Proteome birthdating reveals age-selectivity of protein ubiquitination.

Within a cell, proteins have distinct and highly variable half-lives. As a result, the molecular ages of proteins can range from seconds to years. How the age of a protein influences its environmental interactions is a largely unexplored area of biology. To investigate the age-selectivity of cellular pathways, we developed a methodology termed "proteome birthdating" that barcodes proteins based on their time of synthesis. We demonstrate that this approach provides accurate measurements of protein turnover kinetics from a single biological sample encoding multiple labeling time-points. As a first application of the birthdated proteome, we investigated the age distribution of the human ubiquitinome. Our results indicate that the vast majority of ubiquitinated proteins in a cell consist of newly synthesized proteins and that these young proteins constitute the bulk of the degradative flux through the proteasome. Rapidly ubiquitinated nascent proteins are enriched in cytosolic subunits of large protein complexes. Conversely, proteins destined for the secretory pathway and vesicular transport have older ubiquitinated populations. Our data also identify a smaller subset of older ubiquitinated cellular proteins that do not appear to be targeted to the proteasome for rapid degradation. Together, our data provide an age census of the human ubiquitinome and establish proteome birthdating as a robust methodology for investigating the protein age-selectivity of diverse cellular pathways.

Mitochondrial permeability transition regulator, cyclophilin D, is transcriptionally activated by C/EBP during adipogenesis.

Age-related bone loss is associated with decreased bone formation, increased bone resorption, and accumulation of bone marrow fat. During aging, differentiation potential of bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) is shifted toward an adipogenic lineage and away from an osteogenic lineage. In aged bone tissue, we previously observed pathological opening of the mitochondrial permeability transition pore (MPTP) which leads to mitochondrial dysfunction, oxidative phosphorylation uncoupling, and cell death. Cyclophilin D (CypD) is a mitochondrial protein that facilitates opening of the MPTP. We found earlier that CypD is downregulated during osteogenesis of BMSCs leading to lower MPTP activity and, thus, protecting mitochondria from dysfunction. However, during adipogenesis, a fate alternative to osteogenesis, the regulation of mitochondrial function and CypD expression is still unclear. In this study, we observed that BMSCs have increased CypD expression and MPTP activity, activated glycolysis, and fragmented mitochondrial network during adipogenesis. Adipogenic C/EBPα acts as a transcriptional activator of expression of the CypD gene, Ppif, during this process. Inflammation-associated transcription factor NF-κB shows a synergistic effect with C/EBPα inducing Ppif expression. Overall, we demonstrated changes in mitochondrial morphology and function during adipogenesis. We also identified C/EBPα as a transcriptional activator of CypD. The synergistic activation of CypD by C/EBPα and the NF-κB p65 subunit during this process suggests a potential link between adipogenic signaling, inflammation, and MPTP gain-of-function, thus altering BMSC fate during aging.

Intrahepatic Biliary Colloid Carcinoma: A Rare Site for Recurrence.

A new biliary duct (BD) stricture raises questions about the presence of malignancy, especially with a history of metastatic pancreatic cancer. A few cases of colloid carcinoma (CC) of the pancreas have been published, but none have described recurrence in the biliary tract. We report a case of intrahepatic biliary CC that recurred after two years after the last dose of immunotherapy for pancreatic CC. In addition to a unique biliary cancer case presentation, this case raises awareness of the best strategy for cancer surveillance.

A Case of Zieve's Syndrome With the Development of Delirium Tremens.

A 50-year-old man presented to the emergency department with dark urine and altered mental status. Upon examination, the patient was found to be jaundiced with normal vitals. Laboratory investigation demonstrated macrocytic anemia and abnormal liver function tests. During his hospitalization, he developed delirium tremens in addition to the discovery of acute hemolytic anemia, hypercholesterolemia, and hypertriglyceridemia. Therefore, he was diagnosed with Zieve's syndrome (ZS), a rarely reported disease characterized by hemolytic anemia, cholestatic jaundice, and transient hyperlipidemia. Physicians encountering acute hemolytic anemia in a patient with concomitant acute liver injury should consider ZS as a differential diagnosis, as prompt recognition of the syndrome can help prevent unnecessary procedures and therapy.

