Overexpression of miR-25 Downregulates the Expression of ROBO2 in Idiopathic Intellectual Disability.

Idiopathic intellectual disability (IID) encompasses the cases of intellectual disability (ID) without a known cause and represents approximately 50% of all cases. Neural progenitor cells (NPCs) from the olfactory neuroepithelium (NEO) contain the same information as the cells found in the brain, but they are more accessible. Some miRNAs have been identified and associated with ID of known etiology. However, in idiopathic ID, the effect of miRNAs is poorly understood. The aim of this study was to determine the miRNAs regulating the expression of mRNAs that may be involved in development of IID. Expression profiles were obtained using NPC-NEO cells from IID patients and healthy controls by microarray. A total of 796 miRNAs and 28,869 mRNAs were analyzed. Several miRNAs were overexpressed in the IID patients compared to controls. miR-25 had the greatest expression. In silico analysis showed that ROBO2 was the target for miR-25, with the highest specificity and being the most down-regulated. In vitro assay showed an increase of miR-25 expression induced a decrease in ROBO2 expression. In neurodevelopment, ROBO2 plays a crucial role in episodic learning and memory, so its down-regulation, caused by miR-25, could have a fundamental role in the intellectual disability that, until now, has been considered idiopathic.

Assembly and phylogeographical analysis of novel Taenia solium mitochondrial genomes suggest stratification within the African-American genotype.

BACKGROUND: Taenia solium is a parasite of public health concern, causing human taeniasis and cysticercosis. Two main genotypes have been identified: Asian and African-American. Although characterizing T. solium genotypes is crucial to understanding the genetic epidemiology of its diseases, not much is known about the differences between T. solium mitochondrial genomes from different genotypes. Also, little is known about whether genotypes are further subdivided. Therefore, this study aimed to identify a set of point mutations distributed throughout the T. solium mitochondrial genome that differentiate the African-American from the Asian genotype. Another objective was to identify whether T. solium main genotypes are further stratified. METHODS: One Mexican and two Peruvian T. solium mitochondrial genomes were assembled using reads available in the NCBI Sequence Read Archive and the reference genome from China as a template. Mutations with respect to the Chinese reference were identified by multiple genome alignment. Jensen-Shannon and Grantham scores were computed for mutations in protein-coding genes to evaluate whether they affected protein function. Phylogenies by Bayesian inference and haplotype networks were constructed using cytochrome c oxidase subunit 1 and cytochrome b from these genomes and other isolates to infer phylogeographical relationships. RESULTS: A set of 31 novel non-synonymous point mutations present in all genomes of the African-American genotype were identified. These mutations were distributed across the mitochondrial genome, differentiating the African-American from the Asian genotype. All occurred in non-conserved protein positions. Furthermore, the analysis suggested a stratification of the African-American genotypes into an East African and a West African sublineage. CONCLUSIONS: A novel set of 31 non-synonymous mutations differentiating the main T. solium genotypes was identified. None of these seem to be causing differences in mitochondrial protein function between parasites of the two genotypes. Furthermore, two sublineages within the African-American genotype are proposed for the first time. The presence of the East African sublineage in the Americas suggests an underestimated connection between East African and Latin American countries that might have arisen in the major slave trade between Portuguese Mozambique and the Americas. The results obtained here help to complete the molecular epidemiology of the parasite.

First Report of Antibiotic Resistance Markers cfiA and nim Among Bacteroides fragilis Group Strains in Ecuadorian Patients.

In recent years, increasing resistance of Bacteroides fragilis to several antibiotics has been reported in different countries. The aim of this study was to evaluate the antibiotic resistance profiles of Bacteroides spp. isolated from clinical samples by phenotypic and molecular methods. A total of 40 nonrepetitive isolates of the B. fragilis group were studied from 2018 to 2019. The species was identified by API 20A system. The minimum inhibitory concentrations (MICs) were determined by Sensititre anaerobe MIC plate. The presence of the nim and cfiA genes was checked by conventional PCR. The association between genes and insertion sequence (IS) was performed by whole genome sequencing. Eleven isolates were categorized as metronidazole-resistant and only 2 isolates harbored the nim gene. Five isolates were imipenem-resistant, but cfiA gene was detected in two isolates. cfiA gene was closely related to the cfiA-4 allele and associated with IS614B. The nim gene was not related to any nim gene type and was considered a new variant named nimL. IS612 was found upstream of nimL gene. In view of the scarcity of data on B. fragilis, there is a need to surveil antibiotic resistance levels and molecular mechanisms to implement better antimicrobial therapies against this important group of bacteria.

