Cross-Cultural Validation of the RosaQoL Scale in Spanish Language. / Validación transcultural al idioma español de la escala RosaQoL.

INTRODUCTION: Rosacea is a chronic disease negatively impacting the patients' quality of life and mental health. The Rosacea Quality of Life (RosaQoL) scale could be a useful tool to monitor patients while on therapy vs rosacea, as it measures the impact on quality of life and helps individualize treatment to meet the patients' needs. RosaQoL is a validated scale that can be completed within a few minutes. MATERIALS AND METHODS: The original scale was translated and back translated by 2 native translators, with input from an expert committee when necessary. This version was tested on 21 patients to ensure proper understanding. Psychometric characteristics and validity were determined using various measures (sensitivity and specificity via ROC curve and internal consistency via Cronbach's alpha). The correlation between RosaQoL and SF-12 scales was assessed using Pearson correlation coefficients. RESULTS: A total of 531 participants responded to the scale (481 with rosacea and 50 controls). The scale demonstrated excellent sensitivity and specificity (ROC curve, 0.96; 95%CI, 0.92-0.99) and high internal consistency (Cronbach's alpha, 0.96). RosaQoL correlated with SF-12. A higher score on the RosaQoL scale was associated with worse quality of life in all dimensions of the SF-12 scale. CONCLUSIONS: The Spanish version of the RosaQoL scale exhibits psychometric characteristics, which are similar to the original scale. Also, the RosaQoL scale is useful to assess the quality of life of patients with rosacea.

Apoptosis-modulatory miR-361-3p as a novel treatment target in endocrine-responsive and endocrine-resistant breast cancer.

Breast cancer (BC) is the most diagnosed cancer in women worldwide. In estrogen receptor (ER)-positive disease, anti-estrogens and aromatase inhibitors (AI) improve patient survival; however, many patients develop resistance. Dysregulation of apoptosis is a common resistance mechanism; thus, agents that can reinstate the activity of apoptotic pathways represent promising therapeutics for advanced drug-resistant disease. Emerging targets in this scenario include microRNAs (miRs). To identify miRs modulating apoptosis in drug-responsive and -resistant BC, a high-throughput miR inhibitor screen was performed, followed by high-content screening microscopy for apoptotic markers. Validation demonstrated that miR-361-3p inhibitor significantly increases early apoptosis and reduces proliferation of drug-responsive (MCF7), plus AI-/antiestrogen-resistant derivatives (LTED, TamR, FulvR), and ER- cells (MDA-MB-231). Importantly, proliferation-inhibitory effects were observed in vivo in a xenograft model, indicating the potential clinical application of miR-361-3p inhibition. RNA-seq of tumour xenografts identified FANCA as a direct miR-361-3p target, and validation suggested miR-361-3p inhibitor effects might be mediated in part through FANCA modulation. Moreover, miR-361-3p inhibition resulted in p53-mediated G1 cell cycle arrest through activation of p21 and reduced BC invasion. Analysis of publicly available datasets showed miR-361-3p expression is significantly higher in primary breast tumours vspaired normal tissue and is associated with decreased overall survival. In addition, miR-361-3p inhibitor treatment of BC patient explants decreased levels of miR-361-3p and proliferation marker, Ki67. Finally, miR-361-3p inhibitor showed synergistic effects on BC growth when combined with PARP inhibitor, Olaparib. Together, these studies identify miR-361-3p inhibitor as a potential new treatment for drug-responsive and -resistant advanced BC.

Inguinal lymph nodes agenesia in a patient with Schimmelpenning-Feuerstein-Mims syndrome with proven somatic KRAS mutation.

Schimmelpenning-Feuerstein-Mims (SFM) syndrome is a neurocutaneous disorder that can affect many body systems. The principal and most characteristic anomalies are craniofacial naevus sebaceous in association with neurological, ocular and skeletal findings. The presence of vascular malformations in this condition is unusual; nevertheless, vascular malformations have been suggested by many authors to be part of the spectrum of the same disease. Few cases have been published on the association of SFM with lymphatic malformations. This syndrome is categorized as a mosaic RASopathy due to postzygotic mutations in the HRAS, KRAS or NRAS genes. These genes are involved in the RAF-MEK-ERK signalling pathway, which is activated by mutant cells, increasing cellular proliferation. These mutations have been found only in naevus sebaceous cells, and may be also the explanation for many of the associated pathologies. We report a case of an 18-year-old boy diagnosed with SFM syndrome associated with lymphatic malformation in the legs and agenesia of the inguinal lymph nodes. The lymphatic alterations were diagnosed by gammography of the legs. The genetic diagnosis was confirmed by the presence of a KRAS postzygotic mutation in naevus sebaceous cells of a skin specimen. Genetically confirmed cases of mosaic RASopathies should be used to more accurately characterize phenotypic presentations of this syndrome and develop a future therapeutic strategy, such as molecular targeted therapy.