A Multivariate Study for Determining the Relationship Between Physical Activity, Physical Fitness, and Academic Performance / Estudio multivariado para determinar la relación entre actividad física, condición física y rendimiento académico

The relationship between physical activity, physical fitness, and academic performance has been widely studied internationally. However, reports of this relationship are contradictory, and its impact is still a matter of controversy. For that reason, the current research determined the correlation between these three variables in a group of 56 female and 48 male Colombian students with an average age of 14.08 ± 0.89 years. A quantitative, correlational, and cross-sectional study was carried out. The physical activity was evaluated using PAQ-A questionnaire. For physical fitness, six tests from the Euro fitness battery were used. The academic performance in Spanish, Math, Natural, and Social Sciences were obtained from the grades for the participants at the end of the academic year. Correlations were determined by multivariate multiple linear regression. The obtained results suggest that aerobic endurance test had effect in the studied variables, whereas the correlation of the other tested predictors did not show any meaningful statistical result. In fact, academic performance is not affected by the physical fitness of the students at the time course grades were measured. (AU)

La relación entre la actividad física, la condición física y el rendimiento académico ha sido ampliamente estudiada a nivel internacional. Sin embargo, los reportes de esta relación son contradictorios y su impacto aún es motivo de controversia. Por ello, la presente investigación determinó la correlación entre estas tres variables en un grupo de estudiantes colombianos de los cuales 56 eran de género femenino y 48 masculino, con edad promedio de 14,08 ± 0,89 años. Se realizó un estudio cuantitativo, correlacional y transversal. La actividad física se evaluó mediante el cuestionario PAQ-A. Para la aptitud física, se utilizaron seis pruebas de la batería de test Eurofit. El rendimiento académico en Español, Matemáticas, Ciencias Naturales y Sociales se obtuvo a partir de las notas de los participantes al final del curso académico. Las correlaciones se determinaron mediante una regresión lineal múltiple multivariante. Los resultados obtenidos sugieren que la prueba de resistencia aeróbica tuvo efecto en las variables estudiadas, mientras que la correlación de los otros predictores probados no mostró ningún resultado estadístico significativo. De hecho, el rendimiento académico no es afectado por la condición física de los estudiantes durante el tiempo en el que fueron evaluados. (AU)

miRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling.

The ability to simultaneously modulate a set of genes for lineage-specific development has made miRNA an ideal master regulator for organogenesis. However, most miRNA deletions do not exhibit obvious phenotypic defects possibly due to functional redundancy. miRNAs are known to regulate skeletal lineages as the loss of their maturation enzyme Dicer impairs bone remodeling processes. Therefore, it is important to identify specific miRNA essential for bone homeostasis. We report the loss of MIR27a causing severe osteoporosis in mice. MIR27a affects osteoclast-mediated bone resorption but not osteoblast-mediated bone formation during skeletal remodeling. Gene profiling and bioinformatics further identify the specific targets of MIR27a in osteoclast cells. MIR27a exerts its effects on osteoclast differentiation through modulation of Squstm1/p62 whose mutations have been linked to Paget's disease of bone. Our findings reveal a new MIR27a-p62 axis necessary and sufficient to mediate osteoclast differentiation and highlight a therapeutic implication for osteoporosis.

Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation.

