MUC16 mutation is associated with tumor grade, clinical features, and prognosis in glioma patients.

MUC16 is a member of the attached mucin family that encodes cancer antigen 125 (CA-125), but the association of MUC16 status with grade and subtypes of glioma patients has not yet been established. Data for MUC16 mRNA expression in 37 different cancer types were considered, and genomic data from the Cancer Genome Atlas (TCGA) from 1051 low-grade glioma (LGG) patients and 833 glioblastoma (GBM) patients were analyzed. LGG and GBM has low expression of MUC16, but it is frequently mutated in GBM. Kaplan-Meier survival analysis, glioma subtypes, methylation, and isocitrate dehydrogenase (IDH1) status were all performed. We found that mutated-MUC16 in LGG patients is associated with better prognosis considering overall survival (OS), IDH1, methylation, 1p/19q, and 10q status. Conversely, MUC16 mutation were related with worse prognosis in GBM patients upon analyzing those same parameters. Therefore, MUC16 mutations may assist in glioma diagnosis and prognosis and should be further studied in this tumor type.

Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain. METHODS: We gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017. RESULTS: The study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%. The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P=.008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P=.897). CONCLUSIONS: The diagnostic delay in ALS in Spain is similar to that of neighbouring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centres may help to reduce diagnostic delay.

Análisis del trayecto y retraso diagnóstico de los pacientes con esclerosis lateral amiotrófica en la Comunidad Valenciana / Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community

Introducción: La esclerosis lateral amiotrófica (ELA) es una enfermedad insidiosa y clínicamente heterogénea, lo que resulta en un retraso diagnóstico de unos 12 meses. En España el trayecto diagnóstico no ha sido analizado.MétodosSe recogieron variables relativas al trayecto y retraso diagnóstico de pacientes diagnosticados de ELA entre octubre del 2013 y julio del 2017.ResultadosSe incluyó a 143 pacientes con ELA (57% varones, 68% de inicio espinal). El 86% de ellos fueron estudiados en centros públicos y un 14% en privados. El retraso diagnóstico medio fue de 13,1 meses (mediana 11.7). El paciente tardó de media 7,9 meses en llegar al neurólogo y este, 5,2 meses más en diagnosticarlo. En la mitad de los pacientes se realizaron pruebas innecesarias y más de un estudio electrofisiológico para llegar al diagnóstico. El retraso diagnóstico fue mayor en los casos espinales (p = 0,008), atribuible a los pacientes cuyos síntomas se iniciaron en miembros inferiores, pero sin diferencias entre el sistema público y privado (p = 0,897).ConclusionesEl retraso diagnóstico de la ELA en nuestro medio es similar al de países de nuestro entorno y parece determinado por factores propios de la enfermedad e independiente del sistema sanitario. Las formas de inicio en miembros inferiores constituyen el mayor reto. Los errores diagnósticos del neurólogo son frecuentes y en parte atribuibles a una mala orientación o interpretación del estudio electrofisiológico. La formación específica del neurólogo y neurofisiólogo general y la derivación precoz a centros de referencia podrían ayudar a reducir la demora. (AU)

Introduction: Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain.MethodsWe gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017.ResultsThe study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%.The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P = .008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P = .897).ConclusionsThe diagnostic delay in ALS in Spain is similar to that of neighboring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centers may help to reduce diagnostic delay. (AU)

Synergistic activation of AMPK prevents from polyglutamine-induced toxicity in Caenorhabditis elegans.

Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g., metformin, have been proposed as therapeutic solutions. In this work, we show that metformin, together with salicylate, can synergistically reduce the number of aggregates produced after polyQ expression in Caenorhabditis elegans. Moreover, we demonstrate that incubation polyQ-stressed worms with low doses of both chemicals restores neuronal functionality. Both substances are pleitotropic and may activate a range of different targets. However, we demonstrate in this report that the beneficial effect induced by the combination of these drugs depends entirely on the catalytic action of AMPK, since loss of function mutants of aak-2/AMPKα2 do not respond to the treatment. To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKß1. In addition, we used an RNAi strategy to silence the expression of the second AMPKß subunit in worms, namely aakb-2/AMPKß2. In this work, we demonstrated that both regulatory subunits of AMPK are modulators of protein homeostasis. Interestingly, only aakb-2/AMPKß2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation. Finally, we showed that autophagy acts downstream of metformin/salicylate-related AMPK activation to promote healthy protein homeostasis in worms.

