The Effect of Gelatin Source on the Synthesis of Gelatin-Methacryloyl and the Production of Hydrogel Microparticles.

Gelatin methacryloyl (GelMA) is widely used for the formulation of hydrogels in diverse biotechnological applications. After the derivatization of raw gelatin, the degree of functionalization (DoF) is an attribute of particular interest as the functional residues are necessary for crosslinking. Despite progress in the optimization of the process found in the literature, a comparison of the effect of raw gelatin on the functionalization is challenging as various approaches are employed. In this work, the modification of gelatin was performed at room temperature (RT), and eight different gelatin products were employed. The DoF proved to be affected by the bloom strength and by the species of gelatin at an equal reactant ratio. Furthermore, batch-to-batch variability of the same gelatin source had an effect on the produced GelMA. Moreover, the elasticity of GelMA hydrogels depended on the DoF of the protein as well as on bloom strength and source of the raw material. Additionally, GelMA solutions were used for the microfluidic production of droplets and subsequent crosslinking to hydrogel. This process was developed as a single pipeline at RT using protein concentrations up to 20% (w/v). Droplet size was controlled by the ratio of the continuous to dispersed phase. The swelling behavior of hydrogel particles depended on the GelMA concentration.

Fragile X Syndrome in children.

Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.

El síndrome de X frágil es causado por la expansión de tripletas CGG en el gen FMR1, el cual genera cambios epigenéticos que silencian su expresión. La ausencia de la proteína codificada por este gen, la FMRP, causa disfunción celular, llevando a deficiencia en el desarrollo cerebral y anormalidades funcionales. Las manifestaciones físicas y neurológicas de la enfermedad aparecen en edades tempranas y pueden sugerir el diagnóstico. Sin embargo, este debe ser confirmado por pruebas moleculares. El síndrome afecta múltiples aspectos de la vida diaria y representa una alta carga para los individuos afectados y para sus familias. El síndrome de C frágil es la causa monogénica más común de discapacidad intelectual y trastornos del espectro autista; por ende, el diagnóstico debe sospecharse en todo paciente con retraso del neurodesarrollo. Intervenciones tempranas podrían mejorar el pronóstico funcional de pacientes con síndrome de X frágil, impactando significativamente su calidad de vida y funcionamiento. Por lo tanto, la atención en salud de niños con síndrome de X frágil debe incluir un abordaje multidisciplinario.

On the reproducibility of extrusion-based bioprinting: round robin study on standardization in the field.

The outcome of three-dimensional (3D) bioprinting heavily depends, amongst others, on the interaction between the developed bioink, the printing process, and the printing equipment. However, if this interplay is ensured, bioprinting promises unmatched possibilities in the health care area. To pave the way for comparing newly developed biomaterials, clinical studies, and medical applications (i.e. printed organs, patient-specific tissues), there is a great need for standardization of manufacturing methods in order to enable technology transfers. Despite the importance of such standardization, there is currently a tremendous lack of empirical data that examines the reproducibility and robustness of production in more than one location at a time. In this work, we present data derived from a round robin test for extrusion-based 3D printing performance comprising 12 different academic laboratories throughout Germany and analyze the respective prints using automated image analysis (IA) in three independent academic groups. The fabrication of objects from polymer solutions was standardized as much as currently possible to allow studying the comparability of results from different laboratories. This study has led to the conclusion that current standardization conditions still leave room for the intervention of operators due to missing automation of the equipment. This affects significantly the reproducibility and comparability of bioprinting experiments in multiple laboratories. Nevertheless, automated IA proved to be a suitable methodology for quality assurance as three independently developed workflows achieved similar results. Moreover, the extracted data describing geometric features showed how the function of printers affects the quality of the printed object. A significant step toward standardization of the process was made as an infrastructure for distribution of material and methods, as well as for data transfer and storage was successfully established.

Cross-Sectional Study on Oral Health-Related Quality of Life Using OHIP-14 in Migrants Children in Melilla (Spain).