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial, and its role in patients with S. aureus osteomyelitis is unknown. To address this knowledge gap, we completed a clinical study and observed elevated serum IL-27 levels (20-fold higher, P < 0.05) in patients compared with healthy controls. Remarkably, IL-27 serum levels were 60-fold higher in patients immediately following septic death than in uninfected patients (P < 0.05), suggesting a pathogenic role of IL-27. To test this hypothesis, we evaluated S. aureus osteomyelitis in WT and IL-27Rα-/- mice with and without exogenous IL-27 induction by intramuscular injection of rAAV-IL-27p28 or rAAV-GFP, respectively. We found that IL-27 was induced at the surgical site within 1 day of S. aureus infection of bone and was expressed by M0, M1 and M2 macrophages and osteoblasts but not by osteoclasts. Unexpectedly, exogenous IL-27p28 (~2 ng·mL-1 in serum) delivery ameliorated soft tissue abscesses and peri-implant bone loss during infection, accompanied by enhanced local IL-27 expression, significant accumulation of RORγt+ neutrophils at the infection site, a decrease in RANK+ cells, and compromised osteoclast formation. These effects were not observed in IL-27Rα-/- mice compared with WT mice, suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during infection. In vitro studies and bulk RNA-seq of infected tibiae showed that IL-27 increased nos1, nos2, il17a, il17f, and rorc expression but did not directly stimulate chemotaxis. Collectively, these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following S. aureus infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis.

Optimization of contrast material administration for coronary CT angiography using a software-based test-bolus evaluation algorithm.

OBJECTIVES: To evaluate the benefit of a prototype circulation time-based test bolus evaluation algorithm for the individualized optimal timing of contrast media (CM) delivery in patients undergoing coronary CT angiography (CCTA). METHODS: Thirty-two patients (62 ± 16 years) underwent CCTA using a prototype bolus evaluation tool to determine the optimal time-delay for CM administration. Contrast attenuation, signal-to-noise ratio (SNR), objective, and subjective image quality were evaluated by two independent radiologists. Results were compared to a control cohort (matched for age, sex, body mass index, and tube voltage) of patients who underwent CCTA using the generic test bolus peak attenuation +4 s protocol as scan delay. RESULTS: In the study group, the mean time delay to CCTA acquisition was significantly longer (26.0 ± 2.9 s) compared to the control group (23.1 ± 3.5 s; p < 0.01). In the study group, SNR improvement was seen in the right coronary artery (17.5 vs 13; p = 0.028), the left main (15.3 vs 12.3; p = 0.027), and the left anterior descending artery (18.5 vs 14.1; p = 0.048). Subjective image quality was rated higher in the study group (4.75 ± 0.7 vs 3.64 ± 0.5; p < 0.001). CONCLUSIONS: The prototype test bolus evaluation algorithm provided a reliable patient-specific scan delay for CCTA that ensured homogenous vascular attenuation, improvement in objective and subjective image quality, and avoidance of beam hardening artifacts. ADVANCES IN KNOWLEDGE: The prototype contrast bolus evaluation and optimization tool estimated circulation time-based time-delay improves the overall quality of CCTA.

Performance of an Artificial Intelligence-Based Platform Against Clinical Radiology Reports for the Evaluation of Noncontrast Chest CT.

RATIONALE AND OBJECTIVES: Research on implementation of artificial intelligence (AI) in radiology workflows and its impact on reports remains scarce. In this study, we aim to assess if an AI platform would perform better than clinical radiology reports in evaluating noncontrast chest computed tomography (CT) scans. MATERIALS AND METHODS: Consecutive patients who had undergone noncontrast chest CT were retrospectively identified. The radiology reports were reviewed in a binary fashion for reporting of pulmonary lesions, pulmonary emphysema, aortic dilatation, coronary artery calcifications (CAC), and vertebral compression fractures (VCF). CT scans were then processed using an AI platform. The reports' findings and the AI results were subsequently compared to a consensus read by two board-certificated radiologists as reference. RESULTS: A total of 100 patients (mean age: 64.2 ± 14.8 years; 57% males) were included in this study. Aortic segmentation and calcium quantification failed to be processed by AI in 2 and 3 cases, respectively. AI showed superior diagnostic performance in identifying aortic dilatation (AI: sensitivity: 96.3%, specificity: 81.4%, AUC: 0.89) vs (Reports: sensitivity: 25.9%, specificity: 100%, AUC: 0.63), p <0.001; and CAC (AI: sensitivity: 89.8%, specificity: 100, AUC: 0.95) vs (Reports: sensitivity: 75.4%, specificity: 94.9%, AUC: 0.85), p = 0.005. Reports had better performance than AI in identifying pulmonary lesions (Reports: sensitivity: 97.6%, specificity: 100%, AUC: 0.99) vs (AI: sensitivity: 92.8%, specificity: 82.4%, AUC: 0.88), p = 0.024; and VCF (Reports: sensitivity:100%, specificity: 100%, AUC: 1.0) vs (AI: sensitivity: 100%, specificity: 63.7%, AUC: 0.82), p <0.001. A comparable diagnostic performance was noted in identifying pulmonary emphysema on AI (sensitivity: 80.6%, specificity: 66.7%. AUC: 0.74) and reports (sensitivity: 74.2%, specificity: 97.1%, AUC: 0.86), p = 0.064. CONCLUSION: Our results demonstrate that incorporating AI support platforms into radiology workflows can provide significant added value to clinical radiology reporting.

