitantes, enquanto nelas se manteve abaixo de 3,0. Conclusões: Houve um aumento na tendência de mortes no período de tempo analisado e o risco de morrer por suicídio no caso dos homens foi 3,9 vezes o risco de morrer de uma mulher. O estudo contempla aspectos importantes a serem abordados na prevenção do suicídio.

Fibronectin extra domain a limits liver dysfunction and protects mice during acute inflammation.

Background and aim: The primary transcript of fibronectin (FN) undergoes alternative splicing to generate different isoforms, including FN containing the Extra Domain A (FN_EDA+), whose expression is regulated spatially and temporarily during developmental and disease conditions including acute inflammation. The role of FN_EDA+ during sepsis, however, remains elusive. Methods: Mice constitutively express the EDA domain of fibronectin (EDA+/+); lacking the FN EDA domain (EDA-/-) or with a conditional ablation of EDA + inclusion only in liver produced FN (alb-CRE+EDA floxed mice) thus expressing normal plasma FN were used. Systemic inflammation and sepsis were induced by either LPS injection (70 mg/kg) or by cecal ligation and puncture (CLP) Neutrophils isolated from septic patients were tested for neutrophil binding ability. Results: We observed that EDA+/+ were protected toward sepsis as compared to EDA-/- mice. Also alb-CRE+EDA floxed mice presented reduced survival, thus indicating a key role for EDA in protecting toward sepsis. This phenotype was associated with improved liver and spleen inflammatory profile. Ex vivo experiments showed that neutrophils bind to a larger extent to an FN_EDA + coated surface as compared to FN, thus potentially limiting their over-reactivity. Conclusions: Our study demonstrates that the inclusion of the EDA domain in fibronectin dampens the nflammatoryi consequences of sepsis.

Impact of Coaching on the Development of Personal and Social Competences among Secondary School Students.

In this study, the impact of school coaching in Spain on the dimensions that comprise the effective personality construct and the development of those dimensions among secondary school students is analyzed. Differences relating to the variables of gender, course year/age, and the state/private sector of each educational center are specified. A longitudinal study employing a quasi-experimental methodology was conducted with a sample of 310 students in attendance at 6 educational centers within the Community of Madrid, Spain; the study cohort comprised 156 (50.3%) male students and 154 (49.7%) female students. The effective personality questionnaire in secondary education was used for the pre- and post-intervention evaluations, as well as to conduct an open survey once the program had ended. The students who attended the six-session intervention expressed high degrees of satisfaction. Despite the brevity of each session (45-60 min), a slight non-significant improvement was observed in the experimental group relative to the control group in the dimensions that were studied (p > 0.05). Regarding gender, the program worked better with male rather than with female students. It was also more effective within state-aided than in state schools.

Enhancing Wound Healing: A Novel Topical Emulsion Combining CW49 Peptide and Lavender Essential Oil for Accelerated Regeneration and Antibacterial Protection.

Wound healing is a complex process involving blood cells, extracellular matrix, and parenchymal cells. Research on biomimetics in amphibian skin has identified the CW49 peptide from Odorrana grahami, which has been demonstrated to promote wound regeneration. Additionally, lavender essential oil exhibits anti-inflammatory and antibacterial activities. Given these considerations, we propose an innovative emulsion that combines the CW49 peptide with lavender oil. This novel formulation could serve as a potent topical treatment, potentially fostering the regeneration of damaged tissues and providing robust antibacterial protection for skin wounds. This study investigates the physicochemical properties, biocompatibility, and in vitro regenerative capacity of the active components and the emulsion. The results show that the emulsion possesses appropriate rheological characteristics for topical application. Both the CW49 peptide and lavender oil exhibit high viability in human keratinocytes, indicating their biocompatibility. The emulsion induces hemolysis and platelet aggregation, an expected behavior for such topical treatments. Furthermore, the lavender-oil emulsion demonstrates antibacterial activity against both Gram-positive and Gram-negative bacterial strains. Finally, the regenerative potential of the emulsion and its active components is confirmed in a 2D wound model using human keratinocytes. In conclusion, the formulated emulsion, which combines the CW49 peptide and lavender oil, shows great promise as a topical treatment for wound healing. Further research is needed to validate these findings in more advanced in vitro models and in vivo settings, potentially leading to improved wound-care management and novel therapeutic options for patients with skin injuries.