Impact of real-time, dose-escalated permanent seed implant brachytherapy in intermediate-risk prostate cancer.

PURPOSE: To retrospectively evaluate biochemical control and toxicity in patients who underwent 125I seed brachytherapy (BT) for intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: Between January 2004-December 2014, 395 patients with intermediate-risk PCa underwent 125I BT. Of these, 117 underwent preoperative planning (PP; 145 Gy) and 278 real-time intraoperative preplanning (IoP; 160 Gy). All patients were followed for ≥ 6 months (> 5 years in 48% of patients and > 7 years in 13%). Median follow-up was 59 months. RESULTS: Biochemical relapse-free survival (BRFS) rates at 5 and 8 years were, respectively, 91.7% and 82.1%. By treatment group, the corresponding BRFS rates were 93.5% and 90% for IoP and 89% and 76.8% for PP. The maximum dose to the urethra remained unchanged (217 Gy) despite the dose escalation (from 145 to 160 Gy), without any significant increase in treatment-related toxicity (p = 0.13). Overall toxicity outcomes in the series were excellent, with only 3 cases (0.76%) of grade 3 genitourinary toxicity. CONCLUSION: The real-time intraoperative planning technique at 160 Gy yields better biochemical controls than the preoperative planning technique at 145 Gy. Dose escalation did not increase urinary toxicity. The excellent results obtained with the IoP BT technique support its use as the first treatment option in this patient population.

Valoración de la grasa hepática y pancreática como biomarcadores de imagen en el síndrome metabólico / Hepatic and pancreatic fat as imaging biomarkers of metabolic syndrome

OBJETIVO: Valorar objetivamente la afectación hepática y pancreática en el síndrome metabólico mediante biomarcadores de resonancia magnética (RM). MATERIAL Y MÉTODOS: Serie retrospectiva inicial de 407 pacientes con diagnóstico de síndrome metabólico, estudiados con RM en un único centro durante 2 años. Se excluyeron 154 pacientes por falta de datos clínico-analíticos, alteraciones pancreáticas o inadecuada calidad de la RM. Para la medición de la grasa hepática y pancreática se utilizaron las imágenes con desplazamiento químico (en fase y fase opuesta), con medidas por regiones de interés de la fracción grasa (%) en el páncreas (FGP) e hígado (FGH). La asociación entre las variables clínico-analíticas seleccionadas y la fracción grasa se evaluó mediante modelos de regresión beta. RESULTADOS: Se incluyeron finalmente 253 pacientes. La FGH fue del 4,9% y la FGP del 7,9%. La FGH no presentó ninguna asociación estadística con las variables clínico-analíticas. Sin embargo, la FGP se asoció positivamente con la edad (odds ratio [OR]=1,025, p <0,001) y la glucosa basal (OR=1,005, p <0,001). Se observó que los pacientes con diabetes presentaban valores más altos de FGP (OR=2,64, p = 0,038). La FGP y la FGH estaban relacionadas de manera estadísticamente positiva (OR=69,44, p <0,001). CONCLUSIONES: La esteatosis pancreática puede considerarse un marcador del síndrome metabólico y la diabetes. La RM cuantitativa permite el diagnóstico y la gradación de pacientes con páncreas graso mediante técnicas sencillas de desplazamiento químico

OBJECTIVE: To objectively evaluate hepatic and pancreatic involvement in metabolic syndrome through magnetic resonance imaging (MRI) biomarkers. MATERIAL AND METHODS: From an initial retrospective sample of 407 patients diagnosed with metabolic syndrome studied by MRI in a single center during a 2-year period, 154 were excluded because of a lack of clinical and/or laboratory data, pancreatic abnormalities, or inadequate quality of MRI studies. To measure hepatic and pancreatic fat, we used chemical shift imaging (in-phase and out-of-phase), measuring the fat fraction (%) in regions of interest in the pancreas and liver. Associations between the fat fraction and selected clinical and laboratory variables were assessed with beta regression models. RESULTS: In the end, 253 patients were included. The hepatic fat fraction was 4.9% and the pancreatic fat fraction was 7.9%. We found no significant associations between the hepatic fat fraction and any of the clinical or laboratory variables. However, the pancreatic fat fraction was positively associated with age (OR=1.025, p < 0.001) and baseline glucose (OR=1.005, p < 0.001). Patients with diabetes had higher values of pancreatic fat fraction (OR=2.64, p = 0.038). Pancreatic fat fraction and hepatic fat fraction were positively associated (OR=69.44, p < 0.001). CONCLUSIONS: Pancreatic steatosis can be considered a marker of metabolic syndrome and diabetes. Quantitative MRI enables the diagnosis and grading of fatty pancreas through simple chemical shift techniques