An Overview of the Use and Applications of Limosilactobacillus fermentum in Broiler Chickens.

The implementation of government regulations on antibiotic use, along with the public's concern for drug resistance, has strengthened interest in developing alternatives not only aimed at preserving animal production but also at reducing the effects of pathogenic infections. Probiotics, in particular, are considered microorganisms that induce health benefits in the host after consumption of adequate amounts; they have been established as a potential strategy for improving growth, especially by stimulating intestinal homeostasis. Probiotics are commonly associated with lactic acid bacteria, and Limosilactobacillus fermentum is a well-studied species recognized for its favorable characteristics, including adhesion to epithelial cells, production of antimicrobial compounds, and activation of receptors that prompt the transcription of immune-associated genes. Recently, this species has been used in animal production. Different studies have shown that the application of L. fermentum strains not only improves the intestinal ecosystem but also reduces the effects caused by potentially pathogenic microorganisms. These studies have also revealed key insights into the mechanisms behind the actions exerted by this probiotic. In this manuscript, we aim to provide a concise overview of the effects of L. fermentum administration on broiler chicken health and performance.

Opposite Auxin Dynamics Determine the Gametophytic and Embryogenic Fates of the Microspore.

The microspore can follow two different developmental pathways. In vivo microspores follow the gametophytic program to produce pollen grains. In vitro, isolated microspores can be reprogrammed by stress treatments and follow the embryogenic program, producing doubled-haploid embryos. In the present study, we analyzed the dynamics and role of endogenous auxin in microspore development during these two different scenarios, in Brassica napus. We analyzed auxin concentration, cellular accumulation, the expression of the TAA1 auxin biosynthesis gene, and the PIN1-like efflux carrier gene, as well as the effects of inhibiting auxin biosynthesis by kynurenine on microspore embryogenesis. During the gametophytic pathway, auxin levels and TAA1 and PIN1-like expression were high at early stages, in tetrads and tapetum, while they progressively decreased during gametogenesis in both pollen and tapetum cells. In contrast, in microspore embryogenesis, TAA1 and PIN1-like genes were upregulated, and auxin concentration increased from the first embryogenic divisions. Kynurenine treatment decreased both embryogenesis induction and embryo production, indicating that auxin biosynthesis is required for microspore embryogenesis initiation and progression. The findings indicate that auxin exhibits two opposite profiles during these two microspore developmental pathways, which determine the different cell fates of the microspore.

Erythrose inhibits the progression to invasiveness and reverts drug resistance of cancer stem cells of glioblastoma.

Glioblastoma (GBM) is the most frequent brain cancer and more lethal than other cancers. Characteristics of this cancer are its high drug resistance, high recurrence rate and invasiveness. Invasiveness in GBM is related to overexpression of matrix metalloproteinases (MMPs) which are mediated by wnt/ß-catenin and induced by the activation of signaling pathways extracellularly activated by the cytokine neuroleukin (NLK) in cancer stem cells (CSC). Therefore, in this work we evaluated the effect of the tetrose saccharide, erythrose (Ery), a NLK inhibitor of invasiveness and drug sensitization in glioblastoma stem cells (GSC). GSC were obtained from parental U373 cell line by a CSC phenotype enrichment protocol based on microenvironmental stress conditions such as hypoxia, hipoglycemia, drug exposition and serum starvation. Enriched fraction of GSC overexpressed the typical markers of brain CSC: low CD133+ and high CD44; in addition, epithelial to mesenchyme transition (EMT) markers and MMPs were increased several times in GSC vs. U373 correlating with higher invasiveness, elongated and tubular mitochondrion and temozolomide (TMZ) resistance. IC50 of Ery was found at nM concentration and at 24 h induced a severe diminution of EMT markers, MMPs and invasiveness in GSC. Furthermore, the phosphorylation pattern of NLK after Ery exposition also was affected. In addition, when Ery was administered to GSC at subIC50, it was capable of reverting TMZ resistance at concentrations innocuous to non-tumor cancer cells. Moreover, Ery added daily induced the death of all GSC. Those findings indicated that the phytodrug Ery could be used as adjuvant therapy in GBM.

Neuropsychological intervention in attention and visuospatial skills in two patients with Williams syndrome with different types of genetic deletion.