Determinantes sociales asociados a la seguridad alimentaria y nutricional en hogares de mujeres con exceso de peso de Girardot, Cundinamarca (Colombia) / Approach from social determinants to food and nutritional security in households of overweight women in Girardot

Fundamentos: los resultados de la Encuesta Nacional de Situación Nutricional (ENSIN) de los últimos 15 años muestran un marcado aumento en el exceso de peso en adultos. En 2015, el 59,6% de las mujeres entre 18 y 64 años presentó exceso de peso. El objetivo fue analizar la situación de seguridad alimentaria y nutricional (SAN) en un grupo de hogares del municipio de Girardot - Cundinamarca, a partir del referencial de los determinantes sociales de la SAN y la equidad social. Métodos: estudio cuantitativo transversal analítico realizado entre 2019 y 2020. Se realizó recolección de variables sociodemográficas, inseguridad alimentaria en el hogar (INSAH), estrategias de afrontamiento de ésta y frecuencia de consumo de alimentos mediante 4 instrumentos tipo encuesta en 20 mujeres adultas con exceso de peso residentes en Girardot (Colombia) de hogares urbanos de los estratos 1 y 2. Resultados: se encontró asociación estadísticamente significativa entre la decisión de uso de los ingresos económicos y la estrategia de afrontamiento número 2, clasificadas como determinantes intermedios y la INSAH. Conclusiones: se identificaron la composición del hogar, el nivel educativo del jefe de hogar, la decisión de uso del dinero del hogar, entre otros, como determinantes sociales que agudizan las inequidades en la situación alimentaria y nutricional de los hogares estudiados. (AU)

Background: According to the National Survey of the Nutritional Situation (ENSIN) results, during the last 15 years the obesity in adults has been sharply increasing. In fact, 59,6% of women between 18 and 64 years old were overweight in 2015. The objective was to analyze the Food and Nutrition Security Situation (SAN) within urban households in Girardot - Cundinamarca, based on the social determinants of SAN and social equality Methods: Analytical cross-sectional quantitative study. This paper used a data collection system of background variables, such as food insecurity (INSAH), the coping strategies used by the INSAH and the eating frequency, all this information was collected by interviewing the people using 4 different types of polls. Results: Analytical cross-sectional quantitative study. This paper used a data collection system of background variables, such as food insecurity, the coping strategies used by the INSAH and the eating frequency, all this information was collected by interviewing the people using 4 different types of polls. Conclusions: It was identified the nuclear family composition, the head of the household educational level, the use of money decisions at home among others. As social determinants that contribute to intensifying the inequality in the food and nutritional status in the households of study. (AU)

A Holistic Approach from Systems Biology Reveals the Direct Influence of the Quorum-Sensing Phenomenon on Pseudomonas aeruginosa Metabolism to Pyoverdine Biosynthesis.

Computational modeling and simulation of biological systems have become valuable tools for understanding and predicting cellular performance and phenotype generation. This work aimed to construct, model, and dynamically simulate the virulence factor pyoverdine (PVD) biosynthesis in Pseudomonas aeruginosa through a systemic approach, considering that the metabolic pathway of PVD synthesis is regulated by the quorum-sensing (QS) phenomenon. The methodology comprised three main stages: (i) Construction, modeling, and validation of the QS gene regulatory network that controls PVD synthesis in P. aeruginosa strain PAO1; (ii) construction, curating, and modeling of the metabolic network of P. aeruginosa using the flux balance analysis (FBA) approach; (iii) integration and modeling of these two networks into an integrative model using the dynamic flux balance analysis (DFBA) approximation, followed, finally, by an in vitro validation of the integrated model for PVD synthesis in P. aeruginosa as a function of QS signaling. The QS gene network, constructed using the standard System Biology Markup Language, comprised 114 chemical species and 103 reactions and was modeled as a deterministic system following the kinetic based on mass action law. This model showed that the higher the bacterial growth, the higher the extracellular concentration of QS signal molecules, thus emulating the natural behavior of P. aeruginosa PAO1. The P. aeruginosa metabolic network model was constructed based on the iMO1056 model, the P. aeruginosa PAO1 strain genomic annotation, and the metabolic pathway of PVD synthesis. The metabolic network model included the PVD synthesis, transport, exchange reactions, and the QS signal molecules. This metabolic network model was curated and then modeled under the FBA approximation, using biomass maximization as the objective function (optimization problem, a term borrowed from the engineering field). Next, chemical reactions shared by both network models were chosen to combine them into an integrative model. To this end, the fluxes of these reactions, obtained from the QS network model, were fixed in the metabolic network model as constraints of the optimization problem using the DFBA approximation. Finally, simulations of the integrative model (CCBM1146, comprising 1123 reactions and 880 metabolites) were run using the DFBA approximation to get (i) the flux profile for each reaction, (ii) the bacterial growth profile, (iii) the biomass profile, and (iv) the concentration profiles of metabolites of interest such as glucose, PVD, and QS signal molecules. The CCBM1146 model showed that the QS phenomenon directly influences the P. aeruginosa metabolism to PVD biosynthesis as a function of the change in QS signal intensity. The CCBM1146 model made it possible to characterize and explain the complex and emergent behavior generated by the interactions between the two networks, which would have been impossible to do by studying each system's individual components or scales separately. This work is the first in silico report of an integrative model comprising the QS gene regulatory network and the metabolic network of P. aeruginosa.

