Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing. METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region. RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes. CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Nephrosis in cattle associated with consumption of Ludwigia peploides (Onagraceae).

This paper describes an outbreak of nephrosis in cattle associated with the consumption of Ludwigia peploides in Tucuman province, northwestern Argentina. Affected cows exhibited submandibular and chest edema, lethargy and ataxia, and eventually succumbed to these conditions. These animals were grazing in a floodable area severely invaded by this plant. The disease affected 7 out of a herd of 67 cows. Horses and goats grazing in the same location were not affected. The main gross and histological lesion corresponded to a severe nephrosis. The disease is similar to the poisoning by Ludwigia peruviana reported in Colombia.

The brittle star genome illuminates the genetic basis of animal appendage regeneration.

Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited genomic resources. Here we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star genome is the most rearranged among echinoderms sequenced so far, featuring a reorganized Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression during brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, particularly during the proliferative phase of regeneration. Our findings emphasize the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems.

Value of the biomarker soluble tyrosine kinase 1 type fms (sFLT-1) in the diagnosis and prognosis of sepsis: a systematic review. / Valor del biomarcador tirosina quinasa 1 soluble tipo fms (sFLT-1) en el diagnóstico y pronóstico de la sepsis: una revisión sistemática.

INTRODUCTION: The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022. MATERIALS AND METHODS: A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry). RESULTS: The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction. CONCLUSIONS: It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker.

Telenursing as a tool in emergencies and disasters: A systematic review.

Telenursing as a tool in emergencies and disasters: a systematic review. BACKGROUND: Telenursing is an innovative strategy that allows nurses to care for patients in various situations with the help of technology. The aim of this systematic review is to analyse the current situation of telenursing in emergencies and disasters by means of a systematic review of the scientific literature. METHODS: A systematic review of the scientific literature was carried out following the PRISMA methodology. A systematic search was conducted using the CINAHL, Pubmed and Cochrane Library databases. Study selection and risk of bias were performed independently by pair of authors. RESULTS: A total of 14 publications were selected. The results of the study focus on two main themes; on the one hand, the benefits offered by telenursing in the field of emergency and disaster situations and, on the other hand, the perspective of professionals who use it or who are likely to do so. CONCLUSIONS: Telenursing brings benefits to the emergency department, such as improved clinical outcomes, fewer unnecessary visits to the department, enhanced nursing autonomy and reduced healthcare costs. Nurses have a positive attitude towards the use of this technology; however, more training and equipment are required to increase its effectiveness.

Use of tele-nursing in primary care: A qualitative study on its negative and positive aspects / Uso de teleenfermería en atención primaria: estudio cualitativo sobre sus aspectos negativos y positivos

Objective To analyze the opinions of nursing professionals on the current limitations and future potential of digital tools in healthcare. Design Qualitative and descriptive study. Location The study took place during an asynchronous MOODLE course on the use of ICT in healthcare, specifically aimed at nursing professionals. Participants The number of nurses enrolled in the course was 150. Methods A qualitative study was conducted focusing on the positive and negative aspects that telenursing can offer in the context of a Moodle training in new technologies for nurses. A thematic analysis was carried out following the method proposed by Braun and Clarke. Results In the end 68 nurses participated in the forum. Their statements, opinions and perceptions were analyzed and 28 descriptive codes were obtained and subsequently categorized into positive and negative aspects. Conclusions Nurses positively value the usefulness of digital tools and identify a wide range of benefits of telenursing in daily practice. At the same time, they point out crucial limitations that may slow down the adoption of telenursing, pointing to areas for improvement such as training and digital literacy of both patients and professionals. They consider that telenursing can humanise care, but insist on the need to prevent its use from increasing health inequalities. (AU)