Hepatic and pancreatic fat as imaging biomarkers of metabolic syndrome. / Valoración de la grasa hepática y pancreática como biomarcadores de imagen en el síndrome metabólico.

OBJECTIVE: To objectively evaluate hepatic and pancreatic involvement in metabolic syndrome through magnetic resonance imaging (MRI) biomarkers. MATERIAL AND METHODS: From an initial retrospective sample of 407 patients diagnosed with metabolic syndrome studied by MRI in a single center during a 2-year period, 154 were excluded because of a lack of clinical and/or laboratory data, pancreatic abnormalities, or inadequate quality of MRI studies. To measure hepatic and pancreatic fat, we used chemical shift imaging (in-phase and out-of-phase), measuring the fat fraction (%) in regions of interest in the pancreas and liver. Associations between the fat fraction and selected clinical and laboratory variables were assessed with beta regression models. RESULTS: In the end, 253 patients were included. The hepatic fat fraction was 4.9% and the pancreatic fat fraction was 7.9%. We found no significant associations between the hepatic fat fraction and any of the clinical or laboratory variables. However, the pancreatic fat fraction was positively associated with age (OR=1.025, p<0.001) and baseline glucose (OR=1.005, p<0.001). Patients with diabetes had higher values of pancreatic fat fraction (OR=2.64, p=0.038). Pancreatic fat fraction and hepatic fat fraction were positively associated (OR=69.44, p<0.001). CONCLUSIONS: Pancreatic steatosis can be considered a marker of metabolic syndrome and diabetes. Quantitative MRI enables the diagnosis and grading of fatty pancreas through simple chemical shift techniques.

Personality disorders, addictions and psychopathy as predictors of criminal behaviour in a prison sample.

AIMS: Disturbances in personality and addictions are associated with an increased risk of committing crimes and therefore of being imprisoned. In this study, the relationship between these factors is analyzed through a sample of inmates in the Prison of Pereiro de Aguiar, Ourense. MATERIAL AND METHOD: 204 inmates participated in this transversal simple blind design study. The following variables were analyzed: presence of personality disorders and psychopathy, history of addictive psychoactive substance use, criminal history and socio-demographic variables. RESULTS: 101 (49.5%) inmates received a diagnosis of personality disorder, the most frequent being: narcissistic, 43 (21.08%); antisocial, 38 (18.63%); and paranoid, 29 (14.22%). The presence of any personality disorder was associated with an increase in the risk of committing crimes, especially violence and crimes against property. The most frequent personality disorders were associated with higher scores in the psychopathy assessment tools. Higher scores in the Psychopathy Checklist Reviewed (PCL-R) correlated with an increased risk of committing the following crimes: violent, against public health, against property and disorderly conduct. The consumption of addictive psychoactive substances was associated with the commission of crimes against property. Methadone stood out for its protective role against the commission of violent crimes. DISCUSSION: This sample shows that inmates have a higher prevalence of personality disorders, psychopathy and consumption of addictive psychoactive substances. These three variables significantly increased the risk of committing crimes.

Trastornos de la personalidad, adicciones y psicopatía como predictores de la conducta delictiva en una muestra penitenciaria / Personality disorders, addictions and psychopathy as predictors of criminal behaviour in a prison sample

