TET enzymes and 5hmC epigenetic mark: new key players in carcinogenesis and progression in gynecological cancers.

DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine (5mC). In general, DNA methylation in cancer is associated with the repression of the expression of tumor suppressor genes (TSG) and the demethylation with the overexpression of oncogenes. DNA methylation was considered a stable modification for a long time, but in 2009, it was reported that DNA methylation is a dynamic modification. The Ten-Eleven-Translocations (TET) enzymes include TET1, TET2, and TET3 and participate in DNA demethylation through the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC). The 5hmC oxidates to 5-formylcytosine (5fC) and 5-carboxylcitosine (5caC), which are replaced by unmodified cytosines via Thymine-DNA Glycosylase (TDG). Several studies have shown that the expression of TET proteins and 5hmC levels are deregulated in gynecological cancers, such as cervical (CC), endometrial (EC), and ovarian (OC) cancers. In addition, the molecular mechanisms involved in this deregulation have been reported, as well as their potential role as biomarkers in these types of cancers. This review shows the state-of-art TET enzymes and the 5hmC epigenetic mark in CC, EC, and OC.

Influencia de las redes de apoyo sociofamiliares en el cuidado de las personas mayores dependientes: un estudio cualitativo / Influence of social-family support networks on the care of dependent older people: a qualitative study

Fundamentos: Las redes de apoyo sociofamiliares son necesarias para el cuidado de las personas dependientes. El objetivo de este estudio fue explorar los tipos de apoyo que se dan en las Redes de Apoyo Sociofamiliares (RASF) de las personas dependientes mayores del Distrito Sanitario Aljarafe-Sevilla Norte (España) desde una perspectiva de género. Métodos: Se realizó un estudio cualitativo de corte biográfico, basado en la realización de entrevistas semiestructuradas. El tamaño de la muestra atendió al criterio de saturación teórica. Participaron en el estudio un total de veinticuatro personas, quince mujeres y nueve hombres. Para el análisis cualitativo del contenido y del discurso de las personas entrevistadas se siguió la Teoría Fundamentada. Resultados: Emergieron cuatro categorías correspondientes a los tipos de apoyo prestados: apoyo cognitivo, material, instrumental y emocional. Estas categorías correspondían a los prototipos que las personas cuidadoras y pacientes construían a través de las ideas y conceptos que tenían sobre el cuidado a personas dependientes. Los distintos tipos de apoyo prestados disminuían el malestar de todos los componentes de las RASF. Se evidenciaron diferencias en los discursos entre hombres y mujeres. Conclusiones: Cuidar continúa siendo una actividad que suelen realizar las mujeres. Los tipos de apoyos analizados demuestran que la existencia de una red es una garantía de cuidados y que el empleo de las RASF reduce la sobrecarga de la persona cuidadora al estar compensadas con los otros miembros de la red. Por tanto, las redes son un factor de protección de la salud para las personas cuidadoras familiares.(AU)

Background: Socio-family support networks (SFSN) are necessary for the care of dependent people. This study aimed to explore the types of support provided in the SFSN for dependent older people in the Aljarafe Health District-Sevilla Norte (Spain) from a gender perspective. Methods: A qualitative biographical study was carried out, based on semi-structured interviews. The sample size met the theoretical saturation criterion. A total of twenty-four people participated in the study, fifteen women and nine men. For the qualitative analysis of the content and discourse of the people interviewed, Grounded Theory was followed. Results: Four categories emerged corresponding to thnal support. These categories corresponded to the prototypes that caregivers and patients built through the ideas and concepts they had about caring for dependent people. The different types of support provided reduced the discomfort of all members of the SFSN. Differences were evident in the speeches between men and women. Conclusions: Caring continues to be an activity that women usually do. The types of support analyzed show that the existence of a network is a guarantee of care and the use of SFSN reduces the overload of the caregiver by being compensated with the other members of the network. Therefore, networks are a health protection factor for family caregivers.(AU)

Incidence of adverse drug reactions in COVID-19 hospitalised patients through the minimum basic data set / Incidencia de reacciones adversas a medicamentos en pacientes hospitalizados por COVID-19 a través del conjunto mínimo básico de datos