Williams Syndrome (WS) is a neurodevelopmental disorder with a distinctive physical, cognitive, and behavioral profile caused by a microdeletion in the q11.23 region of chromosome 7. The neuropsychological profile of WS is characterized by intellectual disability, hypersociability, and deficits, especially in attention and visuospatial skills. Our objective was to assess the effectiveness of a neuropsychological intervention program in attention and visuospatial skills in two patients with WS (aged 7 and 13 years old) with different types of deletion (1.5 and 1.8 Mb). Cognitive, behavioral, and adaptive abilities were evaluated through various neuropsychological tests and scales; the neuropsychological intervention program was subsequently applied, and we assessed its effectiveness. Both patients initially presented significant deficits in attention and visuospatial skills. After the program, we found improvements in attention and visuospatial skills. In addition, both patients had significant clinical advances and changes in adaptive behaviors (social and self-care). These findings suggest that this intervention program could improve attention processes, visuospatial skills, and some aspects of adaptive behavior in patients with WS, regardless of deletion size. Although the sample was small, limiting the generalizability of the results, we believe this program could be a helpful resource for professionals working with individuals with WS.

Voices of the Costa Rican scientific diaspora: Policy lessons from a decade of experiences from our scientists abroad.

Scientific diasporas have been identified as valuable resources to strengthen science, technology, and innovation in their countries of origin. In this context, our paper seeks to contribute by addressing the following research questions: What are the main features of the Costa Rican scientific diaspora, and what policy lessons can be extracted from their experiences abroad? Toward this goal, we analyzed ten years of diaspora perspectives as collected by TicoTal, an online database and network of Costa Rican scientists studying and working abroad created by the National Academy of Sciences (ANC) in 2010. Our study reveals the main features of the Costa Rican scientific diaspora using 121 interviews published over a ten-year period: we identified the academic areas in which the diaspora has specialized, the countries where they were trained, their current location, the most frequent funding mechanisms and sources that enabled professional opportunities abroad, the level of engagement and collaboration they maintain with the Costa Rican STI ecosystem, along with the incentives they consider important to support and harness the potential of this community to advance STI goals in the country. Results from this analysis can inform national policies and investment strategies in R&D infrastructure and resources, by providing a roadmap to engage with scientific diasporas and benefit from their training and talent, as well as guide future scholarship and exchange programs.

La electrólisis percutánea intratisular: una revisión sistemática / Percutaneous intratissue electrolysis: a systematic review

La electrólisis percutánea intratisular es un procedimiento terapéutico tecnológico mínimamente invasivo para el tratamiento de lesiones en el sistema musculoesquelético mediante inflamación controlada y fagocitosis para recuperar el tejido afectado. Acerca de esta, se realizó un análisis de la producción científica publicada de 2014 a 2021. El estudio se realizó por medio de una revi-sión bibliográfica sistémica siguiendo la metodología PRISMA, que incluyó el uso de fuentes de información en las bases científicas: PubMed, SciencieDirect, EuropePMC, ResearchGate, Sage Journal, Thiem Connect y PHysiotherapy evidence database (PEdro). Previamente al procesa-miento de los datos, los documentos encontrados fueron sometidos diversos criterios de selec-ción. Los investigadores concluyeron que la electrólisis percutánea intratisular resulta un trata-miento efectivo para el tratamiento de tendinopatías crónicas, cuando se realiza combinado con un programa de ejercicios enfocado en la progresión de las cargas.

This work presents an analysis of the scientific production developed between 2014 and 2021 on percutaneous intratissue electrolysis. The objective is to analyze the bibliograpHy on the diffe-rent EPI interventions. The study was carried out through a systemic review following a methodological process according to PRISMA using various sources for the collection of information, such as: Pubmed, Scienciedirect, Europe PMC, Hindawi, Cochrane, Sage Journal, Thiem Connect, Pedro, Puerta Of the investigation. Selection and quality criteria were applied to these documents, with a subsequent analysis using qualitative techniques. In conclusion, intratissue percutaneous electrolysis turns out to be a favorable tool in the treatment of chronic tendinopathies as long as it is combined with an exercise program focused on load progression.

Pulvinar Sign, Stroke and Their Relationship with Fabry Disease: A Systematic Review and Metanalysis.

