SUCCESSFUL BK VIRUS-SPECIFIC T CELLS THERAPY IN A KIDNEY TRANSPLANT RECIPIENT WITH PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY.

The strategy for Progressive Multifocal Leukoencephalopathy (PML) in Solid Organ Transplant recipients primarily focuses on reducing immunosuppressive therapy. However, this approach offers limited efficacy and carries a high risk of graft loss. Here, we present the case of a 64-year-old male kidney transplant recipient with a high degree of immunosuppression who developed PML in October 2022. Despite standard reduction of immunosuppressive therapy, the patient's condition continued to deteriorate, as evidenced by worsening neurological symptoms and increasing JC virus DNA levels in cerebrospinal fluid. This prompted the innovative use of BKPyV -specific T Cells-(BKPyV -VST) therapy, given the genetic similarities between BK and JC viruses. Infusion of third-party donor BKPyV -VST resulted in clinical stabilization, significant reduction in JCV DNA levels, and the emergence of a JC virus-specific T cell response, as observed in ELISpot assays and TCRß sequencing. This represents the first case report of successful third-party BKPyV -VST -specific therapy in a kidney recipient presenting PML, without graft-versus-host disease or graft dysfunction.

Fracture load of chairside CAD-CAM veneers fabricated with pre-and fully crystalized lithium disilicate ceramics.

PURPOSE: To evaluate the fracture load of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) veneers fabricated with two conventional pre-crystallized and two fully crystallized lithium disilicate ceramic materials. MATERIALS AND METHODS: Seventy-five chairside CAD-CAM veneers (15 specimens/group) for maxillary right central incisors were fabricated with different lithium disilicate brands: (1) IPS e.max CAD; (2) Amber Mill; (3) Cerec Tessera; (4) n!ce Straumann; and (5) GC Initial LiSi Block. Restorations were cemented with resin luting cement (Variolink Esthetic, Ivoclar) to 3D-printed resin dies. Bonded restorations received 5000 thermal cycles and then were loaded until fracture. Statistical analysis included One-Way ANOVA. RESULTS: Conventional pre-crystallized e.max CAD displayed the highest fracture load value (640 N), followed by fully-crystallized n!ce Straumann (547 N), pre-crystallized Cerec Tessera (503 N), pre-crystallized Amber Mill (476 N), respectively; fully-crystallized GC Initial LiSi Block (431 N) displayed the lowest values. When comparing the fracture load of recent lithium disilicate ceramic material to the e.max group, which acted as the control, significant differences were noted. The LiSi Block GC group, in particular, had considerably higher mean difference values (208.867, p < 0.001, 95% CI [89.63, 328.10]), as did the Amber Mill group (164.200, p = 0.002, 95% CI [44.96, 283.44]) and CEREC Tessera group (137.533, p = 0.016, 95% CI [18.30, 256.77]). The e.max and n!ce Straumann groups had no statistically significant differences in mean scores (92.933, p = 0.198, 95% CI [-26.30, 212.17]). These findings imply that the clinical performance of recent lithium disilicate veneers varies when compared to the e.max CAD group. CONCLUSIONS: The fracture load of chairside CAD-CAM lithium disilicate veneers for maxillary central incisors varies according to the type of ceramic brands. Conventional pre-crystallized e.max CAD displayed higher fracture load than the recent pre- and fully-crystallized lithium disilicate materials, emphasizing the significance of choosing the right product based on the desired clinical outcome.

Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene.