Quality of life is a parameter that not only evaluates clinical parameters, but also refers to the perception of the individual in his or her sociocultural context. It also refers to psychosocial aspects that have a very important impact on people's lives. Oral health-related quality of life (OHRQoL) must also be considered when assessing oral health in any population for which an oral health program is to be developed. On this premise, and taking into account the precarious situation of refugee children housed in the Temporary Center for Migrants (CETI) in Melilla (Spain), a study was conducted to assess the oral health and OHRQoL of the children housed in the aforementioned facility. For this purpose, the 120 children in care at the time of the study underwent a basic epidemiological examination according to the recommendations of the World Health Organization (WHO), and their OHRQoL was assessed using the specific OHIP-14 questionnaire. The results show a state of oral health with a high caries prevalence (95%), high DMFT, and dft indices for the studied population. The oral health-related quality of life perceived by these children shows that pain and psychological discomfort are the areas rated worst by them. Thus, it is concluded that it is important to implement specific oral health programs for this population, based on caries prevention and pain management, which must also take into account the psychological and sociocultural aspects that have accompanied their lives.

Fragile X Syndrome in children

Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.

El síndrome de X frágil es causado por la expansión de tripletas CGG en el gen FMR1, el cual genera cambios epigenéticos que silencian su expresión. La ausencia de la proteína codificada por este gen, la FMRP, causa disfunción celular, llevando a deficiencia en el desarrollo cerebral y anormalidades funcionales. Las manifestaciones físicas y neurológicas de la enfermedad aparecen en edades tempranas y pueden sugerir el diagnóstico. Sin embargo, este debe ser confirmado por pruebas moleculares. El síndrome afecta múltiples aspectos de la vida diaria y representa una alta carga para los individuos afectados y para sus familias. El síndrome de C frágil es la causa monogénica más común de discapacidad intelectual y trastornos del espectro autista; por ende, el diagnóstico debe sospecharse en todo paciente con retraso del neurodesarrollo. Intervenciones tempranas podrían mejorar el pronóstico funcional de pacientes con síndrome de X frágil, impactando significativamente su calidad de vida y funcionamiento. Por lo tanto, la atención en salud de niños con síndrome de X frágil debe incluir un abordaje multidisciplinario.

Analytics in Extrusion-Based Bioprinting: Standardized Methods Improving Quantification and Comparability of the Performance of Bioinks.

Three-dimensional bioprinting and especially extrusion-based printing as a most frequently employed method in this field is constantly evolving as a discipline in regenerative medicine and tissue engineering. However, the lack of relevant standardized analytics does not yet allow an easy comparison and transfer of knowledge between laboratories regarding newly developed bioinks and printing processes. This work revolves around the establishment of a standardized method, which enables the comparability of printed structures by controlling for the extrusion rate based on the specific flow behavior of each bioink. Furthermore, printing performance was evaluated by image-processing tools to verify the printing accuracy for lines, circles, and angles. In addition, and complementary to the accuracy metrics, a dead/live staining of embedded cells was performed to investigate the effect of the process on cell viability. Two bioinks, based on alginate and gelatin methacryloyl, which differed in 1% (w/v) alginate content, were tested for printing performance. The automated image processing tool reduced the analytical time while increasing reproducibility and objectivity during the identification of printed objects. During evaluation of the processing effect of the mixing of cell viability, NIH 3T3 fibroblasts were stained and analyzed after the mixing procedure and after the extrusion process using a flow cytometer, which evaluated a high number of cells. It could be observed that the small increase in alginate content made little difference in the printing accuracy but had a considerable strong effect on cell viability after both processing steps.

A Novel Approach for the Manufacturing of Gelatin-Methacryloyl.

Gelatin and its derivatives contain cell adhesion moieties as well as sites that enable proteolytic degradation, thus allowing cellular proliferation and migration. The processing of gelatin to its derivatives and/or gelatin-containing products is challenged by its gelation below 30 ∘C. In this study, a novel strategy was developed for the dissolution and subsequent modification of gelatin to its derivative gelatin-methacryloyl (GelMA). This approach was based on the presence of urea in the buffer media, which enabled the processing at room temperature, i.e., lower than the sol-gel transition point of the gelatin solutions. The degree of functionalization was controlled by the ratio of reactant volume to the gelatin concentration. Hydrogels with tailored mechanical properties were produced by variations of the GelMA concentration and its degree of functionalization. Moreover, the biocompatibility of hydrogels was assessed and compared to hydrogels formulated with GelMA produced by the conventional method. NIH 3T3 fibroblasts were seeded onto hydrogels and the viability showed no difference from the control after a three-day incubation period.

