Formoxyboranes as hydroborane surrogates for the catalytic reduction of carbonyls through transfer hydroboration.

A new class of Lewis base stabilized formoxyboranes demonstrates the feasibility of catalytic transfer hydroboration. In the presence of a ruthenium catalyst, they have shown broad applicability for reducing carbonyl compounds. Various borylated alcohols are obtained in high selectivity and yields up to 99%, tolerating several functional groups. Computational studies enabled to propose a mechanism for this transformation, revealing the role of the ruthenium catalyst and the absence of hydroborane intermediates.

Biooxidation of hydrogen sulfide to sulfur by moderate thermophilic acidophilic bacteria.

The copper industry utilizes significant amounts of sulfuric acid in its processes, generating sulfate as waste. While sulfate-reducing bacteria can remove sulfate, it produces hydrogen sulfide (H2S) as a byproduct. This study examined the capability of a consortium consisting of Sulfobacillus thermosulfidooxidans and Sulfobacillus acidophilus to partially oxidize H2S to S° at a temperature of 45 °C. A fixed-bed bioreactor, with glass rings as support material and sodium thiosulfate as a model electron donor, was inoculated with the consortium. Formation of biofilms was crucial to maintain the bioreactor's steady state, despite high flow rates. Afterward, the electron donor was changed to H2S. When the bioreactor was operated continuously and with high aeration, H2S was fully oxidized to SO42-. However, under conditions of low aeration and at a concentration of 0.26 g/L of H2S, the consortium was able to oxidize H2S to S° with a 13% yield. S° was discovered attached to the glass rings and jarosite. The results indicate that the consortium could oxidize H2S to S° with a 13% yield under low aeration and at a concentration of 0.26 g/L of H2S. The findings highlight the capability of a Sulfobacillus consortium to convert H2S into S°, providing a potential solution for addressing environmental and safety issues associated with sulfate waste generated by the mining industry.

Diseño de un modelo de ronda de seguridad para unidades de cuidados intensivos / Design of a safety round model for intensive care units

Introducción: Las rondas de seguridad (RS) son una herramienta operativa que permite conocer la adherencia a las buenas prácticas, ayuda a identificar riesgos e incidentes en seguridad del paciente (SP), permitiendo implementar acciones de mejora. El objetivo de este trabajo fue el diseño de un procedimiento para realizar RS en una unidad de cuidados intensivos (UCI). Métodos: Elaboración de un listado de verificación para el desarrollo de RS en una UCI mediante técnica de grupo nominal, con la participación de directivos, mandos intermedios y profesionales de diferentes disciplinas y categorías. En primer lugar, un grupo de expertos consensuó, atendiendo a las recomendaciones en buenas prácticas en SP, la definición de ítems, su codificación, los criterios de cumplimiento y el impacto de su incumplimiento. Posteriormente, determinó su viabilidad mediante un estudio transversal a través del pilotaje de 2 RS para ajustar los ítems en condiciones de práctica clínica real. Resultados: Se ha obtenido un modelo de RS específico para UCI mediante un listado de verificación. El grupo de expertos elaboró un primer listado compuesto por 39 ítems de 6 dimensiones esenciales y definió el modo de realización. El tiempo medio de realización de las 2 RS fue de 85minutos, incluyendo el briefing y debriefing posterior. Tras el pilotaje de validación se redujo las dimensiones a 5, se suprimió 3 ítems, se trasladó 2 ítems a otra dimensión y se modificó 3 ítems relativos a infecciones nosocomiales y consentimiento informado. Además, se redefinieron las fuentes de datos, los criterios de cumplimiento y su peso relativo. El listado definitivo fue considerado útil y relevante para mejorar la práctica. Conclusiones: Mediante una metodología de consenso se ha construido un listado de verificación para ser usado en las RS de una UCI. Este modelo puede servir de base para su empleo en servicios asistenciales de similares características.(AU)