BACKGROUND: Biallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which structural variants (SVs) represent a common cause of disease. However, their identification using short-read sequencing (SRS) is not always feasible. Here, we conducted targeted long-read sequencing (T-LRS) using adaptive sampling of EYS on the MinION sequencing platform (Oxford Nanopore Technologies) to definitively diagnose an arRP family, whose affected individuals (n = 3) carried the heterozygous pathogenic deletion of exons 32-33 in the EYS gene. As this was a recurrent variant identified in three additional families in our cohort, we also aimed to characterize the known deletion at the nucleotide level to assess a possible founder effect. RESULTS: T-LRS in family A unveiled a heterozygous AluYa5 insertion in the coding exon 43 of EYS (chr6(GRCh37):g.64430524_64430525ins352), which segregated with the disease in compound heterozygosity with the previously identified deletion. Visual inspection of previous SRS alignments using IGV revealed several reads containing soft-clipped bases, accompanied by a slight drop in coverage at the Alu insertion site. This prompted us to develop a simplified program using grep command to investigate the recurrence of this variant in our cohort from SRS data. Moreover, LRS also allowed the characterization of the CNV as a ~ 56.4kb deletion spanning exons 32-33 of EYS (chr6(GRCh37):g.64764235_64820592del). The results of further characterization by Sanger sequencing and linkage analysis in the four families were consistent with a founder variant. CONCLUSIONS: To our knowledge, this is the first report of a mobile element insertion into the coding sequence of EYS, as a likely cause of arRP in a family. Our study highlights the value of LRS technology in characterizing and identifying hidden pathogenic SVs, such as retrotransposon insertions, whose contribution to the etiopathogenesis of rare diseases may be underestimated.

Implantation of a double allogeneic human engineered tissue graft on damaged heart: insights from the PERISCOPE phase I clinical trial.

BACKGROUND: In preclinical studies, the use of double allogeneic grafts has shown promising results in promoting tissue revascularization, reducing infarct size, preventing adverse remodelling and fibrosis, and ultimately enhancing cardiac function. Building upon these findings, the safety of PeriCord, an engineered tissue graft consisting of a decellularised pericardial matrix and umbilical cord Wharton's jelly mesenchymal stromal cells, was evaluated in the PERISCOPE Phase I clinical trial (NCT03798353), marking its first application in human subjects. METHODS: This was a double-blind, single-centre trial that enrolled patients with non-acute myocardial infarction eligible for surgical revascularization. Seven patients were implanted with PeriCord while five served as controls. FINDINGS: Patients who received PeriCord showed no adverse effects during post-operative phase and one-year follow-up. No significant changes in secondary outcomes, such as quality of life or cardiac function, were found in patients who received PeriCord. However, PeriCord did modulate the kinetics of circulating monocytes involved in post-infarction myocardial repair towards non-classical inflammation-resolving macrophages, as well as levels of monocyte chemoattractants and the prognostic marker Meteorin-like in plasma following treatment. INTERPRETATION: In summary, the PeriCord graft has exhibited a safe profile and notable immunomodulatory properties. Nevertheless, further research is required to fully unlock its potential as a platform for managing inflammatory-related pathologies. FUNDING: This work was supported in part by grants from MICINN (SAF2017-84324-C2-1-R); Instituto de Salud Carlos III (ICI19/00039 and Red RICORS-TERAV RD21/0017/0022, and CIBER Cardiovascular CB16/11/00403) as a part of the Plan Nacional de I + D + I, and co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (2021-SGR-01437).

Mechanochemical Encapsulation of Caffeine in UiO-66 and UiO-66-NH2 to Obtain Polymeric Composites by Extrusion with Recycled Polyamide 6 or Polylactic Acid Biopolymer.

The development of capsules with additives that can be added to polymers during extrusion processing can lead to advances in the manufacturing of textile fabrics with improved and durable properties. In this work, caffeine (CAF), which has anti-cellulite properties, has been encapsulated by liquid-assisted milling in zirconium-based metal-organic frameworks (MOFs) with different textural properties and chemical functionalization: commercial UiO-66, UiO-66 synthesized without solvents, and UiO-66-NH2 synthesized in ethanol. The CAF@MOF capsules obtained through the grinding procedure have been added during the extrusion process to recycled polyamide 6 (PA6) and to a biopolymer based on polylactic acid (PLA) to obtain a load of approximately 2.5 wt% of caffeine. The materials have been characterized by various techniques (XRD, NMR, TGA, FTIR, nitrogen sorption, UV-vis, SEM, and TEM) that confirm the caffeine encapsulation, the preservation of caffeine during the extrusion process, and the good contact between the polymer and the MOF. Studies of the capsules and PA6 polymer+capsules composites have shown that release is slower when caffeine is encapsulated than when it is free, and the textural properties of UiO-66 influence the release more prominently than the NH2 group. However, an interaction is established between the biopolymer PLA and caffeine that delays the release of the additive.