Objetivo: Las perturbaciones de la personalidad y las adicciones se asocian con un aumento del riesgo de cometer delitos y, con ello, de ingresar en prisión. En este estudio se analiza la relación entre estos factores con una muestra de internos en el Centro Penitenciario de Pereiro de Aguiar de Ourense. Material y método: 204 internos participaron en este estudio transversal retrospectivo con un diseño ciego simple. Se analizaron las siguientes variables: trastornos de la personalidad y psicopatía, consumo de sustancias, historial delictivo y variables sociodemográficas. Resultados: 101 (49,5%) internos recibieron un diagnóstico de trastorno de la personalidad. Los más frecuentes fueron: narcisista, 43 (21,08%); antisocial, 38 (18,63%); y paranoide, 29 (14,22%). La presencia de cualquier trastorno de la personalidad se asoció a un aumento en el riesgo de cometer delitos, especialmente delitos violentos y contra la propiedad. Los trastornos de la personalidad más frecuentes se asociaron a puntuaciones más elevadas en los instrumentos de valoración de la psicopatía. Puntuaciones elevadas en la escala de evaluación de psicopatía de Hare revisada (Psychopathy Checklist Reviewed, PCL-R) se correlacionaron con un mayor riesgo de cometer delitos violentos, contra la salud pública, contra la propiedad y de alteración del orden público. El consumo de sustancias adictivas se asoció a la comisión de delitos contra la propiedad. La metadona destacó por su papel protector frente a la comisión de delitos violentos. Discusión: En esta muestra, se objetiva que los internos presentan una mayor prevalencia de trastornos de la personalidad, psicopatía y consumo de sustancias adictivas. Estas tres variables aumentaron de forma significativa el riesgo de cometer delitos

Aims: Disturbances in personality and addictions are associated with an increased risk of committing crimes and therefore of being imprisoned. In this study, the relationship between these factors is analyzed through a sample of inmates in the Prison of Pereiro de Aguiar, Ourense. Material and method: 204 inmates participated in this transversal simple blind design study. The following variables were analyzed: presence of personality disorders and psychopathy, history of addictive psychoactive substance use, criminal history and socio-demographic variables. Results: 101 (49.5%) inmates received a diagnosis of personality disorder, the most frequent being: narcissistic, 43 (21.08%); antisocial, 38 (18.63%); and paranoid, 29 (14.22%). The presence of any personality disorder was associated with an increase in the risk of committing crimes, especially violence and crimes against property. The most frequent personality disorders were associated with higher scores in the psychopathy assessment tools. Higher scores in the Psychopathy Checklist Reviewed (PCL-R) correlated with an increased risk of committing the following crimes: violent, against public health, against property and disorderly conduct. The consumption of addictive psychoactive substances was associated with the commission of crimes against property. Methadone stood out for its protective role against the commission of violent crimes. Discussion: This sample shows that inmates have a higher prevalence of personality disorders, psychopathy and consumption of addictive psychoactive substances. These three variables significantly increased the risk of committing crimes

New insights into the pathophysiology of fasciculations in amyotrophic lateral sclerosis: An ultrasound study.

OBJECTIVE: To describe the fasciculation pattern in ALS and to analyse its clinical and pathophysiological significance. METHODS: Ultrasound of 19 muscles was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The number of fasciculations was recorded in each muscle and the muscle thickness and strength were additionally measured in limb muscles. A subgroup of patients were electromyographically assessed. RESULTS: US was performed in 835 muscles and EMG was available in 263 muscles. US detected fasciculations more frequently than EMG. Fasciculations were widespread, especially in upper limbs onset patients and in the cervical region. Fasciculations' number inversely associated with ALSFR-R and body mass index (BMI) and directly with BMI loss and upper motor neuron (UMN) impairment. Our statistical model suggest that fasciculations increase with the initial lower motor neuron (LMN) degeneration, reach their peak when the muscle became mildly to moderately weak, decreasing afterwards with increasing muscle weakness and atrophy. CONCLUSIONS: Our study suggests that both UMN and LMN degeneration trigger fasciculations causing BMI loss. The degree of LMN impairment could account for differences in fasciculations' rates within and between muscles. SIGNIFICANCE: In ALS, fasciculations could explain the link between hyperexcitability and BMI loss.

Exploratory analysis for the implementation of antineoplastic logarithmic dose banding.