Objetivo Analizar las opiniones de los profesionales de enfermería sobre las limitaciones actuales y el potencial futuro de las herramientas digitales en la atención sanitaria. Diseño Estudio cualitativo y descriptivo. Lugar El estudio se desarrolló durante un curso MOODLE asíncrono sobre el uso de las TIC en la atención sanitaria, dirigido específicamente a profesionales de enfermería. Participantes El número de enfermeras inscritas en el curso fue de 150. MétodosSe realizó un estudio cualitativo centrado en los aspectos positivos y negativos que puede ofrecer la teleenfermería en el contexto de una formación Moodle en nuevas tecnologías para enfermeras. Se realizó un análisis temático siguiendo el método propuesto por Braun y Clarke. Resultados Finalmente participaron en el foro 68 enfermeras. Se analizaron las declaraciones, las opiniones y las percepciones de las mismas, obteniéndose 28 códigos descriptivos que posteriormente se categorizaron en aspectos positivos y negativos. Conclusiones Las enfermeras valoran positivamente la utilidad de las herramientas digitales e identifican una amplia gama de beneficios de la teleenfermería en la práctica diaria. Al mismo tiempo, señalan limitaciones cruciales que pueden ralentizar la adopción de la teleenfermería, señalando áreas de mejora como la formación y la alfabetización digital tanto de pacientes como de profesionales. Consideran que la teleenfermería puede humanizar la asistencia, pero insisten en la necesidad de evitar que su uso aumente las desigualdades en salud. (AU)

Unlocking the secret life of blue mussels: Exploring connectivity in the Skagerrak through biophysical modeling and population genomics.

Knowledge of functional dispersal barriers in the marine environment can be used to inform a wide variety of management actions, such as marine spatial planning, restoration efforts, fisheries regulations, and invasive species management. Locations and causes of dispersal barriers can be studied through various methods, including movement tracking, biophysical modeling, demographic models, and genetics. Combining methods illustrating potential dispersal, such as biophysical modeling, with realized dispersal through, e.g., genetic connectivity estimates, provides particularly useful information for teasing apart potential causes of observed barriers. In this study, we focus on blue mussels (Mytilus edulis) in the Skagerrak-a marginal sea connected to the North Sea in Northern Europe-and combine biophysical models of larval dispersal with genomic data to infer locations and causes of dispersal barriers in the area. Results from both methods agree; patterns of ocean currents are a major structuring factor in the area. We find a complex pattern of source-sink dynamics with several dispersal barriers and show that some areas can be isolated despite an overall high dispersal capability. Finally, we translate our finding into management advice that can be used to sustainably manage this ecologically and economically important species in the future.

Effectiveness of a diagnostic algorithm for dengue based on an artificial neural network.

Introduction: Dengue is a disease with a wide clinical spectrum. The early identification of dengue cases is crucial but challenging for health professionals; therefore, it is necessary to have effective diagnostic instruments to initiate timely care. Objective: To evaluate the effectiveness of an algorithm based on an artificial neural network (ANN) to diagnose dengue in an endemic area. Methods: A single-center case-control study was conducted in a secondary-care hospital in Ciudad Obregón, Sonora. An algorithm was built with the official operational definitions, which was called the "direct algorithm," and for the ANN algorithm, the brain.js library was used. The data analysis was performed with the diagnostic tests of sensitivity, specificity, positive predictive value (ppv), and negative predictive value (npv), with 95% confidence intervals and Cohen's kappa index. Results: A total of 233 cases and 233 controls from 2022 were included. The ANN presented a sensitivity of 0.90 (95% CI [0.85, 0.94]), specificity of 0.82 (95% CI [0.77, 0.87]), npv of 0.91 (95% CI [0.87, 0.94]) and ppv of 0.81 (95% CI [0.76, 0.85]) and a kappa of 0.72. The direct algorithm had a sensitivity of 0.97 (95% CI [0.94, 0.99]), specificity of 0.96 (95% CI [0.92, 0.98]), npv 0.97 (95% CI [0.94, 0.98]), ppv 0.96 (95% CI [0.93, 0.98]) and kappa 0.93. Conclusions: The direct algorithm performed better than the ANN in the diagnosis of dengue.

Extra Virgin Olive Oil Phenolic Compounds Modulate the Gene Expression of Biomarkers Involved in Fibroblast Proliferation and Differentiation.

Extra virgin olive oil phenolic compounds have been identified as possible biostimulant agents against different pathological processes, including alterations in healing processes. However, there is little evidence on the molecular mechanisms involved in this process. The aim was to analyse the effect of hydroxytyrosol, tyrosol, and oleocanthal on fibroblast gene expression. PCR was used to determine the expression of different differentiation markers, extracellular matrix elements, and growth factors in cultured human fibroblasts CCD-1064Sk treated with different doses of hydroxytyrosol (10-5 M and 10-6 M), tyrosol (10-5 M and 10-6 M), and oleocanthal (10-6 M and 10-7 M). After 24 h of hydroxytyrosol treatment, increased expression of connective tissue growth factor, fibroblast growth factor (FGF), platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor ß1 (TGF-ß1), and their receptors was observed. Tyrosol and olecanthal modulated the expression of FGF and TGFßR1. All phytochemicals tested modified the expression of differentiation markers and extracellular matrix elements, increasing gene expression of actin, fibronectin, decorin, collagen I, and III. Phenolic compounds present in extra virgin olive could have a beneficial effect on tissue regeneration by modulating fibroblast physiology.