Comparison of Adhesion Performance of a Self-curing and a Light-curing Universal Adhesive to Various Dental Substrates and CAD/CAM Materials.

PURPOSE: To compare the adhesion of a self-curing (Tokuyama Universal Bond, TUB) and a light-curing (Scotchbond Universal, SBU) universal adhesive to CAD/CAM materials, enamel, and dentin. This study also assessed differences in enamel adhesion between self-etch vs selective etching modes, as well as immediate and long-term adhesion to dentin for both adhesives. MATERIALS AND METHODS: Shear bond strength (SBS) testing was used to assess adhesion to enamel, dentin, Lava Ultimate (LU), Vita Enamic (VE), IPS e.max CAD (LD), IPS e.max ZirCAD (3Y-Zir), and Lava Esthetic (5Y-Zir) (n = 10). Moreover, bonding to enamel in self-etch and selective etching modes (n = 10) as well as immediate and aged resin-dentin bond strength (24 h after bonding, after 100,000 thermal cycles [TC] and long-term storage) was evaluated using the microtensile bond-strength test (n = 30). Failure mode was also determined for the bonding to dentin. Statistical analyses consisted of one-way and two-way ANOVA with appropriate post-hoc Tukey-Kramer or two-sample t-tests, as well as the chi-squared or Fisher's exact test (α = 0.05). RESULTS: TUB and SBU universal adhesives presented similar bonding to LU, VE, 3Y-Zir, and 5Y-Zir. However, SBS for TUB was superior to SBU when bonding to lithium-disilicate glass-ceramic (IPS e.max CAD). SBU showed better adhesion to dentin and enamel when used in the self-etch mode, while TUB promoted strong bond strength to enamel in the selective etching mode. TUB after TC was the only aging condition that yielded a significant reduction in resin-dentin bond strength. CONCLUSION: In-vitro adhesion performance of the self-curing and light-curing universal adhesives varies depending on the dental substrate or CAD/CAM restorative material used for bonding.

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU) after Intake of Dietary Supplement.

INTRODUCTION: The pathogenesis of tubulointerstitial nephritis with uveitis syndrome (TINU) is thought to be an interplay between environmental and genetic factors leading to an inappropriate immune response. METHODS: Report of a clinical case. RESULTS: We present a case of TINU syndrome which meets the clinical and anatomopathological features according to the classification criteria of the standardization of uveitis nomenclature (SUN) working group. The only possible causal agent was found to be the intake of a nutritional supplement. CONCLUSION: Our case highlights the role of environmental factors as triggers for this disorder.

Dentin Degradation: From Tissue Breakdown to Possibilities for Therapeutic Intervention.

Purpose of the Review: Presently, dental materials science is driven by the search for new and improved materials that can trigger specific reactions from the affected tissue to stimulate repair or regeneration while interacting with the oral environment to promote or maintain oral health. In parallel, evidence from the past decades has challenged the exclusive role of bacteria in dentin tissue degradation in caries, questioning our understanding of caries etiopathogenesis. The goal of this review is to recapitulate the current evidence on the host and bacterial contributions to degradation, inflammation, and repair of the dentin-pulp complex in caries. Recent Findings: Contrasting findings attribute dentin breakdown to the activity of endogenous enzymes, such as matrix metalloproteinases (MMPs) and cathepsins, while the role of bacteria and their by-products in the destruction of dentin organic matrix and pulp inflammation has been for decades supported as an incontestable paradigm. Aiming to better understand the mechanisms involved in collagen degradation by host enzymes in caries, studies have showed that these proteinases are expressed in the mature dentin (i.e., after dentin formation) and become activated by the low pH in the acidic environment resulted by bacterial metabolism in caries. However, different host sources other than dentin-bound proteinases seem to also contribute to caries progression, such as saliva and pulp. Interestingly, studies evaluating pulp responses to bacteria invasion and inflammation in caries report higher levels of MMPs and cathepsins in inflamed tissue, but also showed MMP potential to resolve inflammation and stimulate wound healing. Notably, as reported for other tissues, MMPs exert dual roles in the dentin-pulp complex in caries, participating or regulating both degradative and reparative mechanisms. Summary: The specific roles of host and bacteria and their by-products in caries progression have yet to be clarified. The complex interactions between inflammation and repair in caries pose challenges to a clear understanding of the dentin-pulp complex responses and changes to bacteria invasion. However, it opens new venues for the development of novel therapies and dental biomaterials based on the modulation of specific mechanisms to favor tissue repair and healing.