Documento de consenso español para el algoritmo de tratamiento de la rosácea / Spanish Consensus Document on the Treatment Algorithm for Rosacea

Las últimas evidencias científicas y la incorporación de nuevos fármacos al arsenal terapéutico de la rosácea hacen necesario revisar y actualizar los criterios y estrategias de tratamiento. Con este fin, un grupo de 15 dermatólogos expertos en esta enfermedad aportaron y discutieron acerca de las diferentes terapias y los criterios de respuesta y cambio de tratamiento. Partiendo de la revisión crítica de la bibliografía y de la exposición de los hábitos de los dermatólogos españoles en su práctica clínica, se formularon distintas propuestas que fueron debatidas teniendo en consideración tanto la experiencia profesional como las preferencias de los pacientes o los criterios de equidad. Una vez validadas las propuestas, se formularon las recomendaciones finales que, junto con la evidencia aportada por las principales guías y estudios internacionales, dieron lugar al presente documento. El objetivo de este consenso es ofrecer al dermatólogo un enfoque práctico para abordar la rosácea

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea

A micro-Raman and X-ray study of erupted submarine pyroclasts from El Hierro (Spain) and its' astrobiological implications.

The pumice volcanic samples could have possible connections to the evolution of life and give us insight about their bio-geochemical processes related. In this regard, the samples from the volcanic eruption from La Restinga (El Hierro, Spain) in 2011 have been mainly studied by means of Raman spectroscopy. The research also includes analysis of XRD, Scanning Electron Microscopy and Optical Microscopy to support the Raman analysis. The results show that the Raman methods and mineral analyses are in strong agreement with the results obtained from other authors and techniques. The internal white foamy core (WFC) of the studied pumice samples shows amorphous silica, Fe-oxides, Ti-oxides, quartz, certain sulfates, carbonates, zeolites and organics. On the other hand, the external part (dark crust - DC) of these samples mainly presents primary-sequence mineralogy combined with some secondary alteration minerals such as olivine, feldspar, pyroxene, amorphous silica, and Fe-oxide. Raman spectroscopy detected other minerals not yet reported on these samples like barite, celestine and lepidocrocite. Also, the different chemometric and calibration methods for Raman spectroscopy in elemental composition, mineral classification and structural characterization has been successfully applied. From the astrobiological perspective, the research was also complemented with comparisons to other similar samples from terrestrial analogs. The main consideration was taking into account the proposed hypothesis regarding the potential behavior of the pumice as a substrate for the evolution of life. Furthermore, the detailed analysis from La Restinga eruption is coherent with the mineral phases and processes discussed from previous literature. The white internal part fulfills the conditions to work as an organic reservoir, confirmed by the detection of organic matter and selected minerals that could be used as energy sources for bacterial communities. The external layers of the samples work as a shielding layer to protect the organics from decay in extreme conditions. Finally, here we have demonstrated that the characteristics and advantages of Raman spectroscopy could help to assess and understand the possible biogenicity and alteration processes of any geological sample to be found on Mars.

Reproductive Ontogeny and the Evolution of Morphological Diversity in Conifers and Other Plants.

Biologists often study morphological evolution through form and function relationships. But biological structures can perform multiple functional roles, complicating efforts to understand the evolutionary significance of any one relationship. Plant reproductive organs perform multiple roles in a sequence, however, which provides a unique opportunity to understand how structures evolve to meet multiple functional demands. Using conifers as a study group, we discuss how a shared developmental trajectory links the performance of sequential functional roles. Variation in development among lineages can underlie morphological diversity; pollination-stage seed cones in Pinaceae conifers function similarly but show diverse forms reflecting differences in developmental rate. As cones develop further, the morphologies that they use to perform later functional roles are influenced by the specific developmental patterns used to meet earlier demands, which may ultimately limit morphological diversity. However, we also show how selective pressures relating to the final functional stage (seed dispersal) may influence cone anatomy and morphology over all previous stages, highlighting the complex linkages among form, function, and development. We end by discussing the potential relationships between functional ontogeny and morphological disparity in plant reproductive structures more broadly, suggesting that the complex functional roles associated with seed plant reproduction probably underlie the high disparity in this group.