Introduction: Safety Rounds (SR) are an operational tool that allow knowing adherence to good practices, help identify risks and incidents in patient safety (PS), allowing improvement actions to be implemented. The objective of this work was the design of a procedure to perform SR in an Intensive Care Unit (ICU). Methods: Preparation of a checklist for the development of SR in the ICU through the nominal group technique, with the participation of managers, middle managers and professionals from different disciplines and categories. In the first place, a group of experts agreed, based on the recommendations on good practices in PS, the definition of items, their coding, the criteria for compliance and the impact of non-compliance. Subsequently, its viability was determined through a cross-sectional study through the piloting of two SRs to adjust the items in real clinical practice conditions. Results: A specific SR model for ICUs has been obtained through a checklist. The group of experts prepared a first list made up of 39 items of 6 essential dimensions and defined the method of implementation. Mean time to complete the two SRs was 85minutes, including the briefing and subsequent debriefing. After the validation pilot, the dimensions were reduced to 5, 3 items were deleted, 2 items were transferred to another dimension and 3 items related to nosocomial infections and informed consent were modified. In addition, the data sources, the compliance criteria and their relative weight were redefined. The final list was considered useful and relevant to improve practice. Conclusions: Through a consensus methodology, a checklist has been built to be used in the RS of an ICU. This model can serve as a basis for its use in healthcare services with similar characteristics.(AU)

Volatilome Analysis of Soursop Fruits for the Determination of Kairomone Components That Attract the Annonaceae Fruit Weevil (Optatus palmaris Pascoe).

Soursop possesses the largest fruit size of the Annona genus. However, this species is threatened by the Annonaceae fruit weevil (Optatus palmaris), which can cause the destruction of whole soursop fruits. Recently, the potential of semiochemicals for the management of this insect is highlighted, and its aggregation pheromone has been elucidated. This pheromone works well only when mixed with soursop volatiles. Thus, the aim of this research was to determine specific kairomone components to potentiate the aggregation pheromone of this Annonaceae fruit weevil. This task was carried out via volatilome analysis of soursop fruits, which was correlated with the biological activity of the identified volatiles. The GC-MS analysis of aroma collections of mature soursop fruits and flowers, determined using multivariate data analysis, confirmed a volatile differentiation between these organs. The volatile variation between fruits and flowers was reflected in weevils' preference for mature fruits instead of flowers. Moreover, weevils' response to soursop fruits increased with more mature fruits. This was correlated with volatile changes throughout the phenological stages of soursop fruits. The two volatiles most correlated with weevils' attraction were benzothiazole and (E)-ß-caryophyllene. These volatiles only evoked a response when mixed and potentiated the attraction of the aggregation pheromone. Thus, these two volatiles are active kairomone components with the potential for being used in combination with the aggregation pheromone of Annonaceae fruit weevils in field trials.

Dysphagia in patients undergoing esophageal atresia surgery: Assessment using a functional scale. / Disfagia en pacientes intervenidos de atresia de esófago: valoración con una escala funcional.

INTRODUCTION: Dysphagia is defined as difficulty swallowing. Up to 84% of patients undergoing esophageal atresia surgery have dysphagia beyond the neonatal period. MATERIALS AND METHODS: A retrospective study of patients undergoing esophageal atresia surgery from 2005 to 2021 was carried out. The Functional Oral Intake Scale (FOIS) was used to assess dysphagia in 4 age groups (< 1 year old, 1-4 years old, 5-11 years old, and > 11 years old). FOIS scores < 7 or symptoms of choking, impaction, or food aversion were regarded as dysphagia. RESULTS: 63 patients were analyzed. 74% (47/63) had dysphagia during follow-up. Prevalence was 50% in patients < 1 year old (FOIS mean 4.32), 77% in patients aged 1-4 (FOIS mean 5.61), 45% in patients aged 5-11 (FOIS mean 5.87), and 38% in patients > 11 years old (FOIS mean 6.8). The most frequent causes of dysphagia were stenosis, which occurred in 38% of the patients (n=24), and gastroesophageal reflux (n=18), which was present in 28% of the patients. Both conditions were associated with significantly lower mean FOIS scores (p< 0.05) in the patients under 11 years of age. Differences (p< 0.05) were found in the dysphagia-associated perinatal factors in the various age groups, with longer ventilation assistance times, parenteral nutrition, and hospital stays. CONCLUSIONS: Dysphagia is an extremely frequent symptom at any given age in patients undergoing esophageal atresia surgery. A standardized, cross-disciplinary follow-up is key to improve quality of life.