Comparability exercise of critical quality attributes of clinical-grade human mesenchymal stromal cells from the Wharton's jelly: single-use stirred tank bioreactors versus planar culture systems.

BACKGROUND AIMS: The increasing demand of clinical-grade mesenchymal stromal cells (MSCs) for use in advanced therapy medicinal products (ATMPs) require a re-evaluation of manufacturing strategies, ensuring scalability from two-dimensional (2D) surfaces to volumetric (3D) productivities. Herein we describe the design and validation of a Good Manufacturing Practice-compliant 3D culture methodology using microcarriers and 3-L single-use stirred tank bioreactors (STRs) for the expansion of Wharton's jelly (WJ)-derived MSCs in accordance to current regulatory and quality requirements. METHODS: MSC,WJ were successfully expanded in 3D and final product characterization was in conformity with Critical Quality Attributes and product specifications previously established for 2D expansion conditions. RESULTS: After 6 days of culture, cell yields in the final product from the 3D cultures (mean 9.48 × 108 ± 1.07 × 107 cells) were slightly lower but comparable with those obtained from 2D surfaces (mean 9.73 × 108 ± 2.36 × 108 cells) after 8 days. In all analyzed batches, viability was >90%. Immunophenotype of MSC,WJ was highly positive for CD90 and CD73 markers and lacked of expression of CD31, CD45 and HLA-DR. Compared with 2D expansions, CD105 was detected at lower levels in 3D cultures due to the harvesting procedure from microcarriers involving trypsin at high concentration, and this had no impact on multipotency. Cells presented normal karyotype and strong immunomodulatory potential in vitro. Sterility, Mycoplasma, endotoxin and adventitious virus were negative in both batches produced. CONCLUSIONS: In summary, we demonstrated the establishment of a feasible and reproducible 3D bioprocess using single-use STR for clinical-grade MSC,WJ production and provide evidence supporting comparability of 3D versus 2D production strategies. This comparability exercise evaluates the direct implementation of using single-use STR for the scale-up production of MSC,WJ and, by extension, other cell types intended for allogeneic therapies.

Expanding the phenotype of THRB: a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant.

Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders that often severely impair vision. Some patients manifest poor central vision as the first symptom due to cone-dysfunction, which is consistent with cone dystrophy (COD), Stargardt disease (STGD), or macular dystrophy (MD) among others. Here, we aimed to identify the genetic cause of autosomal dominant COD in one family. WGS was performed in 3 affected and 1 unaffected individual using the TruSeq Nano DNA library kit and the NovaSeq 6,000 platform (Illumina). Data analysis identified a novel spliceogenic variant (c.283 + 1G>A) in the thyroid hormone receptor beta gene (THRB) as the candidate disease-associated variant. Further genetic analysis revealed the presence of the same heterozygous variant segregating in two additional unrelated dominant pedigrees including 9 affected individuals with a diagnosis of COD (1), STGD (4), MD (3) and unclear phenotype (1). THRB has been previously reported as a causal gene for autosomal dominant and recessive thyroid hormone resistance syndrome beta (RTHß); however, none of the IRD patients exhibited RTHß. Genotype-phenotype correlations showed that RTHß can be caused by both truncating and missense variants, which are mainly located at the 3' (C-terminal/ligand-binding) region, which is common to both THRB isoforms (TRß1 and TRß2). In contrast, the c.283 + 1G>A variant is predicted to disrupt a splice site in the 5'-region of the gene that encodes the N-terminal domain of the TRß1 isoform protein, leaving the TRß2 isoform intact, which would explain the phenotypic variability observed between RTHß and IRD patients. Interestingly, although monochromacy or cone response alterations have already been described in a few RTHß patients, herein we report the first genetic association between a pathogenic variant in THRB and non-syndromic IRDs. We thereby expand the phenotype of THRB pathogenic variants including COD, STGD, or MD as the main clinical manifestation, which also reflects the extraordinary complexity of retinal functions mediated by the different THRB isoforms.