Spanish Consensus Document on the Treatment Algorithm for Rosacea. / Documento de consenso español para el algoritmo de tratamiento de la rosácea.

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea.

Rapid growth rate is associated with poor prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) represents the most common form of skin cancer after basal cell carcinoma, and can be both locally invasive and metastatic to distant sites. Growth rate (GR) has been poorly evaluated in cSCC, despite clinical evidence suggesting that GR is an important risk factor in cSCC. AIM: To analyse the influence of GR in cSCC prognosis. METHODS: We retrospectively evaluated GR in a series of 90 cSCCs and tried to correlate GR with prognosis in cSCC. RESULTS: We demonstrated that tumours with a GR of > 4 mm/month exhibit a higher risk of nodal progression and a shorter progression time to lymph node metastasis in cSCC than those with GR of < 4 mm/month. As expected, GR correlated with tumour proliferation, as determined by Ki-67 expression. CONCLUSIONS: We consider a GR of 4 mm/month as the cutoff point that distinguishes between rapid- and slow-progressing tumours and, more importantly, to identify a subset of high-risk cSCCs.

MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution. OBJECTIVES: We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours. METHODS: Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC. RESULTS: miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. CONCLUSIONS: miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC.

Epidermal growth factor receptor expression is associated with poor outcome in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers in order to recognize those CSCCs with poor prognosis. There is controversy concerning the role of epidermal growth factor receptor (EGFR) as a marker of prognosis in CSCC. In addition, EGFR-targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may be of help for some patients in predicting prognosis and guiding curative management. OBJECTIVES: To evaluate the role of EGFR as a prognostic factor in CSCC. METHODS: We evaluated clinical and histopathological features, including events of poor clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR expression by immunohistochemistry, fluorescent in situ hybridization and quantitative polymerase chain reaction. RESULTS: We detected EGFR in 85 cases (90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was associated with lymph node progression, tumour-nodes-metastasis stage progression and proliferation (Ki-67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model. CONCLUSIONS: We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC.

Agricultural activity shapes the communication and migration patterns in Senegal.

The communication and migration patterns of a country are shaped by its socioeconomic processes. The economy of Senegal is predominantly rural, as agriculture employs over 70% of the labor force. In this paper, we use mobile phone records to explore the impact of agricultural activity on the communication and mobility patterns of the inhabitants of Senegal. We find two peaks of phone calls activity emerging during the growing season. Moreover, during the harvest period, we detect an increase in the migration flows throughout the country. However, religious holidays also shape the mobility patterns of the Senegalese people. Hence, in the light of our results, agricultural activity and religious holidays are the primary drivers of mobility inside the country.

Combinación de propranolol oral y láser de colorante pulsado en el tratamiento de los hemangiomas infantiles ulcerados / Combination of pulsed dye laser and propranolol in the treatment of ulcerated infantile haemangioma

INTRODUCCIÓN: La ulceración se trata de la complicación más frecuente de los hemangiomas infantiles, produciéndose en el 15,8% de los mismos, habitualmente en el apogeo de la fase proliferativa. Existen múltiples herramientas terapéuticas para el manejo de los hemangiomas ulcerados, sin que se haya demostrado una mayor eficacia de ninguna de ellas. Presentamos nuestra experiencia en el tratamiento con láser de colorante pulsado asociado a propranolol en los hemangiomas infantiles ulcerados. MATERIAL Y MÉTODOS: Realizamos un estudio observacional retrospectivo de pacientes con hemangioma infantil ulcerado que recibieron tratamiento con láser de colorante pulsado asociado a propranolol. Estudiamos 7 pacientes; 3 con hemangiomas en la zona labial y 4 en la zona del pañal. Asimismo, revisamos una cohorte de 5 niños con hemangiomas ulcerados de similares características que solo recibieron tratamiento con propranolol, curas tópicas y vendaje oclusivo. RESULTADOS: El tamaño medio de las úlceras fue de 1cm, con un tiempo medio de evolución previo al tratamiento de 2 semanas. En todos los casos había dolor y sangrado. Tras 2 semanas de tratamiento combinado con propranolol y láser, todas las úlceras se habían curado. El dolor desaparece tras la primera sesión de láser. Los pacientes con hemangioma ulcerado en la zona labial presentaron mejor respuesta que aquellos que lo presentaban en la zona del pañal. La cohorte de pacientes tratados únicamente con propranolol, curas tópicas y vendaje oclusivo precisaron un tiempo medio para la curación de 5,2 semanas. CONCLUSIONES: Nuestros resultados evidencian que el tratamiento combinado de láser de colorante pulsado y propranolol presenta un efecto sinérgico, acelerando la curación de los hemangiomas ulcerados. Se necesitarían más estudios, con un mayor número de pacientes, para confirmar estos datos