Use of tele-nursing in primary care: A qualitative study on its negative and positive aspects.

OBJECTIVE: To analyze the opinions of nursing professionals on the current limitations and future potential of digital tools in healthcare. DESIGN: Qualitative and descriptive study. LOCATION: The study took place during an asynchronous MOODLE course on the use of ICT in healthcare, specifically aimed at nursing professionals. PARTICIPANTS: The number of nurses enrolled in the course was 150. METHODS: A qualitative study was conducted focusing on the positive and negative aspects that telenursing can offer in the context of a Moodle training in new technologies for nurses. A thematic analysis was carried out following the method proposed by Braun and Clarke. RESULTS: In the end 68 nurses participated in the forum. Their statements, opinions and perceptions were analyzed and 28 descriptive codes were obtained and subsequently categorized into positive and negative aspects. CONCLUSIONS: Nurses positively value the usefulness of digital tools and identify a wide range of benefits of telenursing in daily practice. At the same time, they point out crucial limitations that may slow down the adoption of telenursing, pointing to areas for improvement such as training and digital literacy of both patients and professionals. They consider that telenursing can humanise care, but insist on the need to prevent its use from increasing health inequalities.

[An evaluation of teacher training to promote healthy and equitable relationships: transforming or reproducing?] / Evaluación de la formación a profesorado para promover relaciones saludables y equitativas: ¿transformar o reproducir?

OBJECTIVE: To evaluate the impact of the training on teacher capacity to implement Posem el Focus, a socio-educational intervention adapted from Lights4Violence to prevent the gender-based violence during adolescence. METHOD: Evaluation study of a training using qualitative methodology in Terrassa, 2019-2021. The socio-constructionist perspective was used to understand the impact of teacher training and its translation into educational practice. A purposive sampling of teachers (n=32) was carried out. A descriptive-interpretative analysis of the discourses was carried out based on the written productions of the participants in the training and their answers to some open questions. An explanatory theoretical framework was developed. RESULTS: Teachers reported acquiring concepts, developing new skills and modifying some attitudes. Teachers stated theoretical understanding of the sex-gender system, intersectionality and explicit and implicit violence. However, they reproduced gender stereotypes, did not understand the inclusive approach and pointed out not identifying implicit violence. Teachers perceived the training as useful and felt empowered to implement the intervention. No differences were identified in discursive production with respect to gender or age. CONCLUSIONS: Teacher training ensures minimum knowledge and facilitates the acquisition of some skills, although it does not achieve in-depth changes in attitudes. It is concluded that the training enables teachers to implement Posem el Focus, although it is recommended that it be reformulated.

Nurses' view of benefits, enablers and constraints to the use of digital health tools with patients: A cross-sectional study.

Introduction: Digital literacy helps patients to be more informed in order to make decisions about their health. Patient empowerment in the digital realm is a duty for all healthcare professionals, but nurses are the most numerous professionals in all healthcare systems worldwide. In addition, they have an important role in health education and patient follow-up. Therefore, the use of digital tools, by nurses to empower and help patients know more about their health, is crucial. Objective: This study was conducted to identify nurses' views on the benefits as well as constraints nurses encounter when using digital resources to empower and educate their patients. We sought to identify enablers that could help nurses use technology with their patients as a means to reinforce the care and advice they offer them. Methods: An online ad hoc questionnaire was answered by 848 currently employed Spanish nurses on the benefits of using digital media with their patients, as well as on the constraints and enablers during implementation. Results: The majority of the nurses considered that reliable digital information would reduce unnecessary consultations. In addition, they think that at least 50% of their patients could benefit from consulting information online. Among the constraints, nurses mainly pointed out the older age and low educational level of their patients. Younger nurses are the most likely nurses to see patient age as a problem. As for enablers, nurses pointed out the training offered to patients as well as digital tools being user-friendly for patients. Conclusions: It is crucial to work while following a lifelong learning strategy, with training from university education as well as training from healthcare institutions to reduce the digital gap that affects patients' digital empowerment.