Hypopyon Uveitis as a Manifestation of Primary Choroidal Lymphoma.

A 78-year-old female was referred to our hospital due to a decrease of visual acuity in her left eye. On examination, presence of left choroidal folds and subretinal fluid was disclosed. After being misdiagnosed as neovascular age-related macular degeneration treatment with intravitreal injections of Aflibercept was started. Despite improvement of fluid, persistence of choroidal folds encouraged a magnetic resonance imaging revealing a left retrobulbar nodular lesion. Furthermore, development of hypopyon during follow-up allowed a flow cytometry analysis of an aqueous humour sample that confirmed infiltration by a non-Hodgkin mature B-cell lymphoproliferative process. Finally, treatment with Rituximab and intravenous corticosteroids achieved complete resolution. Primary choroidal lymphoma may occur with an atypical presentation, including hypopyon uveitis. Thus, familiarity with its clinical features is fundamental for an early recognition and correct management.

Differential analysis of the dentin soluble proteomic.

OBJECTIVES: To perform a differential analysis of the dentin soluble proteomic and assess the effects of tissue health state and protocol for protein extraction. We hypothesized the dentin soluble proteomic varies according to the tissue physiopathological state (intact vs. caries-affected) and protocol used to extract its proteins. METHODS: Dentin from freshly extracted non-carious and carious teeth were randomly assigned for protein extraction using either guanidine-HCl/ethylenediaminetetraacetic acid (EDTA) or acetic acid. Protein extracts from intact and caries-affected dentin were processed and digested with trypsin for shotgun label-free proteomic analysis (nLC-ESI-MS/MS). Peptides identification was performed on a nanoACQUITY UPLC-Xevo Q-Tof MS system. Peptides identified with scores of confidence greater than 95% were included in the quantitative statistical analysis embedded in the PLGS software. Differences between experimental conditions were calculated using Student test-t with significance pre-set at α=0.05. RESULTS: A total of 158 human proteins were identified. Approximately one-sixth of proteins (24/158) were present in at least two different extracts. Conversely, the greatest number of proteins (134/158) was identified uniquely in only one of the extracts. Overall, a larger number of soluble proteins was retrieved from caries-affected than intact dentin (86/158). Likewise, a greater number of proteins was extracted by the guanidine-HCl/EDTA (106/158) in comparison to acetic acid protocol. Several proteins detected in dentin extracts, mainly those from caries-affected teeth, are biological and/or metabolically involved with tissue turnover/remodeling. CONCLUSION: The identity/abundance of soluble proteins retrieved from and remained in dentin noticeably depend on this tissue physiopathological state and protocol used to remove its minerals. CLINICAL SIGNIFICANCE: The present findings brought new insight into the proteomic phenotype of human dentin and may provide targets for the development of novel caries disease-prevention therapies.

Effect of silver nanoparticles associated with fluoride on the progression of root dentin caries in vitro.