Background: Fabry disease (FD) is the second most common lysosomal storage disorder. This disorder affects multiple systems that include the cardiac, renal, and nervous system. The pulvinar sign (PS) is a relatively common sign seen in patients with FD. The PS is a bilateral, symmetrical pulvinar high signal relative to the signal intensity seen on unenhanced T1-weighted brain MR imaging. Methods: We conducted a systematic review with metanalysis to analyze the pool prevalence of the disorder. We used the Moose Guidelines and PRISMA Protocol for this systematic review and Robins 1 to access the BIAS of the study. To analyze the pool prevalence, we used "Open Meta-Analysis" software for analyzing the study. We used "Review Manager 5.4" to analyze the odds ratio between patients with and without the PS and patients with and without stroke among patients with FD. Results: We gather 12 studies from 2003 to 2021 for the analysis of this study. The pool prevalence of the study was 0.146 (0.076−0.217) (62/385 cases) with a 95% CI (0.0945−0.415) (p < 0.01). The prevalence was much higher in men (59 cases) than in women (3 cases). There was no relationship between the pulvinar sign and patients with stroke among patients with Fabry disease. Odds ratio 1.97 95% CI (0.35−11.21), p = 0.44; Tau2 = 0.77. There seems to be a correlation with renal failure (RF), but there were very few studies to conduct a metanalysis with RF. Conclusions: The prevalence of the PS among all studies was 23.9%; the prevalence of this sign is higher among males. We found that FD patients who had strokes did not have higher odds of presenting with the Pulvinar Sign than the FD patients who did not suffer a stroke. Patients with renal failure and FD seem to have a higher tendency to have the PS, but there were not enough studies to analyze that theory. Overall, we think the pulvinar sign has a poor prognostic value in patients with Fabry's disease.

Compatibility of mycorrhiza-induced resistance with viral and bacterial entomopathogens in the control of Spodoptera exigua in tomato.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are soil-borne microorganisms that establish mutualistic associations with roots of most terrestrial plants. This symbiosis results in nutritional and defensive benefits to the host plant, usually conferring protection against biotic stresses, but its indirect impact on third trophic levels is still unknown. In the present work, we explore whether the symbiosis of tomato plants with Funneliformis mosseae (and/or exposition to herbivory) influences the interaction of the generalist pest Spodoptera exigua (Lepidoptera: Noctuidae) with bacterial (Bacillus thuringiensis) and viral (baculovirus, SeMNPV) natural entomopathogens. RESULTS: Symbiosis with AMF and previous herbivory reduces the relative growth of S. exigua, increases its susceptibility to a sublethal dose of B. thuringiensis and has positive or neutral impact on the lethality of SeMNPV. Reduction of the phenoloxidase activity, a marker of the insect immune response, was associated with the larval feeding on plant material previously exposed to herbivory but not to the AMF. In addition, no changes in the insect gut microbiota could be associated with the observed changes in larval growth and susceptibility to the entomopathogens. CONCLUSION: Our findings provide the first evidence of compatibility of AMF symbiosis in tomato with the use of bacterial and viral entomopathogens, contributing to the development of novel approaches to combine the beneficial effect of AMF and entomopathogens in biological pest control. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Efectos de la experiencia cultural en la percepción de excelencia e impacto económico de los asistentes al Festival Internacional Cervantino / Effects of cultural experience on the perception of excellence and economic impact of the attendees at the International Cervantino Festival

Resumen El Festival Internacional Cervantino (FIC) es el evento turístico cultural más importante de la ciudad de Guanajuato, que atrae cada año a miles de visitantes. El objetivo de esta investigación fue determinar los factores que forman la experiencia de los asistentes al FIC, así como su relación con la percepción de la excelencia y del impacto económico, mediante la adaptación de un modelo estructural teórico basado en el modelo escandinavo de "Skot-Hansen y Linko y Silvanto". Se empleó una metodología cuantitativa, sustentada en un modelo de ecuaciones estructurales, basado en una encuesta hecha de manera no aleatoria por conveniencia a 709 visitantes en 2017. Los resultados identificaron que los factores ilustración, empoderamiento y entretenimiento, provocaron en los asistentes del festival, una experiencia memorable que anima, profundiza y enaltece de forma significativa sus vidas, aspecto que no siempre se ha valorado en este tipo de actividades. Además, la experiencia influye en la excelencia apreciada, impactando en la percepción de la calidad y profesionalismo de la organización y el nivel artístico del FIC. Los asistentes de este festival también percibieron que la excelencia apreciada en los factores de ilustración, empoderamiento y entretenimiento, beneficia la imagen positiva de Guanajuato; al fortalecerla como destino turístico, lo que repercute económicamente. Se concluye que el FIC logra buenas prácticas y políticas culturales, lo que es arduo de alcanzar y puede ser un argumento a favor de su propuesta.