INTRODUCCION: La disfagia se define como dificultad en el proceso de alimentación. Hasta un 84% de pacientes intervenidos de atresia de esófago tienen disfagia más allá del periodo neonatal. MATERIAL Y METODOS: Estudio retrospectivo de serie de casos intervenidos por atresia de esófago 2005-2021. Se utilizó la escala FOIS (Functional Oral Intake Scale) para cuantificar la disfagia en 4 grupos de edad (menores de 1 año, 1-4 años, 5-11 años y mayores de 11 años). Se consideró disfagia cualquier valor de FOIS < 7 o síntomas de atragantamiento, impactación o aversión alimentaria. RESULTADOS: Se obtuvieron datos de 63 pacientes. El 74% (47/63) presentó disfagia durante el seguimiento. La prevalencia fue del 50% < 1 año (media FOIS 4.32), 77% 1-4 años (media FOIS 5.61), 45% 5-11 años (media FOIS 5.87) y 38% > 11 años (media FOIS 6.8). Las causas más frecuentes de disfagia fueron la estenosis, que presentó un 38% de los pacientes (n= 24) y el reflujo gastroesofágico (n= 18), que presentó a su vez un 28% de los pacientes. Ambas condiciones se asociaron con unos valores medios de FOIS significativamente menores (p< 0,05) en los pacientes menores de 11 años. Se encontraron diferencias (p< 0,05) en factores perinatales asociados a disfagia en los distintos periodos de edad, a destacar mayor tiempo medio de: asistencia ventilatoria, nutrición parenteral e ingreso hospitalario. CONCLUSIONES: La disfagia es un síntoma extremadamente frecuente a cualquier edad en los pacientes intervenidos de atresia de esófago. Un seguimiento estandarizado y multidisciplinar es esencial para mejorar la calidad de vida de estos pacientes.

Disfagia en pacientes intervenidos de atresia de esófago: valoración con una escala funcional / Dysphagia in patients undergoing esophageal atresia surgery: Assessment using a functional scale

Introducción: La disfagia se define como dificultad en el procesode alimentación. Hasta un 84% de pacientes intervenidos de atresia deesófago tienen disfagia más allá del periodo neonatal.Material y métodos: Estudio retrospectivo de serie de casos intervenidos por atresia de esófago 2005-2021. Se utilizó la escala FOIS(Functional Oral Intake Scale) para cuantificar la disfagia en 4 gruposde edad (menores de 1 año, 1-4 años, 5-11 años y mayores de 11 años).Se consideró disfagia cualquier valor de FOIS < 7 o síntomas de atragantamiento, impactación o aversión alimentaria.Resultados: Se obtuvieron datos de 63 pacientes. El 74% (47/63)presentó disfagia durante el seguimiento. La prevalencia fue del 50%< 1 año (media FOIS 4.32), 77% 1-4 años (media FOIS 5.61), 45% 5-11años (media FOIS 5.87) y 38% > 11 años (media FOIS 6.8). Las causasmás frecuentes de disfagia fueron la estenosis, que presentó un 38% delos pacientes (n= 24) y el reflujo gastroesofágico (n= 18), que presentóa su vez un 28% de los pacientes. Ambas condiciones se asociaron conunos valores medios de FOIS significativamente menores (p< 0,05) enlos pacientes menores de 11 años. Se encontraron diferencias (p< 0,05)en factores perinatales asociados a disfagia en los distintos periodosde edad, a destacar mayor tiempo medio de: asistencia ventilatoria,nutrición parenteral e ingreso hospitalario. Conclusiones: La disfagia es un síntoma extremadamente frecuentea cualquier edad en los pacientes intervenidos de atresia de esófago. Unseguimiento estandarizado y multidisciplinar es esencial para mejorarla calidad de vida de estos pacientes(AU)