OBJECTIVES: To assess the anti-proteolytic effect and potential to inhibit dentin root caries progression of a silver nanoparticle and fluoride solution (CNanoF) in comparison to silver diamine fluoride (SDF). METHODS: 48 specimens of root dentin artificial caries lesion were treated with 38% SDF, CNanoF, CNano or F (n = 6 per group). Ph cycling with demineralization and remineralization solutions simulated caries lesion progression. In addition, specimens were incubated with or without bacterial collagenase in the remineralization solution to induce dentin proteolytic degradation. Dentin degradation was assessed by weight loss rate and hydroxyproline (Hyp) release. Changes in cross-sectional microhardness, and lesion permeability and collagen integrity as determined by confocal laser scanning microscopy indicated potential for further demineralization inhibition. The effect of the solutions on the activity of metalloproteinases (MMP) -2 and -9 was also investigated. Statistical analysis consisted of ANOVA, Kruskal-Wallis, and linear mixed models with post-hoc pairwise Tukey, Dunn, and t-tests (α = 0.05). RESULTS: Treatment with SDF resulted in lower weight loss rate than did other solutions, but all groups showed similar Hyp release (p = 0.183). SDF resulted in greater microhardness at superficial layers of the caries lesions (p<0.05), while there were no differences among CNanoF, CNano, and F. Lesion permeability was similar among all groups after pH cycling (p>0.05), with or without the use of collagenase (p = 0.58). No statistically significant difference was noted among solutions regarding collagen integrity after pH cycling; however, SDF-treated dentin had a significant decrease in collagen integrity when collagenase was used (p = 0.003). Interestingly, only SDF was able to completely inactivate MMP-2 and -9. CONCLUSIONS: CNanoF and SDF both potentially prevent dentin degradation during caries lesion progression in vitro; however, SDF was more effective at inhibiting further tissue demineralization.

Genetic profile in patients with complicated acute aortic syndrome: the GEN-AOR study.

INTRODUCTION AND OBJECTIVES: Genetic testing is becoming increasingly important for diagnosis and personalized treatments in aortopathies. Here, we aimed to genetically diagnose a group of acute aortic syndrome (AAS) patients consecutively admitted to an intensive care unit and to explore the clinical usefulness of AAS-associated variants during treatment decision-making and family traceability. METHODS: We applied targeted next-generation sequencing, covering 42 aortic diseases genes in AAS patients with no signs consistent with syndromic conditions. Detected variants were segregated by Sanger sequencing in available family members. Demographic features, risk factors and clinical symptoms were statistically analyzed by Fisher or Fisher-Freeman-Halton Exact tests, to assess their relationship with genetic results. RESULTS: Analysis of next-generation sequencing data in 73 AAS patients led to the detection of 34 heterozygous candidate variants in 14 different genes in 32 patients. Family screening was performed in 31 relatives belonging to 9 families. We found 13 relatives harboring the family variant, of which 10 showed a genotype compatible with the occurrence of AAS. Statistical tests revealed that the factors associated with a positive genetic diagnosis were the absence of hypertension, lower age, family history of AAS and absence of pain. CONCLUSIONS: Our findings broaden the spectrum of the genetic background for AAS. In addition, both index patients and studied relatives benefited from the results obtained, establishing the most appropriate level of surveillance for each group. Finally, this strategy could be reinforced by the use of stastistically significant clinical features as a predictive tool for the hereditary character of AAS. CLINICALTRIALS: gov (Identifier: NCT04751058).

Development of Proanthocyanidin-Loaded Mesoporous Silica Nanoparticles for Improving Dental Adhesion.

Dentin biomodification is a promising approach to enhance dental tissue biomechanics and biostability for restorative and reparative therapies. One of the most active dentin tissue biomodifiers is proanthocyanidin (PAC)-rich natural extracts, which are used in the dental bonding procedure in combination with resin-based adhesives (RBAs). This study aimed to investigate the use of mesoporous silica nanoparticles (MSNs) for the sustained delivery of PACs for dentin biomodification as a novel drug-delivery system for dental applications. The effects of the incorporation of MSN functionalized with 3-aminopropyltriethoxysilane (APTES) and loaded with PAC into an experimental RBA were assessed by characterizing the material mechanical properties. In addition, the immediate and long-term bonding performance of an experimental resin-based primer (RBP) containing MSN-APTES loaded with PAC was also evaluated. For that, different formulations of RBA and RBP were prepared containing 20% w/v MSN-APTES loaded with PAC before or after functionalization (MSN-PAC-APTES and MSN-APTES-PAC, respectively). The incorporation of MSN-APTES-PAC did not negatively impact the degree of conversion or the overall mechanical properties of the RBA. However, adding MSN-PAC-APTES resulted in inferior mechanical properties of the experimental RBA. In the adhesion studies, APTES-functionalized MSN was successfully added to an experimental RBP for drug-delivery purposes without compromising the bond strength to the dentin or the failure mode. Interestingly, the sequence of surface functionalization with APTES resulted in differences in the bonding performance, with better long-term results for RBP containing MSN loaded with PAC after functionalization.