Occurrence and molecular characterization of cyst nematode species (Globodera spp.) associated with potato crops in Colombia.

Potato cyst nematodes (PCN) from the genus Globodera spp. cause major losses in the potato (Solanum tuberosum) industry worldwide. Despite their importance, at present little is known about the status of this plant pathogen in cultivated potatoes in Colombia. In this study, a total of 589 samples collected from 75 geographic localities in nine potato producing regions of Colombia (Cundinamarca, Boyacá, Antioquia, Nariño, Santander, Norte de Santander, Tolima, Caldas and Cauca) were assayed for the presence of potato cyst nematodes. Fifty-seven percent of samples tested positive for PCN. Based on phylogenetic analysis of the internal transcribed spacer region (ITS1-5.8S-ITS2) of the rRNA gene and D2-D3 expansion segments of the 28S rRNA gene, all populations but one were identified as Globodera pallida. Sequences of G. pallida from Colombia formed a monophyletic group closely related to Peruvian populations, with the lowest average number of nucleotide substitutions per site (Dxy = 0.002) and net nucleotide substitutions per site (Da = 0.001), when compared to G. pallida populations from Europe, South and North America. A single sample formed a well-supported subclade along with G. rostochiensis and G. tabacum from Japan, USA and Argentina. To our knowledge this is the first comprehensive survey of Globodera populations from Colombia that includes genetic data. Our findings on species diversity and phylogenetic relationships of Globodera populations from Colombia may help elucidate the status and distribution of Globodera species, and lead to the development of accurate management strategies for the potato cyst nematodes.

The Impact of driver distraction and secondary tasks with and without other co-occurring driving behaviors on the level of road traffic crashes.

Driving safety is typically affected by concurrent non-driving tasks. These activities might negatively impact the trips' outcome and cause near-crash or crash incidents and accidents. The crashes impose a tremendous social and economic cost to society and might affect the involving individuals' quality of life. As it stands, road injuries are ranked among top-ten leading causes of death by the World Health Organization. Distracted driving is defined as an attention diversion of the driver toward a competing activity. It was shown in numerous studies that distracted driving increase the probability of near-crash or crash events. By leveraging the statistical power of the large SHRP2 naturalistic data, we are able to quantify the preponderance of specific distractions during daily trips and confirm the causality factor of an ubiquitous non-driving task in the crash event. We show that, except for phone usage which happens more frequently in near-crash and crash categories than in baseline trips, both distracted driving and secondary tasks occur almost uniformly in different types of trips. In this study, we investigate the impact of the co-occurrence of distracted driving with other driving behaviors and secondary tasks. It is found that the co-occurrence of distracted driving with other driving behaviors or secondary tasks increase the chance of near-crash and crash events. This study's findings can inform the design and development of more precise and reliable driving assistance and warning systems.

Brief Research Report: Prehospital Rapid Sequence Airway.