First Line Treatments for Newly Diagnosed Primary Immune Thrombocytopenia in Children: A Systematic Review and Network Meta-analysis.

BACKGROUND: The first-line interventions in immune thrombocytopenia (ITP) include intravenous polyclonal immunoglobulins (IVIg), corticosteroids and anti-D immunoglobulin (anti-D). OBJECTIVE: We aimed to compare the effectiveness and safety of first line treatments for newlydiagnosed primary ITP in children to increase the platelet count. METHODS: We searched MEDLINE, EMBASE, LILACS and the Cochrane Central register of Controlled Trials (CENTRAL); and included the clinical trials. We performed the statistical analysis in R. RESULTS: We included 12 studies for meta-analysis. Compared with IVIG 2g/kg, response rates were lower for prednisone 2mg/kg at 72 hours [RR 0.04 (95% CI 0.0 to 0.68)] and at 7 days [RR 0.23 (95% CI 0.08 to 0.67)]; at 48 hours, methylprednisolone 30mg/kg also showed lower response rates [RR 0.72 (95% CI 0.52 to 0.99)]. IVIG 2g/kg and 2.5g/kg had less adverse effects than Anti- D, methylprednisolone and IVIG 0.8g/kg. For rising platelet count, no statistical differences were found at 24 hours or in 7 days; at 48 hours, IVIG 2g/kg showed better results than Anti-D 75µg/kg [MD -58.84 (95% CI -87.02 to -25.66)]. After a month, platelet count with IVIG 2g/kg was higher than Anti-D 50 and 75µg/kg [-82.03 (95% CI -102.60 to -61.46) and -78.77 (95% CI -97.80 to - 59.74), respectively], but lower than methylprednisolone 50mg/kg [MD 118 (95% CI 3.88 to 232.12)]. CONCLUSION: The total platelet count rises higher in early and late phases with IVIG than Anti-D, but in long term it is higher with methylprednisolone. Additionally, IVIG causes less adverse effects than Anti-D and corticosteroids.

Percepciones y conocimientos de pacientes y cuidadores sobre cuidados paliativos, de la ciudad de Medellín (Colombia) / Perceptions and kwoledge about palliative care of patients and carers in Medellin, Colombia

Los cuidados paliativos (CP) mejoran la calidad de vida de pacientes y familias que se enfrentan a problemas asociados con enfermedades amenazantes para la vida, mediante la prevención y alivio del sufrimiento. Sin embargo, diversos estudios muestran bajo conocimiento y percepciones contradictorias frente a los efectos de estos cuidados. Esta investigación indagó sobre la percepción y el nivel de conocimiento sobre los CP de pacientes y cuidadores, en la ciudad de Medellín, mediante una metodología mixta con 19 personas (63.2% cuidadores). No se encontraron diferencias respecto a los conocimientos y percepciones entre ambos grupos (p >.05). Se encontró un nivel de conocimientos general aceptable, exceptuando el conocimiento referente a los síntomas que desde los CP se abarcan y los profesionales encargados de brindar estos cuidados. Así mismo, se encontró que según la percepción que tuvieron cui-dadores y pacientes, los CP mejoran la calidad de vida, ayudan a resignificar la muerte y disminuyen la carga asociada a la enfermedad

Palliative care improve the quality of life of patients and families that face problems associated with life-threatening diseases, through prevention and suffering relief. However, many studies show low knowledge and contradictory perceptions regarding the effects of this type of care. This study examined the perception and level of knowledge about palliative care of patients and carers in the city of Medellin, using mixed methods with 19 participants (63% are carers). There were no differences found between both groups regarding knowledge and perceptions (p >.05). It was found an acceptable level of knowledge, except for knowledge concerning the symptoms that palliative care covers and the professionals in charge of providing this. Likewise, it was found that, according to the perception that patients and carers had, palliative care improves the quality of life, it helps to reconsider the meaning of death, and reduces the load associated with the disease