Abstract The International Cervantino Festival (FIC) is the most important tourist cultural event in the city of Guanajuato since it attracts thousands of visitors every year. The objective of this research was to determine the factors that constitute the experience of FIC's attendees' as well as its relationship towards the perception of excellence and economic impact. A structural equation theoretical model based on the Scandinavian "Skot-Hansen and Linko and Silvanto" model was adapted for that purpose. A quantitative methodology was used, supported by a structural equations model, based on a survey with a non-random convenience sample of 709 visitors in 2017. Results identified that factors such as illustration, empowerment and entertainment produced a memorable experience among FIC attendees that encourages, deepens and heightens their lives in a meaningful way, an aspect that had not always been valued in these kinds of activities. Additionally, the experience also has an impact on perceived excellence, which impacts the perception of FIC's quality, professionalism, organization and artistic level. FIC's attendees also perceived that the excellence within illustration, empowerment and entertainment benefit Guanajuato's positive image strengthening the city as a touristic destination that leads to positive economic repercussions. It is concluded that FIC achieves good practices and cultural policies, a fact that is difficult to achieve and that can be an argument in favor of its cultural proposal.

Medical empathy in medical students in Madrid: A proposal for empathy level cut-off points for Spain.

This study evaluates the degree of empathy among medical students and its influencing factors at three critical moments of their degree studies (beginning of first year and end of third and sixth years) as well as establishes low-, medium-, and high-empathy cut-off points to obtain valid and reliable results that can be extrapolated to the general population. This cross-sectional study of the eight (public and private) medical schools in the province of Madrid, used an electronic questionnaire with the Jefferson Scale of Empathy (JSE), Medical Student Well-Being Index, and other independent characteristics as measuring instruments. Of the 2,264 student participants, 1,679 (74.0%) were women, with a 50.7% participation rate. No significant differences were found in empathy levels by academic year. Regarding range, percentile and cut-off point tables were established to identify students with high, medium, and low empathy levels. Women (p<0.001), volunteer workers (p<0.001), and those preferring general specialties (internal medicine, psychiatry, pediatrics, or family medicine) scored higher on the JSE (p<0.02). Moreover, 41.6% presented high level of psychological distress. Women reported a lower well-being level and a higher risk of psychological distress (p = 0.004). In sum, the empathy of medical students in Madrid did not differ among the three critical moments of their university studies. The established cut-off points could be taken into account when accessing the medical degree and identifying students with low levels of empathy to implement curricular interventions to rectify this perceived deficiency. There was a high percentage of medical students with high levels of psychological distress.

Tsukamurella inchonensis isolated from catheter of an Ecuadorian patient with hemodialysis.

We report a case of catheter-related bloodstream infection by Tsukamurella inchonensis, identified using 16S rRNA gene sequencing, in a patient with arterial hypertension for 20 years and chronic kidney disease in hemodialysis since 08/07/2019. To our knowledge, this is the first case of T. inchonensis in Ecuador.

Overcoming the unprecedented: Micro, small and medium hospitality enterprises under COVID-19.

The sudden irruption of COVID-19 has paralysed, even devastated, numerous industries. Academic and industry publications also convey the destructive impacts of this phenomenon on hospitality and tourism businesses. While business owners and managers are still constrained by unpredictability, restrictions, and ongoing uncertainty, those vying to continue will need to build their adaptive skill repertoire to cope with the crisis-related regime. This study is primarily concerned with businesses' adaptation phase from owners/managers' viewpoints, including how they manage and envision a future coexistence with COVID-19 threats. Drawing on an international sample of owners/managers of hospitality and tourism businesses, and considering the foundations of the dynamic capabilities framework, eight dimensions emerged from the findings. Five of these, persevering, dynamic, austere restrictions, business environment, and stakeholder, strongly suggest the relevance of reconfiguring, a cluster of dynamic capabilities. Together, the dimensions demonstrate participants' strong commitment to navigate through the threat while pursuing socioeconomic sustainability.

Consenso de leucemia mieloide aguda en México / Mexican consensus in acute myeloid leukemia in Mexico

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Abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.