BACKGROUND: Rapid Sequence Airway (RSA) describes the administration of an induction agent and paralytic followed by the intended primary placement of an extraglottic airway device rather than an endotracheal tube. The purpose of this study was to determine the success rates for prehospital RSA. The secondary goal was to determine aspiration rates among patients managed with RSA. METHODS: Adult and pediatric prehospital RSA cases between 2005 and 2017 reported to an airway quality assurance registry from one ground and one air agency were reviewed. Success was defined as the ability to adequately ventilate patients after extraglottic device placement. Aspiration was defined as radiologic evidence (chest x-ray or CT scan) within 48 hours of hospital presentation. RESULTS: 68 patients underwent RSA with a King LTS-D (n = 24), LMA-Supreme (n = 28), Combitube (n = 2), LMA-Unique (n = 8) and iGel (n = 6). Age ranged from 1 year to 73 years with 10 patients less than 18. RSA was successful in 64 (94%) cases; 56 (88%) were successful on first pass and 63 (98%) within 2 attempts. The RSA procedure occurred in an aircraft in 14 (21%) of cases and 71% of patients were in cervical precautions. Duration of EGD insertion prior to hospital arrival ranged from 5 to 102 minutes with an average of 34.5 minutes. Aspiration data was available for 46 patients of whom 4 (8.7%) were found to have evidence of aspiration. CONCLUSION: Overall and first pass RSA success rates were high and aspiration rates were low in this quality assurance registry despite predictors of airway difficulty. RSA may be a reasonable alternative to RSI for prehospital airway management that merits further research.

Deterioration estimation for predicting and controlling RUL of a friction drive system.

This paper develops a method for estimating the state of deterioration of a friction drive system and presents its use for predicting and controlling the Remaining Useful Life (RUL) of such a system. The friction drive system is assumed to be affected by endogenous uncertainties and exogenous disturbances. The proposed method is intended for on-line estimation of the contact surface deterioration and it is based on a parameter-varying model that includes both the motion dynamics and the deterioration dynamics of the device. Since, in the presented setting, the control actions on the mechanical system play a role on the non-linear deterioration dynamics, an Extended Kalman Filter is developed for simultaneously estimating both the state of deterioration and its associated estimation error bounds. A numerical example is presented to illustrate the interest of such estimations for RUL prognosis and RUL control. The presented example considers the availability of angular speed measurements and the possibility of re-planning motor torques and/or re-planning desired angular speeds in order to control RUL based on RUL prognosis.

Effects of mesenchymal stromal cell-conditioned media on measures of lung structure and function: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Lung disease is a leading cause of morbidity and mortality. A breach in the lung alveolar-epithelial barrier and impairment in lung function are hallmarks of acute and chronic pulmonary illness. This review is part two of our previous work. In part 1, we demonstrated that CdM is as effective as MSCs in modulating inflammation. Herein, we investigated the effects of mesenchymal stromal cell (MSC)-conditioned media (CdM) on (i) lung architecture/function in animal models mimicking human lung disease, and (ii) performed a head-to-head comparison of CdM to MSCs. METHODS: Adhering to the animal Systematic Review Centre for Laboratory animal Experimentation protocol, we conducted a search of English articles in five medical databases. Two independent investigators collected information regarding lung: alveolarization, vasculogenesis, permeability, histologic injury, compliance, and measures of right ventricular hypertrophy and right pulmonary pressure. Meta-analysis was performed to generate random effect size using standardized mean difference with 95% confidence interval. RESULTS: A total of 29 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. CdM improved all measures of lung structure and function. Moreover, no statistical difference was observed in any of the lung measures between MSCs and CdM. CONCLUSIONS: In this meta-analysis of animal models recapitulating human lung disease, CdM improved lung structure and function and had an effect size comparable to MSCs.