Introduction: Dysphagia is defined as difficulty swallowing. Up to84% of patients undergoing esophageal atresia surgery have dysphagiabeyond the neonatal period. Materials and methods: A retrospective study of patients undergoing esophageal atresia surgery from 2005 to 2021 was carried out. TheFunctional Oral Intake Scale (FOIS) was used to assess dysphagia in 4age groups (< 1 year old, 1-4 years old, 5-11 years old, and 11 years old). FOIS scores < 7 or symptoms of choking, impaction, or food aversionwere regarded as dysphagia. Results: 63 patients were analyzed. 74% (47/63) had dysphagiaduring follow-up. Prevalence was 50% in patients < 1 year old (FOISmean 4.32), 77% in patients aged 1-4 (FOIS mean 5.61), 45% in patientsaged 5-11 (FOIS mean 5.87), and 38% in patients > 11 years old (FOISmean 6.8). The most frequent causes of dysphagia were stenosis, whichoccurred in 38% of the patients (n=24), and gastroesophageal reflux(n=18), which was present in 28% of the patients. Both conditions wereassociated with significantly lower mean FOIS scores (p< 0.05) in thepatients under 11 years of age. Differences (p< 0.05) were found in thedysphagia-associated perinatal factors in the various age groups, withlonger ventilation assistance times, parenteral nutrition, and hospital stays. Conclusions: Dysphagia is an extremely frequent symptom at anygiven age in patients undergoing esophageal atresia surgery. A standardized, cross-disciplinary follow-up is key to improve quality of life.(AU)

Immersive virtual plus-maze to examine behavior and psychophysiological-related variables in young people with problematic alcohol and cannabis consumption.

Stressful events appear to be risky situations that can precipitate the consumption of drugs. One way to recreate stressful contexts, in an ecological and controlled method, is through immersive virtual reality (VR). In our study, we designed the scenario of an elevated plus-maze (EPM) using VR, which is widely used in animal models to assess unconditioned anxiety. This task allowed us to analyze the behavioral, psychophysiological (heart rate and electrodermal activity), and hormonal response (salivary cortisol and Alpha-amylase) to this stressful situation in different moments (before VR task (anticipation), at the end of the task and 10 minutes later) in young people with problematic alcohol use (AU, n = 27), alcohol combined with cannabis consumption (AU + C, n = 10), as well as in a control group (CO, n = 33). Behavioral analysis revealed that the AU group displayed fewer entries into open arms than the CO group, whereas both experimental groups spent less time at the end of the open arms, as well as lower time by look down index compared to the CO group. Moreover, our VR EPM induced different psychophysiological responses in the different moments measured. In general, electrodermal activity seemed to be a good biomarker of recovery from a stressful situation, as once the exposure to the stressful situation ended, the AU + C group took longer to recover compared to the CO group. Regarding hormonal analyses, we observed a similar response pattern in all groups suggesting that our VR task was able to activate both stress systems. The alpha-amylase to cortisol ratio, proposed as a biomarker of stress systems dysregulation, was higher in the group of young participants with alcohol abuse. Interestingly, our VR EPM was able to induce a slight alcohol craving in both experimental groups. In conclusion, our results suggest certain subtle behavioral and physiological differences that could be used to detect young individuals at risk of future severe addictions or other stress-related comorbidities. Moreover, it could help us to develop prevention strategies focused on emotional, cognitive, and psychophysiological aspects.

Exploring the independent association of employment status to cancer survivors' health-related quality of life.