¿Es necesaria la formación anual sobre reanimación cardiopulmonar en el colegio? / Is annual training on cardiopulmonary resuscitation necessary at school?

Objetivo: evaluar los conocimientos sobre reanimación cardiopulmonar (RCP) adquiridos en estudiantes de 5º de primaria de un colegio de Zaragoza (España) tras realizar un taller teórico-práctico y las diferencias en función de su repetición o no el año posterior.Método: ensayo controlado aleatorizado realizado entre 2019 y 2021. Se incluyó a 72 estudiantes matriculados que se asignaron aleatoriamente a dos grupos iguales. Un grupo recibió un taller teórico-práctico sobre RCP en dos sesiones de una hora, otro repitió la formación también el curso siguiente. Se midieron edad, sexo y conocimientos mediante test autoadministrado diseñado ad hoc (puntuación 0 a 13 máx.) antes y después del primer año y tras el segundo. Se realizaron índices de estadística descriptiva y contraste de hipótesis.Resultados: participaron 72 alumnos de 10,6 años de media. La puntuación se incrementó de manera estadísticamente significativa en ambos grupos (valor p< 0,001) el primer año. En el segundo año, la mediana de la puntuación total obtenida fue 11,0 (RIC= 2,0) en el grupo sin repetición y 13,0 (RIC= 1,0) en el que sí se repitió (p< 0,001). Este último grupo identificó mejor la comprobación inicial de consciencia, la actuación mientras llega ayuda, la actuación en inconsciencia sin respiración y la relación compresiones/ventilaciones (p< 0,05).Conclusión: la participación en el taller mejoró el conocimiento de los estudiantes. Quienes recibieron de nuevo la formación el año siguiente obtuvieron mayores conocimientos que aquellos que solo lo obtuvieron en una ocasión.(AU)

Objective: to evaluate the knowledge about cardiopulmonary resuscitation acquired by students in their 5th year of Primary School from a school in Zaragoza (Spain) after conducting a theoretical-practical workshop, and the differences based on whether it was repeated or not on the following year.Method: a controlled randomized study conducted between 2019 and 2021, which included 72 enrolled students who were randomly assigned to two equal arms. One of the arms attended a theoretical-practical workshop on cardiopulmonary resuscitation (CPR) in two one-hour sessions; the other arm also repeated the training the following year. Age, gender and knowledge were measured through a self-administered test which was designed ad hoc (scores from 0 to 13 maximum) before and after the first year and after the second year. Descriptive statistics indexes and hypothesis contrast were used.Results: the study included 72 students with 10.6 years as mean age. There was a statistically significant increase in scores in both arms (p value< 0.001) on the first year. On the second year, the median total score obtained was 11.0 (IQR= 2.0) in the arm without repetition and 13.0 (IQR= 1.0) in the arm with repetition (p< 0.001). This last arm presented better identification of the initial verification of consciousness, the action while waiting for help, the action in lack of consciousness without respiration, and the compression / ventilation ratio (p< 0.05).Conclusion: participation in the workshop improved the knowledge of students. Those who received training again on the following year obtained higher knowledge than those who only received it once.(AU)

Electrophysiological effects of adipose graft transposition procedure (AGTP) on the post-myocardial infarction scar: A multimodal characterization of arrhythmogenic substrate.