Multisystem inflammatory syndrome in children: A systematic review.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (COVID-19). We aimed to describe the typical presentation and outcomes of children diagnosed with this hyperinflammatory condition. METHODS: We conducted a systematic review to communicate the clinical signs and symptoms, laboratory findings, imaging results, and outcomes of individuals with MIS-C. We searched four medical databases to encompass studies characterizing MIS-C from January 1st, 2020 to July 25th, 2020. Two independent authors screened articles, extracted data, and assessed risk of bias. This review was registered with PROSPERO CRD42020191515. FINDINGS: Our search yielded 39 observational studies (n = 662 patients). While 71·0% of children (n = 470) were admitted to the intensive care unit, only 11 deaths (1·7%) were reported. Average length of hospital stay was 7·9 ± 0·6 days. Fever (100%, n = 662), abdominal pain or diarrhea (73·7%, n = 488), and vomiting (68·3%, n = 452) were the most common clinical presentation. Serum inflammatory, coagulative, and cardiac markers were considerably abnormal. Mechanical ventilation and extracorporeal membrane oxygenation were necessary in 22·2% (n = 147) and 4·4% (n = 29) of patients, respectively. An abnormal echocardiograph was observed in 314 of 581 individuals (54·0%) with depressed ejection fraction (45·1%, n = 262 of 581) comprising the most common aberrancy. INTERPRETATION: Multisystem inflammatory syndrome is a new pediatric disease associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is dangerous and potentially lethal. With prompt recognition and medical attention, most children will survive but the long-term outcomes from this condition are presently unknown. FUNDING: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.

Amplified Flow Imaging (aFlow): A Novel MRI-Based Tool to Unravel the Coupled Dynamics Between the Human Brain and Cerebrovasculature.

With each heartbeat, periodic variations in arterial blood pressure are transmitted along the vasculature, resulting in localized deformations of the arterial wall and its surrounding tissue. Quantification of such motions may help understand various cerebrovascular conditions, yet it has proven technically challenging thus far. We introduce a new image processing algorithm called amplified Flow (aFlow) which allows to study the coupled brain-blood flow motion by combining the amplification of cine and 4D flow MRI. By incorporating a modal analysis technique known as dynamic mode decomposition into the algorithm, aFlow is able to capture the characteristics of transient events present in the brain and arterial wall deformation. Validating aFlow, we tested it on phantom simulations mimicking arterial walls motion and observed that aFlow displays almost twice higher SNR than its predecessor amplified MRI (aMRI). We then applied aFlow to 4D flow and cine MRI datasets of 5 healthy subjects, finding high correlations between blood flow velocity and tissue deformation in selected brain regions, with correlation values r = 0.61 , 0.59, 0.52 for the pons, frontal and occipital lobe ( ). Finally, we explored the potential diagnostic applicability of aFlow by studying intracranial aneurysm dynamics, which seems to be indicative of rupture risk. In two patients, aFlow successfully visualized the imperceptible aneurysm wall motion, additionally quantifying the increase in the high frequency wall displacement after a one-year follow-up period (20%, 76%). These preliminary data suggest that aFlow may provide a novel imaging biomarker for the assessment of aneurysms evolution, with important potential diagnostic implications.

Habilidades gnósico-práxicas relacionadas con dificultades del aprendizaje de la lectura y la escritura en individuos de 9 a 12 años / Gnosis-praxic Skills Related to Disabilities in Learning to Read and Write in Individuals Aged 9 to 12 Years