BACKGROUND: Having a job has been associated with better Health-Related Quality of Life (HRQOL) in cancer survivors. However, the sociodemographic and disease-related profiles characterizing the survivors being employed and those having better HRQOL largely overlap. The present study aims to discern the degree to which employment status is independently associated with cancer survivors' HRQOL or if it mainly reflects the impact of other sociodemographic and cancer-related variables. METHODS: Cross-sectional study on a heterogeneous sample of 772 working-age survivors of adult-onset cancer. An instrument specifically designed to assess HRQOL in cancer survivors and Multivariate Variance Analysis (MANOVA) were used. RESULTS: Survival phase, cancer type, and employment status showed the main effects on cancer survivors' HRQOL. In particular, being employed (vs unemployed) had the greatest positive association with HRQOL, affecting ten of the twelve HRQOL domains considered. Also, interaction effects highlighted the role of age (younger) and marital status (single) as risk factors for a greater negative impact of variables affecting the survivor's HRQOL. CONCLUSIONS: The application of a multivariate methodology sheds new light on two relevant issues for the cancer survivor's HRQOL: (i) the existence of differences between diagnostic groups that are not attributed to other variables such as sex, and (ii) the important and independent role that employment status plays. Comprehensive cancer survivorship care should focus more on high-risk groups and include having a job as an essential aspect to consider and prompt. The fact that the employment status is susceptible to change represents a valuable opportunity to care for the wellbeing of this population.

Design of a safety round model for intensive care units.

INTRODUCTION: Safety Rounds (SR) are an operational tool that allow knowing adherence to good practices, help identify risks and incidents in patient safety (PS), allowing improvement actions to be implemented. The objective of this work was the design of a procedure to perform SR in an Intensive Care Unit (ICU). METHODS: Preparation of a checklist for the development of SR in the ICU through the nominal group technique, with the participation of managers, middle managers and professionals from different disciplines and categories. In the first place, a group of experts agreed, based on the recommendations on good practices in PS, the definition of items, their coding, the criteria for compliance and the impact of non-compliance. Subsequently, its viability was determined through a cross-sectional study through the piloting of two SRs to adjust the items in real clinical practice conditions. RESULTS: A specific SR model for ICUs has been obtained through a checklist. The group of experts prepared a first list made up of 39 items of 6 essential dimensions and defined the method of implementation. Mean time to complete the two SRs was 85 min, including the briefing and subsequent debriefing. After the validation pilot, the dimensions were reduced to 5, 3 items were deleted, 2 items were transferred to another dimension and 3 items related to nosocomial infections and informed consent were modified. In addition, the data sources, the compliance criteria and their relative weight were redefined. The final list was considered useful and relevant to improve practice. CONCLUSIONS: Through a consensus methodology, a checklist has been built to be used in the RS of an ICU. This model can serve as a basis for its use in healthcare services with similar characteristics.

The influence of culture and cognitive reserve on the clinical presentation of behavioural-variant frontotemporal dementia.

Characterisation of the clinical profile of behavioural-variant frontotemporal dementia (bvFTD) has predominantly been based on Western samples. Some small studies have suggested that the clinical profile may differ in culturally and linguistically diverse populations. Additionally, there is evidence that patients from non-English speaking backgrounds may have more cognitive reserve, allowing them to tolerate more disease pathology before clinical symptoms emerge. This study aims to characterise the clinical profiles of patients with bvFTD from culturally diverse backgrounds. BvFTD patients were classified as Australian-born (Australian) or Culturally and Linguistically Diverse-English-speaking (CALD-English) and Culturally and Linguistically Diverse-Language Other Than English (CALD-LOTE). Clinical features, cognitive test performance and cognitive reserve were compared between groups. Voxel-based morphometry was used to examine the neural correlates of cognitive reserve. 107 patients with bvFTD (53 Australian, 36 CALD-English, 18 CALD-LOTE) and 51 controls were included. Analysis of neuropsychiatric features revealed more elation in Australian patients compared to CALD-English patients, with trends for CALD-LOTE patients to report more irritability. CALD-LOTE patients also had higher cognitive reserve and showed relatively greater verbal than non-verbal cognitive impairment. Neuroimaging analyses revealed that higher cognitive reserve was associated with lower integrity in the frontal-temporal regions associated with typical disease pathology in bvFTD. Our findings support the hypothesis that cognitive reserve may delay early cognitive decline in culturally and linguistically diverse patients, although these patients may still show poor verbal performance due to cultural testing biases. Clinically, these results highlight the need to consider cultural and linguistic background to inform the assessment of dementia.

A survey on deep learning applied to medical images: from simple artificial neural networks to generative models.

