Giotto Suite: a multi-scale and technology-agnostic spatial multi-omics analysis ecosystem.

Emerging spatial omics technologies continue to advance the molecular mapping of tissue architecture and the investigation of gene regulation and cellular crosstalk, which in turn provide new mechanistic insights into a wide range of biological processes and diseases. Such technologies provide an increasingly large amount of information content at multiple spatial scales. However, representing and harmonizing diverse spatial datasets efficiently, including combining multiple modalities or spatial scales in a scalable and flexible manner, remains a substantial challenge. Here, we present Giotto Suite, a suite of open-source software packages that underlies a fully modular and integrated spatial data analysis toolbox. At its core, Giotto Suite is centered around an innovative and technology-agnostic data framework embedded in the R software environment, which allows the representation and integration of virtually any type of spatial omics data at any spatial resolution. In addition, Giotto Suite provides both scalable and extensible end-to-end solutions for data analysis, integration, and visualization. Giotto Suite integrates molecular, morphology, spatial, and annotated feature information to create a responsive and flexible workflow for multi-scale, multi-omic data analyses, as demonstrated here by applications to several state-of-the-art spatial technologies. Furthermore, Giotto Suite builds upon interoperable interfaces and data structures that bridge the established fields of genomics and spatial data science, thereby enabling independent developers to create custom-engineered pipelines. As such, Giotto Suite creates an immersive ecosystem for spatial multi-omic data analysis.

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.

Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype.

The application of tissue-engineering approaches to human induced pluripotent stem (hiPS) cells enables the development of physiologically relevant human tissue models for in vitro studies of development, regeneration, and disease. However, the immature phenotype of hiPS-derived cardiomyocytes (hiPS-CMs) limits their utility. We have developed a protocol to generate engineered cardiac tissues from hiPS cells and electromechanically mature them toward an adult-like phenotype. This protocol also provides optimized methods for analyzing these tissues' functionality, ultrastructure, and cellular properties. The approach relies on biological adaptation of cultured tissues subjected to biomimetic cues, applied at an increasing intensity, to drive accelerated maturation. hiPS cells are differentiated into cardiomyocytes and used immediately after the first contractions are observed, when they still have developmental plasticity. This starting cell population is combined with human dermal fibroblasts, encapsulated in a fibrin hydrogel and allowed to compact under passive tension in a custom-designed bioreactor. After 7 d of tissue formation, the engineered tissues are matured for an additional 21 d by increasingly intense electromechanical stimulation. Tissue properties can be evaluated by measuring contractile function, responsiveness to electrical stimuli, ultrastructure properties (sarcomere length, mitochondrial density, networks of transverse tubules), force-frequency and force-length relationships, calcium handling, and responses to ß-adrenergic agonists. Cell properties can be evaluated by monitoring gene/protein expression, oxidative metabolism, and electrophysiology. The protocol takes 4 weeks and requires experience in advanced cell culture and machining methods for bioreactor fabrication. We anticipate that this protocol will improve modeling of cardiac diseases and testing of drugs.

Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors.

Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native heart impedes investigations of CF biology and their role in disease. Human pluripotent stem cells (hPSCs) provide a highly renewable and genetically defined cell source, but efficient methods to generate CFs from hPSCs have not been described. Here, we show differentiation of hPSCs using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-CFs. The hPSC-CFs resemble native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFß1 and angiotensin II. Furthermore, hPSC-CFs exhibit a more embryonic phenotype when compared to fetal and adult primary human CFs. Co-culture of hPSC-CFs with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties of the cardiomyocytes compared to co-culture with dermal fibroblasts. The hPSC-CFs provide a powerful cell source for research, drug discovery, precision medicine, and therapeutic applications in cardiac regeneration.

Clinical effectiveness of pre-treatment with chlorhexidine in adhesive dental restorations: systematic review and meta-analysis / Eficacia clínica del pretratamiento con clorhexidina en restauraciones dentales adhesivas: revisión sistemática y metanálisis

Objective: To determine, by means of a systematic review and meta-analysis, the clinical effectiveness of pre-treatment with chlorhexidine (CHX) in adhesive dental restorations. Material and Methods: A literature search was conducted until February 2020, in the biomedical databases: Pubmed, Embase, Scielo, Science Direct, Scopus, SIGLE, LILACS, Google Scholar and the Cochrane Central Registry of Clinical Trials. The selection criteria of the studies were defined, which were: randomized and controlled clinical trials, without language and time restrictions, and reporting the clinical effects (retention, marginal discoloration, marginal adaptation, postoperative sensitivity and secondary caries) of pre-CHX treatment in adhesive dental restorations. Study risk of bias was analyzed using the Cochrane Handbook of Systematic Reviews of Interventions. Results:The search strategy resulted in six articles of which five entered a meta-analysis. The studies reported that there was no difference in retention, marginal discoloration, marginal adaptation, postoperative sensitivity, and secondary caries from pre-treatment with CHX in adhesive dental restorations. Conclusion: The reviewed literature suggests that pretreatment with CHX does not influence the clinical effectiveness in adhesive dental restorations.