Objective: To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar. Background: Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed. Methods: MI was induced in 20 swine. Contrast-enhanced magnetic resonance (ce-MRI), electrophysiological study (EPS), and left-ventricular endocardial high-density mapping were performed 15 days post-MI. Animals were randomized 1:1 to AGTP or sham-surgery group and monitored with ECG-Holter. Repeat EPS, endocardial mapping, and ce-MRI were performed 30 days post-intervention. Myocardial SERCA2, Connexin-43 (Cx43), Ryanodine receptor-2 (RyR2), and cardiac troponin-I (cTnI) gene and protein expression were evaluated. Results: The AGTP group showed a significant reduction of the total infarct scar, border zone and dense scar mass by ce-MRI (p = 0.04), and a decreased total scar and border zone area in bipolar voltage mapping (p < 0.001). AGTP treatment significantly reduced the area of very-slow conduction velocity (<0.2 m/s) (p = 0.002), the number of deceleration zones (p = 0.029), and the area of fractionated electrograms (p = 0.005). No differences were detected in number of induced or spontaneous ventricular arrhythmias at EPS and Holter-monitoring. SERCA2, Cx43, and RyR2 gene expression were decreased in the infarct core of AGTP-treated animals (p = 0.021, p = 0.018, p = 0.051, respectively). Conclusion: AGTP is a safe reparative therapy in terms of arrhythmic risk and provides additional protective effect against adverse electrophysiological remodeling in ischemic heart disease.

Acellular cardiac scaffolds enriched with MSC-derived extracellular vesicles limit ventricular remodelling and exert local and systemic immunomodulation in a myocardial infarction porcine model.

Rationale: Extracellular vesicles (EVs) from mesenchymal stromal cell (MSC) are a potential therapy for cardiac healing after myocardial infarction (MI). Nevertheless, neither their efficient administration nor therapeutic mechanisms are fully elucidated. Here, we evaluate the preclinical efficacy of a tissue engineering approach to locally deliver porcine cardiac adipose tissue MSC-EV (cATMSC-EV) in an acute MI pig model. Methods: After MI by permanent ligation of the coronary artery, pigs (n = 24) were randomized to Untreated or treated groups with a decellularised pericardial scaffold filled with peptide hydrogel and cATMSC-EV purified by size exclusion chromatography (EV-Treated group) or buffer (Control group), placed over the post-infarcted myocardium. Results: After 30 days, cardiac MRI showed an improved cardiac function in EV-Treated animals, with significantly higher right ventricle ejection fraction (+20.8% in EV-Treated; p = 0.026), and less ventricle dilatation, indicating less myocardial remodelling. Scar size was reduced, with less fibrosis in the distal myocardium (-42.6% Col I in EV-Treated vs Untreated; p = 0.03), a 2-fold increase in vascular density (EV-Treated; p = 0.019) and less CCL2 transcription in the infarct core. EV-treated animals had less macrophage infiltration in the infarct core (-31.7% of CD163+ cells/field in EV-Treated; p = 0.026), but 5.8 times more expressing anti-inflammatory CD73 (p = 0.015). Systemically, locally delivered cATMSC-EV also triggered a systemic effect, doubling the circulating IL-1ra (p = 0.01), and reducing the PBMC rush 2d post-MI, the TNFα and GM-CSF levels at 30d post-MI, and modulating the CD73+ and CCR2+ monocyte populations, related to immunomodulation and fibrosis modulation. Conclusions: These results highlight the potential of cATMSC-EV in modulating hallmarks of ischemic injury for cardiac repair after MI.

Analyzing Psychotherapy on Twitter: An 11-Year Analysis of Tweets From Major U.S. Media Outlets.

Background: The Internet has become the main source of information on health issues, and information now determines the therapeutic preferences of patients. For this reason, it is relevant to analyze online information discussing psychotherapy. Objective: To investigate tweets posted by 25 major US media outlets between 2009 and 2019 concerning psychotherapy. Methods: We investigated tweets posted by 25 major US media outlets about psychotherapy between January 2009 and December 2019 as well as the likes generated. In addition, we measured the sentiment analysis of these tweets. Results: Most of the tweets analyzed focused on Mindfulness (5,498), while a low number were related to Psychoanalysis (376) and even less to Cognitive-Behavioral Therapy (61). Surprisingly, Computer-supported therapy, Psychodynamic therapy, Systemic therapy, Acceptance and commitment therapy, and Dialectical behavior therapy did not generate any tweet. In terms of content, efficacy was the main focus of the posted tweets, receiving Cognitive-Behavioral Therapy and Mindfulness a positive appraisal. Conclusions: US media outlets focused their interest on Mindfulness which may have contributed to the growing popularity in the past years of this therapeutic modality.