Background Dose banding (DB) is a strategy to rationalise antineoplastic production at Hospital Pharmacy Aseptic Compounding Units (ACUs) and to reduce patient's waiting time. DB allows for optimizing workflows and workloads, facilitating adoption of new technologies, and increasing safety, quality and efficiency of the compounding process. Objective To evaluate the potential impact of implementation of Logarithmic DB and to identify antineoplastic agents and preparations that fulfil criteria published and establish the number and standard doses that could be compounded in advance at the ACU. Setting University and Polytechnic third level general hospital. Method Retrospective observational study (December 2015-May 2016). Antineoplastic dose production was analysed. Investigational drugs were excluded. Three criteria were applied following bibliography reviewed to select candidates to be compounded at our ACU as standardised using logarithmic DB: (a) Antineoplastic preparations > 250 per year; (b) psychochemical stability in optimal storage conditions at least 14 days; (c) maximum five logarithmic standardised doses that include at least 60% of all individualised doses compounded for a given drug. Main outcome measure Number of antineoplastic agents, preparations and logarithmic standard doses candidates to DB. Results 15,436 antineoplastic individualised doses corresponding to 69 antineoplastic agents were analysed. At our institution applying selection criteria, 19 (27%) antineoplastic drugs (3 monoclonal antibodies, 16 cytotoxic) were potential candidates to DB. 6285 (40%) of compounded individualised dose preparations could be prepared in 84 logarithmic standard doses in advance. Conclusion Dose banding implementations could contribute to rationalise antineoplastic production and increase the ACUs compounding capacity.

Incidencia y resultados clínicos de las distintas formas neovasculares de degeneración macular asociada a la edad en Valencia (España) / Incidence and clinical outcomes of the different neovascular forms of age-related macular degeneration in Valencia (Spain)

OBJETIVO: Analizar la incidencia y los resultados visuales de cada uno de los subtipos de lesión neovascular en pacientes con degeneración macular asociada la edad (DMAE). MATERIAL Y MÉTODOS: Revisión retrospectiva de pacientes con DMAE neovascular tratados en el Hospital Universitario y Politécnico la Fe de Valencia por un mismo retinólogo (RGP) desde diciembre de 2012 hasta julio del 2015. Se registraron las formas anatómicas del complejo neovascular, así como el número de tratamientos intravítreos administrados y el cambio de visión obtenido con este. RESULTADOS: Fueron incluidos 174 ojos de 156 pacientes con una edad media de 79,9 años y un seguimiento de al menos 4 meses. El 40,8% presentaban neovascularización coroidea (NVC) tipo 1; el 12%, tipo 2; el 31%, tipo 3; el 14,4% presentaban formas mixtas y el 1,7%, vasculopatía polipoidea. La agudeza visual inicial media era de 0,32 y de 0,38 a los 24 meses, habiendo recibido una media de 9,3 inyecciones. Las formas neovasculares tipo 2, 3 y mixtas mostraron un resultado visual significativamente inferior a las tipo 1, no existiendo significación estadística en la vasculopatía polipoidea. CONCLUSIONES: La NVC tipo1 fue la más observada, y además se relacionó con un mejor pronóstico visual, en comparación con el resto de lesiones neovasculares, en pacientes tratados con ranibizumab

OBJECTIVE: To analyse the incidence and outcomes of the different neovascular subtypes in age-related macular degeneration (AMD). MATERIAL AND METHODS: A retrospective review was carried out on patients with neovascular AMD treated in the University and Polytechnic Hospital la Fe in Valencia by the same retinal physician (RGP) between December 2012 and July 2015. The anatomic classification of the neovascular lesions was recorded, as well as the number of intravitreal treatments administered and the change in visual acuity (VA) obtained throughout the follow-up. RESULTS: A total number of 174 eyes of 156 patients (mean age: 79.9 years) with a minimum follow-up of 4 months were included. The anatomic classification of choroidal neovascularisation (CNV) showed the presence of type 1 lesions in 40,8%, type 2 lesions in 12%, type 3 lesions in 31%, and mixed lesions in 14.4%, with 1.7% showing polypoidal choroidal vasculopathy features. Overall, the mean baseline VA was 0,32, improving to 0,38 at 24 months, after having received a mean of 9.3 injections. Type 2, 3, and mixed forms showed a visual result significantly lower than type1, but there was no significant difference in the polypoidal vasculopathy. CONCLUSIONS: Type 1 CNV was the most common finding, and was associated with a better visual prognosis, compared to the other neovascular lesions

Incidence and clinical outcomes of the different neovascular forms of age-related macular degeneration in Valencia (Spain). / Incidencia y resultados clínicos de las distintas formas neovasculares de degeneración macular asociada a la edad en Valencia (España).