Background: At the beginning of the COVID-19 pandemic many drugs were used with an uncertain benefit/risk profile that needed to be evaluated. The goal of this study was to analyse the incidence of adverse drug reactions (ADRs) and describe the drugs used in COVID-19 hospitalised patients at the beginning of the COVID-19 pandemic through the minimum basic data set (MBDS). Methods: Retrospective observational study that included hospitalised patients with COVID-19 at our centre between March and May 2020 who had ADRs coded in discharge/death medical reports according to the International Classification of Diseases (ICD-10). Those patients with ADRs ascribed to COVID therapy were selected and the causal relationship was evaluated using the Naranjo algorithm. Descriptive statistical analysis was used. Results: We identified 141 ADRs in 110 cases of hospitalisation due to COVID-19 that entailed an incidence of 9.66% (141/1459), CI95% 8.25-11.29. From the ADRs analysed, 60.3% (85/141) were ascribed to COVID therapy. Lopinavir/ritonavir represented 38.8% (33/85) of ADRs, glucocorticoids 23.5% (20/85) and hydroxychloroquine 9.4% (8/85). Out of the ADRs, 31.8% (27/85) were gastrointestinal disorders (probable lopinavir/ritonavir), 27.0% (23/85) blood glucose disorders (probable glucocorticoid) and 17.6% (15/85) hypertransaminasaemia (probable azithromycin, possible lopinavir/ritonavir, possible hydroxychloroquine, possible interferon). Regarding intensity, 64.7% (55/85) were mild cases, 29.4% (25/85) moderate and 5.9% (5/85) severe. The percentage of ADRs that did not require intervention were 24.7% (21/85), 32.9% (28/85) required pharmacological treatment, 40.0% (34/85) suspension of the drug, 1.2% (1/85) close monitoring and 1.2% (1/85) dose reduction. Conclusions: The incidence of ADR in COVID population that required admission at the beginning of the pandemic seems to be higher than in the general population. The MBDS proves to be a useful tool to trace ADRs. (AU)

Introducción: La llegada de la pandemia de COVID-19 supuso la utilización de muchos fármacos con un perfil de riesgo/beneficio incierto que debe ser evaluado. El objetivo de este estudio fue analizar la incidencia de reacciones adversas a medicamentos (RAM) y describir los medicamentos utilizados en pacientes hospitalizados por COVID-19 al comienzo de la pandemia a través del conjunto mínimo básico de datos (CMBD). Materiales y métodos: Estudio observacional retrospectivo que incluyó pacientes hospitalizados por COVID-19 en nuestro centro entre marzo y mayo de 2020 que presentaban RAM codificadas en los informes médicos de alta/exitus según la Clasificación Internacional de Enfermedades (CIE-10). Se seleccionaron los pacientes con RAM atribuidas a la terapia COVID-19 y se evaluó la relación causal mediante el algoritmo de Naranjo. Se realizó un análisis estadístico descriptivo. Resultados: Identificamos 141 RAM en 110 casos de hospitalización por COVID-19 lo que supone una incidencia del 9,66% (141/1459), IC95% 8,25-11,29. De las RAM analizadas el 60,3% (85/141) se atribuyeron a la terapia COVID. Lopinavir/ritonavir representó el 38,8% (33/85) de las RAM, los glucocorticoides el 23,5% (20/85) y la hidroxicloroquina el 9,4% (8/85). De todas las RAM, el 31,8% (27/85) fueron trastornos gastrointestinales (probable lopinavir /ritonavir), el 27,0% (23/85) trastornos de la glucemia (probable glucocorticoide) y el 17,6% (15/85) hipertransaminasemia (probable azitromicina, posible lopinavir /ritonavir, posible hidroxicloroquina, posible interferón). En cuanto a la intensidad, el 64,7% (55/85) de las RAM fueron casos leves, el 29,4% (25/85) moderados y el 5,9% (5/85) graves. El porcentaje de RAM que no requirió intervención fue 24,7% (21/85), 32,9% (28/85) requirió tratamiento farmacológico, 40,0% (34/85) suspensión del fármaco, 1,2% (1/85) seguimiento estrecho y 1,2% (1/85) reducción de dosis... (AU)

EMMPRIN is an emerging protein capable of regulating cancer hallmarks.