Determination of ptaquiloside in ten species of Pteris in northwestern Argentina.

The toxic effect of ferns of the genus of Pteris in bovines is caused by ptaquiloside, the main carcinogenic toxin. In this study, ten species of Pteris fern in different phenologic stages and plant conditions were collected in northwest Argentina. The phytochemical analysis showed the presence of Pt in the recent collected samples (adults and young plants) but not in the herbarium specimens. The results show a great variation of Pt concentration that depends on the phenologic stage, plant condition, and collection site. Pt was measured in 6-4326 µg/g concentration, with a mean concentration of 644 µg/g. No Pt was detected in eight species of Pteris collected from herbarium samples; such results may be a false negative. It is important to notice that analysis of herbarium samples for Pt may not be a reliable method to determine its presence. It is important to further understand the potential toxicity caused by these ferns because of their effect on animals, public health, and the environment.

¿influyen los determinantes socioeconómicos en la oferta de los menús escolares? / Do socioeconomic determinants influence school menus?

Introducción: la oferta de menús escolares es un área relevante en las estrategias de salud. Objetivos: analizar las diferencias en el cumplimiento de las frecuencias recomendadas de alimentos y otras características del comedor escolar en los centros educativos según su titularidad y la renta del barrio. Métodos: se ofreció la revisión trienal a los centros escolares de la ciudad de Barcelona que disponían de servicio de comedor. En los tres cursos académicos, participaron 341 centros: 175 públicos y 165 de titularidad privada. Para observar si existían diferencias, se utilizó la prueba de Pearson Chi-cuadrado o el test exacto de Fisher según el caso. Los análisis se realizaron con el programa estadístico STATA SE/15. Resultados: no se encontraron diferencias significativas según el nivel socioeconómico del barrio del centro educativo. Los centros educativos privados y concertados presentaban un menor cumplimiento en la pasta (11,1 %), las carnes rojas y procesadas (24,7 %), la carne total (7,4 %) y la fruta fresca (12,1 %), así como un menor uso del aceite recomendado para cocinar (13,1 %). Por el contrario, en los centros educativos públicos se observaba un menor cumplimiento en la recomendación del tipo de aceite para freír (16,9 %). Conclusiones: en los centros privados y concertados es necesario recomendar mejoras en la adecuación de las raciones. Se debería indagar en las causas que pueden explicar esta menor adecuación en varios aspectos como en el cumplimiento de las adecuaciones en estos centros.(AU)

Introduction: the components of school menus is an important area in health strategies.Objectives: the aim of this study was to analyse differences in adherence to recommended food frequencies and other characteristics of schoolmeals in educational centres according to the type of school and neighbourhood income.Method: schools in the city of Barcelona with a lunch service were offered a three-year review. In the three academic years, 341 schoolsparticipated: 175 were public and 165 were private. To identify any differences, the Pearson Chi-squared test or Fisher exact test were used, asappropriate. Statistical analyses were performed with the STATA SE/15 programme.Results: no statistically significant differences were found by the socioeconomic level of the school neighbourhood. Private and subsidisedschools showed lower adherence to recommendations on pasta (11.1 %), red and processed meat (24.7 %), total meat (7.4 %) and fresh fruit(12.1 %), and lower use of the recommended cooking oil (13.1 %). In contrast, public schools showed lower adherence to the recommendedtype of frying oil (16.9 %).Conclusions: in private and subsidised schools, improvements should be recommended on the frequency of intake of certain foods. Futurestudies should examine the causes of lower adherence to certain recommendations in these centres.(AU)

Usefulness of Preoperative Determination of Serum MR-ProAdrenomedullin Levels to Predict the Need for Postoperative Organ Support in Abdominal Oncological Surgery.