Deep learning techniques, in particular generative models, have taken on great importance in medical image analysis. This paper surveys fundamental deep learning concepts related to medical image generation. It provides concise overviews of studies which use some of the latest state-of-the-art models from last years applied to medical images of different injured body areas or organs that have a disease associated with (e.g., brain tumor and COVID-19 lungs pneumonia). The motivation for this study is to offer a comprehensive overview of artificial neural networks (NNs) and deep generative models in medical imaging, so more groups and authors that are not familiar with deep learning take into consideration its use in medicine works. We review the use of generative models, such as generative adversarial networks and variational autoencoders, as techniques to achieve semantic segmentation, data augmentation, and better classification algorithms, among other purposes. In addition, a collection of widely used public medical datasets containing magnetic resonance (MR) images, computed tomography (CT) scans, and common pictures is presented. Finally, we feature a summary of the current state of generative models in medical image including key features, current challenges, and future research paths.

CMRSegTools: An open-source software enabling reproducible research in segmentation of acute myocardial infarct in CMR images.

In the last decade, a large number of clinical trials have been deployed using Cardiac Magnetic Resonance (CMR) to evaluate cardioprotective strategies aiming at reducing the irreversible myocardial damage at the time of reperfusion. In these studies, segmentation and quantification of myocardial infarct lesion are often performed with a commercial software or an in-house closed-source code development thus creating a barrier for reproducible research. This paper introduces CMRSegTools: an open-source application software designed for the segmentation and quantification of myocardial infarct lesion enabling full access to state-of-the-art segmentation methods and parameters, easy integration of new algorithms and standardised results sharing. This post-processing tool has been implemented as a plug-in for the OsiriX/Horos DICOM viewer leveraging its database management functionalities and user interaction features to provide a bespoke tool for the analysis of cardiac MR images on large clinical cohorts. CMRSegTools includes, among others, user-assisted segmentation of the left-ventricle, semi- and automatic lesion segmentation methods, advanced statistical analysis and visualisation based on the American Heart Association 17-segment model. New segmentation methods can be integrated into the plug-in by developing components based on image processing and visualisation libraries such as ITK and VTK in C++ programming language. CMRSegTools allows the creation of training and testing data sets (labeled features such as lesion, microvascular obstruction and remote ROI) for supervised Machine Learning methods, and enables the comparative assessment of lesion segmentation methods via a single and integrated platform. The plug-in has been successfully used by several CMR imaging studies.

Transforming a public university hospital and its area of influence into a comprehensive resource in response to the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVES: The outbreak of COVID-19 has overwhelmed healthcare systems all over the world. The aim of this article is to describe the process of transforming the Vall d'Hebron University Hospital, the second largest hospital in Spain, into a COVID-19 centre coordinating response to the pandemic in its reference area. MATERIALS AND METHODS: The study draws on the experience of the authors in transforming the hospital into a comprehensive resource in response to the COVID-19 pandemic. The strategy is based on four central strategies: early planning, coordination of all healthcare agents in its reference area, definition of clear leadership roles, and the organisation of care based on multidisciplinary teams with minimal recruitment of new staff. RESULTS: The transformation strategy enabled the hospital to cope with the surge in patients without exceeding its capacity. During the response phases, which amounted to a period of 57 days, 3106 patients consulted the ER and 2054 were admitted, 346 of whom were treated at the ICU. To accommodate the number of adult COVID-19 patients, adult ICU availability was progressive increased by 371%, and ordinary beds increased by 240. A total of 671 staff members went on sick leave after testing positive for COVID-19. CONCLUSION: The transformation experience of the hospital provides insight into how effectively adapt the structures and functioning of large hospitals. The relevance of territorial coordination during the pandemic is stressed as an effective strategy that contributed coping the pandemic.

Silyl formates as hydrosilane surrogates for the transfer hydrosilylation of ketones.

A transfer hydrosilylation of ketones employing silyl formates as hydrosilane surrogates under mild conditions is presented. A total of 24 examples of ketones have been successfully converted to their corresponding silyl ethers with 61-99% yields in the presence of a PNHP-based ruthenium catalyst and silyl formate reagent. The crucial role of the ligand for the transformation is demonstrated.