EMMPRIN, also known as Basigin or CD147, is a transmembrane glycoprotein member of the immunoglobulin superfamily. It is expressed basally in cells that regulate physiological processes of the cardiovascular, nervous, and immune systems. However, EMMPRIN is also capable of interacting with different proteins, like VEGFR, SMAD4, Integrin, MCT, CyPA, GLUT1, CAIV, Annexin II, Cav-1, CAML, etc., and regulating signaling pathways that stimulate the cell processes of proliferation, apoptosis, metabolism, adhesion, invasion, migration, metastasis, tumor immune response, and angiogenesis processes, which favors the development of different types of cancer. EMMPRIN is the first protein reported that favors cancer development due to its ability to interact with extracellular, intracellular, and membrane proteins. In conclusion, EMMPRIN regulates several proteins associated with the development of tumor processes. Therefore, blocking the expression of EMMPRIN can be a therapeutic target, and the analysis of its expression can be used as an important biomarker in cancer.

The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19.

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥4 was found to be the best cutoff point for predicting respiratory failure.

Utilidad de las escalas de sepsis para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 fuera de las Unidades de Cuidados Intensivos / The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19

El presente estudio retrospectivo observacional tiene como objetivo analizar la utilidad de las escalas SOFA (Sequential Organ Failure Assessment), qSOFA (Quick SOFA), NEWS (National Early Warning Score ) y Quick NEWS para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 atendidos fuera de la Unidad de Cuidados Intensivos (UCI). Se incluyeron 237 adultos con COVID-19 hospitalizados seguidos durante un mes o hasta su fallecimiento. El fallo respiratorio se definió como un cociente PaO2/FiO2 ≤ 200 mmHg o la necesidad de ventilación mecánica. Setenta y siete pacientes (32,5%) desarrollaron fallo ventilatorio; 29 (12%) precisaron ingreso en UCI, y 49 fallecieron (20,7%). La discriminación del fallo ventilatorio fue algo mayor con la puntuación NEWS, seguida de la SOFA. En cuanto a la mortalidad, la puntuación SOFA fue más exacta que las otras escalas. En conclusión, las escalas de sepsis son útiles para predecir el fallo respiratorio y la muerte en COVID-19. Una puntuación ≥ 4 en la escala NEWS sería el mejor punto de corte para predecir fallo respiratorio (AU)

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure (AU)

[The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19]. / Utilidad de las escalas de sepsis para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 fuera de las Unidades de Cuidados Intensivos.

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure.

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Continuous intestinal infusion of levodopa-carbidopa in patients with advanced Parkinson's disease in Spain: Subanalysis by autonomous community. / Uso de la infusión intestinal continua de levodopa-carbidopa en pacientes con enfermedad de Parkinson avanzada en España. Subanálisis por comunidades autónomas.

OBJECTIVES: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. METHODS: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients' clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation. RESULTS: Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of≥ 4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (> 24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2 CAs). CONCLUSIONS: This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients' baseline characteristics, the availability of multidisciplinary teams, and clinical experience.

Use of coumarins as complementary medicine with an integrative approach against cervical cancer: background and mechanisms of action.

Cervical cancer is characterized by the cellular transformation caused by Human Papillomavirus (HPV), favoring cell proliferation, migration, invasion, and metastasis. Cervical cancer is conventionally treated with radiation therapy, and chemotherapy focused on the destruction of tumor cells. However, chemoresistance and low selectivity between tumor and non-tumor cells have been reported, causing side effects in patients. Metabolites of natural origin have shown selectivity against tumor cells, suggesting their use for reducing the side effects caused by drugs used in conventional therapy. Among these compounds, several natural coumarins stand out, such as auraptene, scopoletin, osthole, and praeruptorin, of which antiproliferative, anti-migratory, and anti-invasive activity have been reported. Auraptene, scopoletin, osthole, and praeruptorin show a cytotoxic or antiproliferative effect on cervical tumor cells, arresting the cell cycle by inducing the overexpression of negative regulators of the cell cycle, or inducing cell death by increasing the expression of pro-apoptotic proteins and decreasing that of anti-apoptotic proteins. On the other hand, auraptene, scopoletin, and praeruptorin inhibit the capacity for migration, invasion, and metastasis of cervical tumor cells, mainly by inhibiting the expression and activity of matrix metalloproteinase-2 and -9. The PI3K/Akt signal pathway appears to be central to the anti-tumor activity of the coumarins analyzed in this review. In addition, auraptene, osthole, and praeruptorin are useful in sensitizing tumor cells to radiotherapy or chemotherapeutic molecules, such as FOLFOX, cisplatin, or DOX. Coumarins offer an excellent possibility for developing new drugs as complementary medicine with an integrative approach against cervical cancer.

Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson's Disease.

INTRODUCTION: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. METHODS: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson's disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. RESULTS: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015-1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009-1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. CONCLUSION: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo / Clinical experience in the treatment of motor fluctuations in Parkinsons disease. Delphi consensus of a group of experts in movement disorders

INTRODUCCIÓN: Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. DESARROLLO: Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. CONCLUSIÓN: El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motora

INTRODUCTION. Motor fluctuations are one of the most common complications of Parkinsons disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT. Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION. The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations

[Clinical experience in the treatment of motor fluctuations in Parkinson's disease. Delphi consensus of a group of experts in movement disorders]. / Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.

INTRODUCTION: Motor fluctuations are one of the most common complications of Parkinson's disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT: Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION: The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations.

TITLE: Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.Introducción. Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. Desarrollo. Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. Conclusión. El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motoras.

Changes of resistance rates in Pseudomonas aeruginosa strains are unrelated to antimicrobial consumption in ICU populations with invasive device-related infection / Los cambios en la resistencia de cepas de Pseudomonas aeruginosa identificadas en infecciones relacionadas con dispositivos invasores no se relacionan con el consumo de antibióticos en la UCI

OBJECTIVE: To evaluate the relationship between antipseudomonal antibiotic consumption and each individual drug resistance rate in Pseudomonas aeruginosa strains causing ICU acquired invasive device-related infections (IDRI). DESIGN: A post hoc analysis was made of the data collected prospectively from the ENVIN-HELICS registry. SETTING: Intensive Care Units participating in the ENVIN-UCI registry between the years 2007 and 2016 (3-month registry each year). PATIENTS: Patients admitted for over 24h. MAIN VARIABLES: Annual linear and nonlinear trends of resistance rates of P. aeruginosa strains identified in IDRI and days of treatment of each antipseudomonal antibiotic family per 1000 occupied ICU bed days (DOT) were calculated. RESULTS: A total of 15,095 episodes of IDRI were diagnosed in 11,652 patients (6.2% out of a total of 187,100). Pseudomonas aeruginosa was identified in 2095 (13.6%) of 15,432 pathogens causing IDRI. Resistance increased significantly over the study period for piperacillin-tazobactam (P<0.001), imipenem (P=0.016), meropenem (P=0.004), ceftazidime (P=0.005) and cefepime (P=0.015), while variations in resistance rates for amikacin, ciprofloxacin, levofloxacin and colistin proved nonsignificant. A significant DOT decrease was observed for aminoglycosides (P<0.001), cephalosporins (P<0.001), quinolones (P<0.001) and carbapenems (P<0.001). CONCLUSIONS: No significant association was observed between consumption of each antipseudomonal antibiotic family and the respective resistance rates for P. aeruginosa strains identified in IDRI

OBJETIVO: Evaluar la relación entre el consumo de antibióticos antipseudomonales y la tasa de resistencia de cada fármaco individual en cepas de Pseudomonas aeruginosa aisladas en infecciones relacionadas con dispositivos invasivos (IDRI, por sus siglas en inglés) adquiridas en la unidad de cuidados intensivos (UCI). DISEÑO: Análisis post-hoc de los datos recopilados prospectivamente del registro ENVIN-HELICS. Ámbito: Las UCI que participaron en el registro ENVIN-UCI entre los años 2007-2016 (registro de 3 meses cada año). PACIENTES: Pacientes ingresados >24h. VARIABLES PRINCIPALES: Se calcularon las tendencias anuales lineales y no lineales de las tasas de resistencia de las cepas de P. aeruginosa identificadas en IDRI y los días de tratamiento de cada familia de antibióticos antipseudomonales por 1.000 días de cama ocupada en la UCI (DOT). RESULTADOS: Se diagnosticaron 15.095 episodios de IDRI en 11.652 pacientes (6,2% de 187.100). Se identificó P. aeruginosa en 2.095 (13,6%) de 15.432 patógenos que causaron IDRI. La resistencia aumentó significativamente durante el período de estudio para piperacilina-tazobactam (p < 0,001), imipenem (p = 0,016), meropenem (p = 0,004), ceftazidima (p = 0,005) y cefepima (p = 0,015), mientras que las variaciones en las tasas de resistencia de amikacina, ciprofloxacina, levofloxacina y colistina no fueron significativas. Se observó una disminución significativa de la DOT para aminoglucósidos (p < 0,001), cefalosporinas (p < 0,001), quinolonas (p < 0,001) y carbapenems (p < 0,001). CONCLUSIONES: No se encontró asociación significativa del consumo de cada familia de antibióticos antipseudomonales con sus respectivas tasas de resistencia para las cepas de P. aeruginosa identificadas en IDRI

Long non-coding RNAs as new players in cervical carcinogenesis: an update.