The need for postoperative organic support is associated with patient outcomes. Biomarkers may be useful for detecting patients at risk. MR-ProADM is a novel biomarker with an interesting profile that can be used in this context. The main objective of this study was to verify whether there was an association between the preoperative serum levels of MR-ProADM and the need for organic support after elective abdominal cancer surgery, and to determine the preoperative MR-ProADM value that predicts the need for postoperative organic support. This was a multicenter prospective observational study conducted by four tertiary hospitals in Spain between 2017 and 2018. Plasma samples were collected for the quantification of MR-ProADM from adults who underwent major abdominal surgery during 2017-2018. The primary outcome was the need for organic support in the first seven postoperative days and its association with the preoperative levels of MR-ProADM, and the secondary outcome was the preoperative levels of MR-ProADM in the study population. This study included 370 patients with a mean age of 67.4 ± 12.9 years. Seventeen percent (63 patients) required some postoperative organic support measures in the first week. The mean preoperative value of MR-ProADM in patients who required organic support was 1.16 ± 1.15 nmol/L. The AUC-ROC of the preoperative MR-ProADM values associated with the need for organic support was 0.67 (95% CI: 0.59-0.75). The preoperative MR-ProADM value, which showed the best compromise in sensitivity and specificity for predicting the need for organic support, was 0.70 nmol/L. The negative predictive value was 91%. A multivariate analysis confirmed that a preoperative level of MR-ProADM ≥ 0.70 nmol/L is an independent factor associated with risk of postoperative organic support (OR 2, 6). Elevated preoperative MR-ProADM levels are associated with the need for postoperative organic support. Therefore, MR-ProADM may be a useful biomarker for perioperative risk assessment.

The Benefits of Olive Oil for Skin Health: Study on the Effect of Hydroxytyrosol, Tyrosol, and Oleocanthal on Human Fibroblasts.

Fibroblasts contribute to maintaining tissue integrity and homeostasis and are a key cell population in wound healing. This cell population can be stimulated by some bioactive compounds such as extra virgin olive oil (EVOO) polyphenols. The aim of this study was to determine the effects of hydroxytyrosol (htyr), tyrosol (tyr), and oleocanthal (ole) phenolic compounds present in EVOO on the proliferation, migration, cell cycle, and antigenic profile of cultured human fibroblasts. CCD-1064Sk human fibroblast cells were treated for 24 h with each polyphenol at doses ranging 10-5 to 10-9 M. Cell proliferation was evaluated using the MTT spectrophotometric technique, migration capacity by culture insert assay, and cell cycle and antigenic profile with flow cytometry. Cell proliferation was significantly increased by treatment with all compounds. The highest increases followed treatments with htyr or tyr at doses of 10-5 or 10-6 M and with ole at 10-6 and 10-7 M, and these compounds and doses were used for assays of antigenic profile, cell cycle, and migration. During the first few hours after treatment, increased fibronectin and α-actin expressions and greater cell migration were observed, with no cell cycle changes. In conclusion, these in vitro results suggest that phenolic compounds in EVOO might contribute to wound healing through action on fibroblasts related to tissue regeneration.

[Do socioeconomic determinants influence school menus?] / ¿Influyen los determinantes socioeconómicos en la oferta de los menús escolares?

Introduction: Introduction: the components of school menus is an important area in health strategies. Objectives: the aim of this study was to analyse differences in adherence to recommended food frequencies and other characteristics of school meals in educational centres according to the type of school and neighbourhood income. Method: schools in the city of Barcelona with a lunch service were offered a three-year review. In the three academic years, 341 schools participated: 175 were public and 165 were private. To identify any differences, the Pearson Chi-squared test or Fisher exact test were used, as appropriate. Statistical analyses were performed with the STATA SE/15 programme. Results: no statistically significant differences were found by the socioeconomic level of the school neighbourhood. Private and subsidised schools showed lower adherence to recommendations on pasta (11.1 %), red and processed meat (24.7 %), total meat (7.4 %) and fresh fruit (12.1 %), and lower use of the recommended cooking oil (13.1 %). In contrast, public schools showed lower adherence to the recommended type of frying oil (16.9 %). Conclusions: in private and subsidised schools, improvements should be recommended on the frequency of intake of certain foods. Future studies should examine the causes of lower adherence to certain recommendations in these centres.