Thermoluminescent studies of GdAlO3 powders.

The increasing use of thermoluminescence (TL) materials as radiation detectors with application in different areas of ionizing radiation has motivated research on new materials with adequate luminescent characteristics. In this work, experimental results gadolinium aluminate (GdAlO3) analyzed by thermoluminescent phenomenon under beta irradiation effect are studied. To prepare GdAlO3 powders the coprecipitation method was used. TL glow curve and other luminescent characteristics were analyzed using an automatic Lexsig Smart TL/OSL luminescent reader. TL glow curve showed four peaks with three prominent and well-defined peaks centered at 140, 230, and 270 °C. TL response as a function of beta radiation dose was linearity in the range from 1.1 up to 44 Gy. Kinetic parameters such as activation energy (E), frequency factor (s), and order of kinetics after the deconvolution of the TL glow curve were also determined using Chen's peak shape method. Experimental results show GdAlO3 as a potential luminescent host material for TL studies.

Validation of cardiac diffusion tensor imaging sequences: A multicentre test-retest phantom study.

Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish the accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI among 10 centres internationally. Phantoms comprising 0%-20% polyvinylpyrrolidone (PVP) were scanned with DTI using a product pulsed gradient spin echo (PGSE; N = 10 sites) sequence, and a custom motion-compensated spin echo (SE; N = 5) or stimulated echo acquisition mode (STEAM; N = 5) sequence suitable for cardiac DTI in vivo. A second identical scan was performed 1-9 days later, and the data were analysed centrally. The average mean diffusivities (MDs) in 0% PVP were (1.124, 1.130, 1.113) x 10-3  mm2 /s for PGSE, SE and STEAM, respectively, and accurate to within 1.5% of reference data from the literature. The coefficients of variation in MDs across sites were 2.6%, 3.1% and 2.1% for PGSE, SE and STEAM, respectively, and were similar to previous studies using only PGSE. Reproducibility in MD was excellent, with mean differences in PGSE, SE and STEAM of (0.3 ± 2.3, 0.24 ± 0.95, 0.52 ± 0.58) x 10-5  mm2 /s (mean ± 1.96 SD). We show that custom sequences for cardiac DTI provide accurate, precise, repeatable and reproducible measurements. Further work in anisotropic and/or deforming phantoms is warranted.

MiRNA-149 as a Candidate for Facial Clefting and Neural Crest Cell Migration.

Nonsyndromic cleft lip with or without palate (nsCL/P) ranks among the most common human birth defects and has a multifactorial etiology. Human neural crest cells (hNCC) make a substantial contribution to the formation of facial bone and cartilage and are a key cell type in terms of nsCL/P etiology. Based on increasing evidence for the role of noncoding regulatory mechanisms in nsCL/P, we investigated the role of hNCC-expressed microRNAs (miRNA) in cleft development. First, we conducted a systematic analysis of miRNAs expressed in human-induced pluripotent stem cell-derived hNCC using Affymetrix microarrays on cell lines established from 4 unaffected donors. These analyses identified 152 candidate miRNAs. Based on the hypothesis that candidate miRNA loci harbor genetic variation associated with nsCL/P risk, the genomic locations of these candidates were cross-referenced with data from a previous genome-wide association study of nsCL/P. Associated variants were reanalyzed in independent nsCL/P study populations. Jointly, the results suggest that miR-149 is implicated in nsCL/P etiology. Second, functional follow-up included in vitro overexpression and inhibition of miR-149 in hNCC and subsequent analyses at the molecular and phenotypic level. Using 3'RNA-Seq, we identified 604 differentially expressed (DE) genes in hNCC overexpressing miR-149 compared with untreated cells. These included TLR4 and JUNB, which are established targets of miR-149, and NOG, BMP4, and PAX6, which are reported nsCL/P candidate genes. Pathway analyses revealed that DE genes were enriched in pathways including regulation of cartilage development and NCC differentiation. At the cellular level, distinct hNCC migration patterns were observed in response to miR-149 overexpression. Our data suggest that miR-149 is involved in the etiology of nsCL/P via its role in hNCC migration.