Multifunctional magnetoliposomes as drug delivery vehicles for the potential treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Therefore, development of novel technologies and strategies to treat PD is a global health priority. Current treatments include administration of Levodopa, monoamine oxidase inhibitors, catechol-O-methyltransferase inhibitors, and anticholinergic drugs. However, the effective release of these molecules, due to the limited bioavailability, is a major challenge for the treatment of PD. As a strategy to solve this challenge, in this study we developed a novel multifunctional magnetic and redox-stimuli responsive drug delivery system, based on the magnetite nanoparticles functionalized with the high-performance translocating protein OmpA and encapsulated into soy lecithin liposomes. The obtained multifunctional magnetoliposomes (MLPs) were tested in neuroblastoma, glioblastoma, primary human and rat astrocytes, blood brain barrier rat endothelial cells, primary mouse microvascular endothelial cells, and in a PD-induced cellular model. MLPs demonstrated excellent performance in biocompatibility assays, including hemocompatibility (hemolysis percentages below 1%), platelet aggregation, cytocompatibility (cell viability above 80% in all tested cell lines), mitochondrial membrane potential (non-observed alterations) and intracellular ROS production (negligible impact compared to controls). Additionally, the nanovehicles showed acceptable cell internalization (covered area close to 100% at 30 min and 4 h) and endosomal escape abilities (significant decrease in lysosomal colocalization after 4 h of exposure). Moreover, molecular dynamics simulations were employed to better understand the underlying translocating mechanism of the OmpA protein, showing key findings regarding specific interactions with phospholipids. Overall, the versatility and the notable in vitro performance of this novel nanovehicle make it a suitable and promising drug delivery technology for the potential treatment of PD.

The double burden of malnutrition and gross motor development in infants: A cross-sectional study.

OBJECTIVE: The objective of the present work was to study the relationship between the double burden of malnutrition and gross motor development in infants. METHOD: ology: Sample included 5900 infants under 24 months of age, participants of the ENSANUT-ECU study. To evaluate nutritional status, we calculated z-scores for body mass index/age (BAZ) and height/age (HAZ). Six gross motor milestones were considered: sitting without-support, crawling, standing and walking with-support, standing and walking without-support. Data was analysed using logistic regression models in R. RESULTS: Independently form age, sex and other socio-economic factors, the probability of achieving three gross motor milestones was significantly lower among chronically undernourished infants compared to their peers: sitting without-support, crawling, and walking without-support. Compared to no malnourished infants the probability of sitting without-support at six months was 10% lower for chronically undernourished infants (0.70, 95%CI [0.64-0.75]; 0.60, 95%CI [0.52-0.67]; respectively). The probability of crawling at eight months and walking without-support at 12 months were also significantly lower among chronically undernourished infants (0.62, 95%CI [0.58-0.67]); 0.25, 95%CI [0.20-0.30]; respectively) in comparison to no malnourished infants (0.67, 95%CI [0.63-0.72]); 0.29, 95%CI [0.25-0.34]; respectively). Obesity/overweight was not associated with the achievement of gross motor milestones, except for sitting without-support. Chronically undernourished infants with low or high BMI/age were generally delayed in the achievement of gross motor milestones than their peers. CONCLUSIONS: Chronic undernutrition is related to delayed gross motor development. Public health measures are needed to be implemented to prevent the double burden of malnutrition and its detrimental effects on infant development.