Resumen Las dificultades del aprendizaje constituyen una de las principales causas de fracaso escolar; su aparición temprana puede evidenciarse en las habilidades gnósico-práxicas que soportan los procesos de lectura y escritura. Objetivo: Describir las habilidades gnósicas y práxicas en niños escolares, de 9 a 12 años de edad, asociadas a la presencia o no de dificultades en la lectura y/o la escritura. Participantes: 53 niños de una institución pública del municipio de Sabaneta-Colombia, divididos en dos grupos, uno compuesto por 16 niños con dificultades en la lectura y/o escritura y, el otro, por 37 niños sin dificultades en estos procesos. Resultados: La comparación intergrupos evidenció diferencias estadísticas (valor p y tamaño del efecto) significativas en aspectos cruciales para el proceso de lectura y escritura: la formación de imágenes visoconstruccionales y la velocidad, la planeación y la coordinación motora, evaluadas a partir de las tareas gnósico-práxicas de Sucesión de números y letras (WISC-IV) y Tapping (BANETA). Adicionalmente, se hallaron diferencias estadísticas en las subpruebas de Esterognosia, y correlaciones significativas entre Tapping y la velocidad al escribir palabras (BANETA). Conclusión: Las habilidades gnósico-práxicas no son plenamente los procesos predominantes en las diferencias intergrupos, si bien las habilidades motoras se vinculan con los procesos de aprendizaje y las dificultades que en ellos puedan presentarse, como lo sugieren las correlaciones dadas entre la subprueba de velocidad motora y el proceso de escritura. Adicionalmente, la velocidad de procesamiento y la memoria operativa se presentan como procesos transversales a las habilidades gnósico-práxicas y de lectura y escritura.

Abstract Learning disabilities constitute one of the main causes of school failure; their early manifestation may be evidenced in the gnosis-praxis skills that support reading and writing processes. Objective: To describe the performance of gnosis-praxis skills in school children (aged from 9 to 12 years old), associated to the existence or not of reading and/or writing difficulties. Participants: 53 children of a public school in Sabaneta - Colombia, divided into two groups, one consisting of 16 children with difficulties in reading and/or writing and, the other, by 37 children without difficulties in these processes. Results: The intergroup comparison showed significant statistical differences , in crucial aspects for reading and writing process: the visoconstructional image formation, speed, planning and motor coordination, obtained from the gnosis - praxis tasks of Letter-Number Sequencing (WISC-IV) and Tapping (BANETA). Additionally, statistical differences were found in the subtests of Stereognosis (BANETA) and significant correlations between Tapping and the speed rate in writing words. Conclusion: Gnosis - praxis skills are not the predominant processes in intergroup differences, even though motor skills are linked to learning process and the difficulties they may arise, as suggested by the correlations given between the motor speed subtest and the writing process. In addition, processing speed and operational memory are shown as crosscutting processes in gnosis-praxis, reading and writing skills.

Safety and efficacy of cell therapies in pediatric heart disease: a systematic review and meta-analysis.

BACKGROUND: Adult clinical trials have reported safety and the therapeutic potential of stem cells for cardiac disease. These observations have now translated to the pediatric arena. We conducted a meta-analysis to assess safety and efficacy of cell-based therapies in animal and human studies of pediatric heart disease. METHODS AND RESULTS: A literature search was conducted to examine the effects of cell-based therapies on: (i) safety and (ii) cardiac function. In total, 18 pre-clinical and 13 human studies were included. Pre-clinical: right ventricular dysfunction was the most common animal model (80%). Cardiac-derived (28%) and umbilical cord blood (24%) cells were delivered intravenously (36%) or intramyocardially (35%). Mortality was similar between cell-based and control groups (OR 0.94; 95% CI 0.05, 17.41). Cell-based treatments preserved ejection fraction by 6.9% (p < 0.01), while intramyocardial at a dose of 1-10 M cells/kg optimized ejection fraction. Clinical: single ventricle physiology was the most common cardiac disease (n = 9). Cardiac tissue was a frequent cell source, dosed from 3.0 × 105 to 2.4 × 107 cells/kg. A decrease in adverse events occurred in the cell-based cohort (OR 0.17, p < 0.01). Administration of cell-based therapies improved ejection fraction (MD 4.84; 95% CI 1.62, 8.07; p < 0.01). CONCLUSIONS: In this meta-analysis, cell-based therapies were safe and improved specific measures of cardiac function. Implications from this review may provide methodologic recommendations (source, dose, route, timing) for future clinical trials. Of note, many of the results described in this study pattern those seen in adult stem cell reviews and meta-analyses.