Introducción: Introducción: la oferta de menús escolares es un área relevante en las estrategias de salud. Objetivos: analizar las diferencias en el cumplimiento de las frecuencias recomendadas de alimentos y otras características del comedor escolar en los centros educativos según su titularidad y la renta del barrio. Métodos: se ofreció la revisión trienal a los centros escolares de la ciudad de Barcelona que disponían de servicio de comedor. En los tres cursos académicos, participaron 341 centros: 175 públicos y 165 de titularidad privada. Para observar si existían diferencias, se utilizó la prueba de Pearson Chi-cuadrado o el test exacto de Fisher según el caso. Los análisis se realizaron con el programa estadístico STATA SE/15. Resultados: no se encontraron diferencias significativas según el nivel socioeconómico del barrio del centro educativo. Los centros educativos privados y concertados presentaban un menor cumplimiento en la pasta (11,1 %), las carnes rojas y procesadas (24,7 %), la carne total (7,4 %) y la fruta fresca (12,1 %), así como un menor uso del aceite recomendado para cocinar (13,1 %). Por el contrario, en los centros educativos públicos se observaba un menor cumplimiento en la recomendación del tipo de aceite para freír (16,9 %). Conclusiones: en los centros privados y concertados es necesario recomendar mejoras en la adecuación de las raciones. Se debería indagar en las causas que pueden explicar esta menor adecuación en varios aspectos como en el cumplimiento de las adecuaciones en estos centros.

pH-Selective Reactions to Selectively Reduce Cancer Cell Proliferation: Effect of CaS Nanostructures in Human Skin Melanoma and Benign Fibroblasts.

An acidic extracellular pH value (pHe) is characteristic of many cancers, in contrast to the physiologic pHe found in most benign cells. This difference in pH offers a unique opportunity to design and engineer chemicals that can be employed for pH-selective reactions in the extracellular fluid of cancer cells. The viability of human skin melanoma and corresponding fibroblasts exposed to CaS dispersions is reported. The viability of melanoma cells decreases with CaS dispersion concentration and reaches 57% at 3%, a value easily distinguishable from melanoma control experiments. In contrast, the viability of benign fibroblasts remains nearly constant within experimental error over the range of dispersion concentrations studied. The CaS dispersions facilitate vinculin delocalization in the cytoplasmic fluid, a result consistent with improved focal adhesion kinase (FAK) regulation in melanoma cells. Thermodynamic considerations are consistent with the formation of H 2 S from CaS in the presence of protons. The thermodynamic prediction is verified in independent experiments with solid CaS and acidic aqueous solutions. The amount of H 2 S formed decreases with pH. An activation energy for the process of (30 ± 10) kJ/mol in the temperature range of 280 to 330 K is estimated from initial rate measurements as a function of temperature. The total Gibbs energy minimization approach was employed to establish the distribution of sulfides-including H 2 S in the gas and aqueous phases-from the dissociation of CaS as a function of pH to mimic physiologically relevant pH values. Theoretical calculations suggest that partially protonated CaS in solution can be stable until the sulfur atom bonds to two hydrogen atoms, resulting in the formation of Ca2+ and H 2 S , which can be solvated and/or released to the gas phase. Our results are consistent with a model in which CaS is dissociated in the extracellular fluid of melanoma cells selectively. The results are discussed in the context of the potential biomedical applications of CaS dispersions in cancer therapies.

Modulation of Osteogenic Gene Expression by Human Osteoblasts Cultured in the Presence of Bisphenols BPF, BPS, or BPAF.

Bone effects attributed to bisphenols (BPs) include the inhibition of growth and differentiation. This study analyzes the effect of BPA analogs (BPS, BPF, and BPAF) on the gene expression of the osteogenic markers RUNX2, osterix (OSX), bone morphogenetic protein-2 (BMP-2), BMP-7, alkaline phosphatase (ALP), collagen-1 (COL-1), and osteocalcin (OSC). Human osteoblasts were obtained by primary culture from bone chips harvested during routine dental work in healthy volunteers and were treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Untreated cells were used as controls. Real-time PCR was used to determine the expression of the osteogenic marker genes RUNX2, OSX, BMP-2, BMP-7, ALP, COL-1, and OSC. The expression of all studied markers was inhibited in the presence of each analog; some markers (COL-1; OSC, BMP2) were inhibited at all three doses and others only at the highest doses (10-5 and 10-6 M). Results obtained for the gene expression of osteogenic markers reveal an adverse effect of BPA analogs (BPF, BPS, and BPAF) on the physiology of human osteoblasts. The impact on ALP, COL-1, and OSC synthesis and therefore on bone matrix formation and mineralization is similar to that observed after exposure to BPA. Further research is warranted to determine the possible contribution of BP exposure to the development of bone diseases such as osteoporosis.