Resumen: Antecedentes: la pandemia de COVID-19 ha desatado un ataque sin precedentes contra la humanidad en todo el mundo. El escenario en Bangladesh empeora día a día, y todos los aspectos de la sociedad están observando su impacto. Los profesionales de la salud corren un mayor riesgo de contraer la enfermedad mientras atienden a los pacientes. Objetivo: El objetivo de la investigación es explorar el conocimiento, la conciencia y las prácticas de los dentistas registrados con respecto a la epidemiología y transmisión de COVID-19 durante el rápido brote de este virus altamente contagioso en Bangladesh. Material y Métodos: Se realizó una encuesta transversal basada en la web entre los dentistas inscritos con su número de registro único válido del Consejo Médico y Dental de Bangladesh (BMDC). Se distribuyó un cuestionario estructurado entre los dentistas a través de diferentes plataformas de redes sociales. Un total de 184 dentistas participaron en la encuesta entre marzo y abril de 2020. Se realizó tanto análisis descriptivo como análisis de regresión logística multivariable. Resultados: La edad media de los odontólogos fue de 31,75 años, con una desviación estándar de 6,5 años. Aproximadamente el 29,3% de los dentistas habían completado su título de posgrado y el 76% de ellos se dedicaba a la práctica privada en el momento de la recopilación de datos. En comparación con los dentistas con educación universitaria, los dentistas con educación de posgrado tienen tres veces (OR = 3,1, IC del 95%: 1,2 - 7,9 y más de 5 veces (OR = 5,3, IC del 95%: 1,2 - 23,3) más probabilidades de tener) mejores conocimientos y prácticas hacia COVID-19 respectivamente. Los dentistas de 26 a 30 años tienen menos probabilidades de tener buenas prácticas que los dentistas más jóvenes (OR: .1; IC del 95%: .01 - .5). Sin embargo, los dentistas con menos de cinco años de experiencia tienen 10,3 (1,6 - 68,9) veces más probabilidades de tener buenas prácticas en comparación con los dentistas con más experiencia. Conclusión: La mayoría de los dentistas de Bangladesh han demostrado un buen conocimiento, conciencia y práctica con respecto a COVID-19. Recomendamos que las autoridades sanitarias, las organizaciones profesionales y los hospitales coordinen y lleven a cabo una formación avanzada obligatoria sobre enfermedades infecciosas para todos los dentistas en ejercicio del país.

The STR polymorphism (AAAAT)n within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe.

The STR (AAAAT)n within intron 1 of the TP53 locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans, and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126/7 (bp/copies of the repeat), 131/8 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R(ST)) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within Europeans.

[Racial mix of the panamanian population]. / La mezcla racial de la población panameña.

The racial admixture of a target population can be ascertained by quantifying the contribution to the genetic pool of each of its components (ancestral populations), which could be two, three or more. The racial admixture is of importance for the understanding of results derived from biomedical and anthropological studies. The main objective of this investigation is to determine the population frequencies of genetic systems ABO and Rh and to use these data to calculate the racial admixture of the country and of each sample province, fitting a trihybrid model. To achieve this, the Krieger method, implemented by the computer program Mistura 3, was applied to phenotypic data of systems ABO and Rh in a sample of 4,202 subjects born in seven provinces. In the general population of Panama, 38.72% of genes from the genetic pool have an African origin, 35.87%, an Amerindian origin and 25.40%, a Caucasian origin. In the province of Cocle we found a contribution of 16.47% of African genes, 55.25% of Amerindian genes and 28.28% of Caucasian genes. The province of Colon presents 69.34% of African genes, 25.00% of Amerindian genes and 5.65% of Caucasian genes. In contrast, Chiriquí presents 5.56% of African genes, 50.63% of Amerindian genes and 43.80% of Caucasian genes. The province of Herrera is characterized by the following proportions: 58.45% African genes, 28.44% Amerindian genes and 13.11% Caucasian genes. In the province of Los Santos there is a 62.29% African contribution, a 14.35% Amerindian contribution and a 22.72% Caucasian one. In the province of Panama there is a 57.01%, 26.25% and 16.74% contribution of African, Amerindian and Caucasian genes, respectively. Finally, in Veraguas a contribution of 18.59% of African genes, 44.29% of Amerindian genes and 37.12% of Caucasian genes was found.

The STR polymorphism (AAAAT)n within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe

The STR (AAAAT)n within intron 1 of the TP53 locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans, and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126/7 (bp/copies of the repeat), 131/8 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R(ST)) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within Europeans.

Citogenética y citoquímica de pacientes con leucemias en dos hospitales neotropicales / Citogenetics and citochemistry of leukemia patients in two neotropical hospitals

A cytogenetic and/or cytochemical study was performed in 166 individuals with leukemia or related disorders, in two major Costa Rican hospitals. In those patients treated at an adult`s (14 years old and over), acute leukemias represented 66 porcent of all cases. In that hospital the most frequent types of disorders were, in decreasing order: ANLL(>M1), ALL, CML (all of them showed the Ph chromosome) and MDS. In the cases fron a children`s hospital (<14 years old) acute leukemias were 98 porcent. Among them the order of frequency was: ALL (70 porcent): ALL-1(84 porcent), ALL-2(16 porcent) and ANLL (27 porcent): M5a>M3>M4>M5b. In ALL 85 porcent were type B and occurred mostly in women while 15 porcent of them were type T and more frequent in males. There was 5.6 porcent infant leukemia, which presented a similar number of acute lymphoids and myeloids. The cytogenetic pattern was similar among Costa Rica and other tropical and temperate countries. Key words: Leukemia cytogenetics, acute lymphocytic leukemia, acute nonlymphocitic leukemia, chronic granulocytic leukemia