OBJECTIVE: To analyse the incidence and outcomes of the different neovascular subtypes in age-related macular degeneration (AMD). MATERIAL AND METHODS: A retrospective review was carried out on patients with neovascular AMD treated in the University and Polytechnic Hospital la Fe in Valencia by the same retinal physician (RGP) between December 2012 and July 2015. The anatomic classification of the neovascular lesions was recorded, as well as the number of intravitreal treatments administered and the change in visual acuity (VA) obtained throughout the follow-up. RESULTS: A total number of 174 eyes of 156 patients (mean age: 79.9years) with a minimum follow-up of 4 months were included. The anatomic classification of choroidal neovascularisation (CNV) showed the presence of type1 lesions in 40,8%, type2 lesions in 12%, type3 lesions in 31%, and mixed lesions in 14.4%, with 1.7% showing polypoidal choroidal vasculopathy features. Overall, the mean baseline VA was 0,32, improving to 0,38 at 24months, after having received a mean of 9.3 injections. Type2, 3, and mixed forms showed a visual result significantly lower than type1, but there was no significant difference in the polypoidal vasculopathy. CONCLUSIONS: Type 1 CNV was the most common finding, and was associated with a better visual prognosis, compared to the other neovascular lesions.

Birth-weight differences at term are explained by placental dysfunction and not by maternal ethnicity.

OBJECTIVE: To investigate the influence of ethnicity, fetal gender and placental dysfunction on birth weight (BW) in term fetuses of South Asian and Caucasian origin. METHODS: This was a retrospective study of 627 term pregnancies assessed at two public tertiary hospitals in Spain and Sri Lanka. All fetuses underwent biometry and Doppler examinations within 2 weeks of delivery. The influences of fetal gender and ethnicity, gestational age (GA) at delivery, cerebroplacental ratio (CPR) and maternal age, height, weight and parity on BW were evaluated by multivariable regression analysis. RESULTS: Fetuses born in Sri Lanka were smaller than those born in Spain (mean BW = 3026 ± 449 g vs 3295 ± 444 g; P < 0.001). Multivariable regression analysis demonstrated that GA at delivery, maternal weight, CPR, maternal height and fetal gender (estimates = 0.168, P < 0.001; 0.006, P < 0.001; 0.092, P = 0.003; 0.009, P = 0.002; 0.081, P = 0.01, respectively) were associated significantly with BW. Conversely, no significant association was noted for maternal ethnicity, age or parity (estimates = -0.010, P = 0.831; 0.005, P = 0.127; 0.035, P = 0.086, respectively). The findings were unchanged when the analysis was repeated using INTERGROWTH-21st fetal weight centiles instead of BW (log odds, -0.175, P = 0.170 and 0.321, P < 0.001, respectively for ethnicity and CPR). CONCLUSION: Fetal BW variation at term is less dependent on ethnic origin and better explained by placental dysfunction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Persistencia en el tratamiento según el tipo de dispositivo inhalador en pacientes con asma y enfermedad pulmonar obstructiva crónica / Persistence to treatment by type of inhaler device in patients with asthma and chronic obstructive pulmonary disease

Objetivo. Evaluar la persistencia inicial al tratamiento con corticosteroides y beta-2 agonistas de larga duración (CSI/LABA) según el tipo de dispositivo inhalador (MDI o DPI) para el tratamiento del asma y la EPOC. Material y métodos. Estudio observacional multicéntrico. Se incluyeron sujetos en tratamiento inicial con CSI/LABA durante 2007-2011, y con un periodo de seguimiento de 3 años. Se confeccionaron 2 grupos de estudio (asma, EPOC) y 2 subgrupos según el tipo de dispositivo inhalador (MDI o DPI). Las principales medidas fueron: sociodemográficas, comorbilidad, adherencia (ratio de posesión del medicamento, RPM), medicación, exacerbaciones y uso de los recursos y sus costes (directos, indirectos). Se utilizaron modelos multivariantes para la corrección de las variables. Significación estadística: p < 0,05. Resultados. Se seleccionó a 2.082 sujetos asmáticos (MDI: N = 566, 27,2%; DPI: N = 1.516, 72,8%). Los pacientes con dispositivos MDI mostraron un mayor grado de persistencia (32,5 vs. 27,8%; p = 0,037), adherencia al tratamiento (RPM: 83,1 vs. 80,5%; p < 0,001), menos exacerbaciones (17,7 vs. 24,9%; p = 0,001) y menor coste sanitario (2.583 vs. 2.938 EUR; p = 0,042). También se analizaron 1.418 pacientes con EPOC (MDI: N = 594, 41,9%; DPI: N = 824, 58,1%). Los pacientes con dispositivos MDI también mostraron un mayor grado de persistencia (31,5 vs. 24,8%; p = 0,005), adherencia al tratamiento (RPM: 83,3 vs. 80,1%; p = 0,001), menos exacerbaciones (40,1 vs. 48,2%; p = 0,002) y menor coste sanitario (3.922 vs. 4.588 EUR; p = 0,021). Conclusiones. Los dispositivos MDI (tratamiento inicial con CSI/LABA) pueden asociarse a un mayor grado de persistencia en el tratamiento, tanto en asma como en EPOC, con menores tasas de exacerbaciones y consumo de recursos sanitarios y costes (AU)