Cervical cancer (CC) is the fourth most common cancer in women worldwide. Therefore, it is very important to understand cervical carcinogenesis, as well as the molecular mechanisms and signaling pathways involved in this process, in order to develop new strategies that contribute to diagnosis, prognosis and treatment of cervical cancer. Infection by high risk-human papillomavirus (HR-HPV) is a key event in cervical carcinogenesis, as well as, other factors, such as sociodemographics, lifestyle, sexual behavior, etc. In recent years, it has been shown that long non-coding RNA (lncRNA) are involved in CC and can be classified into tumor promoters or suppressors. Currently, several studies have analyzed the molecular mechanisms of some lncRNA in CC that might be acting, such as 1) competing endogenous RNAs (ceRNAs), 2) activators of signaling pathways, and 3) transcriptional regulators of genes. In this review, we summarized the more recent information on lncRNA and their role in the development of CC.

Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression.

BACKGROUND: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. MATERIAL AND METHODS: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. RESULTS: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ±â€¯12.8 vs 11.6 ±â€¯10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ±â€¯0.5 vs 4 ±â€¯0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ±â€¯32 vs 29.1 ±â€¯25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. CONCLUSIONS: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.

Non-motor symptom burden is strongly correlated to motor complications in patients with Parkinson's disease.

BACKGROUND AND PURPOSE: The objective of this study was to analyze the relationship between motor complications and non-motor symptom (NMS) burden in a population of patients with Parkinson's disease (PD) and also in a subgroup of patients with early PD. METHODS: Patients with PD from the COPPADIS cohort were included in this cross-sectional study. NMS burden was defined according to the Non-Motor Symptoms Scale (NMSS) total score. Unified Parkinson's Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD. RESULTS: Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS-III score and levodopa equivalent daily dose, UPDRS-IV score was significantly related to a higher NMSS total score (ß = 0.27; 95% confidence intervals, 2.81-5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17-1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained. CONCLUSIONS: Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.

Changes of resistance rates in Pseudomonas aeruginosa strains are unrelated to antimicrobial consumption in ICU populations with invasive device-related infection.

OBJECTIVE: To evaluate the relationship between antipseudomonal antibiotic consumption and each individual drug resistance rate in Pseudomonas aeruginosa strains causing ICU acquired invasive device-related infections (IDRI). DESIGN: A post hoc analysis was made of the data collected prospectively from the ENVIN-HELICS registry. SETTING: Intensive Care Units participating in the ENVIN-UCI registry between the years 2007 and 2016 (3-month registry each year). PATIENTS: Patients admitted for over 24h. MAIN VARIABLES: Annual linear and nonlinear trends of resistance rates of P. aeruginosa strains identified in IDRI and days of treatment of each antipseudomonal antibiotic family per 1000 occupied ICU bed days (DOT) were calculated. RESULTS: A total of 15,095 episodes of IDRI were diagnosed in 11,652 patients (6.2% out of a total of 187,100). Pseudomonas aeruginosa was identified in 2095 (13.6%) of 15,432 pathogens causing IDRI. Resistance increased significantly over the study period for piperacillin-tazobactam (P<0.001), imipenem (P=0.016), meropenem (P=0.004), ceftazidime (P=0.005) and cefepime (P=0.015), while variations in resistance rates for amikacin, ciprofloxacin, levofloxacin and colistin proved nonsignificant. A significant DOT decrease was observed for aminoglycosides (P<0.001), cephalosporins (P<0.001), quinolones (P<0.001) and carbapenems (P<0.001). CONCLUSIONS: No significant association was observed between consumption of each antipseudomonal antibiotic family and the respective resistance rates for P. aeruginosa strains identified in IDRI.

Adaptación en las UCI de las recomendaciones de los proyectos ZERO durante la pandemia por SARS-CoV-2 / No disponible

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