INTRODUCTION: Ulceration is the most common complication of infantile haemangioma, with 15.8% of them usually appearing in the proliferative phase. They can be managed in several ways. We present our experience in the treatment of ulcerated haemangioma with the combination of pulsed dye laser and propranolol. MATERIAL AND METHODS: A retrospective observational study was conducted on patients with ulcerated infantile haemangioma treated with pulsed dye laser in association with propranolol. The study included 7 patients, 3 cases in labial area and 4 cases in the nappy area. A review was also performed on a historical cohort of 5 children with ulcerated haemangiomas with the same features, but treated only with propranolol, topical agents and occlusive dressings. RESULTS: The median size of the ulcer was 1.0cm, and there was a mean time of onset pre-treatment of 2 weeks. Pain and bleeding was present in all patients. After 2 weeks of combined propranolol and laser treatment, all lesions were healed. The pain disappeared after the first laser session. Patients with ulcerative haemangioma in the labial area obtained a better response than patients with haemangioma in the nappy area. The cohort of patients treated with propranolol required a mean healing time of 5.2 weeks, with the addition of an occlusive dressing with ointment. CONCLUSIONS: We believe that our results suggest that combined treatment, laser and propranolol, has synergistic effects that accelerate the healing of ulcerated haemangioma, as observed in our patients. Further studies with larger numbers of patients are needed to confirm this fact

Frequency analysis of the laser driven nonlinear dynamics of HCN.

We study the vibrational dynamics of a model for the HCN molecule in the presence of a monochromatic laser field. The variation of the structural behavior of the system as a function of the laser frequency is analyzed in detail using the smaller alignment index, frequency maps, and diffusion coefficients. It is observed that the ergodicity of the system depends on the frequency of the excitation field, especially in its transitions from and into chaos. This provides a roadmap for the possibility of bond excitation and dissociation in this molecule.

[Combination of pulsed dye laser and propranolol in the treatment of ulcerated infantile haemangioma]. / Combinación de propranolol oral y láser de colorante pulsado en el tratamiento de los hemangiomas infantiles ulcerados.

INTRODUCTION: Ulceration is the most common complication of infantile haemangioma, with 15.8% of them usually appearing in the proliferative phase. They can be managed in several ways. We present our experience in the treatment of ulcerated haemangioma with the combination of pulsed dye laser and propranolol. MATERIAL AND METHODS: A retrospective observational study was conducted on patients with ulcerated infantile haemangioma treated with pulsed dye laser in association with propranolol. The study included 7 patients, 3 cases in labial area and 4 cases in the nappy area. A review was also performed on a historical cohort of 5 children with ulcerated haemangiomas with the same features, but treated only with propranolol, topical agents and occlusive dressings. RESULTS: The median size of the ulcer was 1.0 cm, and there was a mean time of onset pre-treatment of 2 weeks. Pain and bleeding was present in all patients. After 2 weeks of combined propranolol and laser treatment, all lesions were healed. The pain disappeared after the first laser session. Patients with ulcerative haemangioma in the labial area obtained a better response than patients with haemangioma in the nappy area. The cohort of patients treated with propranolol required a mean healing time of 5.2 weeks, with the addition of an occlusive dressing with ointment. CONCLUSIONS: We believe that our results suggest that combined treatment, laser and propranolol, has synergistic effects that accelerate the healing of ulcerated haemangioma, as observed in our patients. Further studies with larger numbers of patients are needed to confirm this fact.