Objective. To assess the initial treatment persistence with inhaled corticosteroids and long-acting beta-2 adrenergic bronchodilators (ICS/LABA) depending on the inhaler device used (pMDI or DPI), for the treatment of asthma and COPD. Material and methods. An multicenter observational study. Subjects in initial treatment with ICS/LABA during 2007-2011 were included, and a follow-up period of 3 years. 2 groups of study (asthma, COPD) and 2 subgroups were prepared according to the device type inhaler (pMDI or DPI). The main measurements were: sociodemographic, comorbidity, adherence (rate possession medication -RPM-), persistence, drugs, exacerbation rates, resources use, and their costs (direct and indirect costs). Multivariate methods were used for the variables correction, with significance level of P<.05. Results. The study included 2,082 asthma patients (pMDI: N = 566, 27.2%; DPI = 1,516, 72.8%). Patients with MDI devices showed a higher degree of persistence (32.5 vs. 27.8%; P=.037), treatment adherence (RPM: 83.1 vs. 80.5%; P<.001), fewer exacerbations (17.7 vs. 24.9%; P=.001) and lower health care costs (2,583 vs. 2,938 EUR; P = 0.042). 1,418 patients with COPD also were analyzed (pMDI: N = 524, 41.9%; DPI: N = 824, 58.1%) were analyzed. Patients with MDI devices also showed a higher degree of persistence (31.5 vs. 24.8%; P=.005), treatment adherence (RPM: 83.3 vs. 80.1%; P= .001), less exacerbations (40.1 vs. 48.2%; P=.002) and lower health care costs (3,922 vs. 4,588 EUR; P=.021). Conclusions. pMDI devices (as ICS/LABA initial treatment) are associated with higher treatment persistence either in asthma or COPD, with lower exacerbation rates, and use of health resources and cost (AU)

[Persistence to treatment by type of inhaler device in patients with asthma and chronic obstructive pulmonary disease]. / Persistencia en el tratamiento según el tipo de dispositivo inhalador en pacientes con asma y enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To assess the initial treatment persistence with inhaled corticosteroids and long-acting beta-2 adrenergic bronchodilators (ICS/LABA) depending on the inhaler device used (pMDI or DPI), for the treatment of asthma and COPD. MATERIAL AND METHODS: An multicenter observational study. Subjects in initial treatment with ICS/LABA during 2007-2011 were included, and a follow-up period of 3 years. 2 groups of study (asthma, COPD) and 2 subgroups were prepared according to the device type inhaler (pMDI or DPI). The main measurements were: sociodemographic, comorbidity, adherence (rate possession medication -RPM-), persistence, drugs, exacerbation rates, resources use, and their costs (direct and indirect costs). Multivariate methods were used for the variables correction, with significance level of P<.05. RESULTS: The study included 2,082 asthma patients (pMDI: N = 566, 27.2%; DPI = 1,516, 72.8%). Patients with MDI devices showed a higher degree of persistence (32.5 vs. 27.8%; P=.037), treatment adherence (RPM: 83.1 vs. 80.5%; P<.001), fewer exacerbations (17.7 vs. 24.9%; P=.001) and lower health care costs (2,583 vs. 2,938 EUR; P = 0.042). 1,418 patients with COPD also were analyzed (pMDI: N = 524, 41.9%; DPI: N = 824, 58.1%) were analyzed. Patients with MDI devices also showed a higher degree of persistence (31.5 vs. 24.8%; P=.005), treatment adherence (RPM: 83.3 vs. 80.1%; P= .001), less exacerbations (40.1 vs. 48.2%; P=.002) and lower health care costs (3,922 vs. 4,588 EUR; P=.021). CONCLUSIONS: pMDI devices (as ICS/LABA initial treatment) are associated with higher treatment persistence either in asthma or COPD, with lower exacerbation rates, and use of health resources and cost.

Sex addiction and gambling disorder: similarities and differences.

OBJECTIVE: Recently, the DSM-5 has developed a new diagnostic category named "Substance-related and Addictive Disorders". This category includes gambling disorder (GD) as the sole behavioral addiction, but does not include sex addiction (SA). The aim of this study is to investigate whether SA should be classified more closely to other behavioral addictions, via a comparison of the personality characteristics and comorbid psychopathology of individuals with SA with those of individuals with GD, which comes under the category of addiction and related disorders. METHOD: The sample included 59 patients diagnosed with SA, who were compared to 2190 individuals diagnosed with GD and to 93 healthy controls. Assessment measures included the Diagnostic Questionnaire for Pathological Gambling, the South Oaks Gambling Screen, the Symptom CheckList-90 Items-Revised and the Temperament and Character Inventory-Revised. RESULTS: No statistically significant differences were found between the two clinical groups, except for socio-economic status. Although statistically significant differences were found between both clinical groups and controls for all scales on the SCL-90, no differences were found between the two clinical groups. The results were different for personality characteristics: logistic regression models showed that sex addictive behavior was predicted by a higher education level and by lower scores for TCI-R novelty-seeking, harm avoidance, persistence and self-transcendence. Being employed and lower scores in cooperativeness also tended to predict the presence of sex addiction. CONCLUSIONS: While SA and GD share some psychopathological and personality traits that are not present in healthy controls, there are also some diagnostic-specific characteristics that differentiate between the two clinical groups. These findings may help to increase our knowledge of phenotypes existing in behavioral addictions.

[Cellular prion protein in the central nervous system of mammals. Anatomoclinical associations]. / La proteína priónica celular en el sistema nervioso central de mamíferos. Correlatos anatomoclínicos.

INTRODUCTION: The scrapie prion protein (PrPsc) requires the cellular prion protein (PrPc) for its propagation and replication. In this work we studied the expression and localization of the PrPc in the central nervous system (SNC) of the rat, mouse, cat, cow and human, using immunohistochemistry and Western blot techniques to understand more about prionopathies and Alzheimer's disease (EA). MATERIAL AND METHODS: For the immunohistochemistry study we used human, cat, rat and cow samples to analyse frontal, temporal and occipital cortex, as well as the hippocampus and the thalamus. For the Western blot analysis we used mouse, cat, cow and human brain samples. RESULTS: We observed a decrease in the amount of PrPc in the SNC in a rostrocaudal shift in the species mentioned above. We observed inhibitory cells in the cat cortex. The Western blot analysis showed a similar pattern of expression in the different species studied with a preponderance of the diglycosylated band, in relation to the other bands observed in the analysis. DISCUSSION: These data suggest that in prionopathies PrPsc could be transmitted and could be replicated in and from the areas with most expression of PrPc. Similarly, a higher amount of this protein (PrPc) in some brain areas could explain some histopathological aspects of EA. CONCLUSIONS: Our findings support the hypothesis of a retrograde transport of PrPsc in the SNC. PrPc could be related to the pathophysiology of EA.

The cellular prion protein and its role in Alzheimer disease.

The cellular prion protein (PrP(C)) is a membrane-bound glycoprotein especially abundant in the central nervous system (CNS). The scrapie prion protein (PrP(Sc,) also termed prions) is responsible of transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases which affect humans and other mammal species, although the presence of PrP(C) is needed for the establishment and further evolution of prions. The present work compares the expression and localization of PrP(C) between healthy human brains and those suffering from Alzheimer disease (AD). In both situations we have observed a rostrocaudal decrease in the amount of PrP(C) within the CNS, both by immunoblotting and immunohistochemistry techniques. PrP(C) is higher expressed in our control brains than in AD cases. There was a neuronal loss and astogliosis in our AD cases. There was a tendency of a lesser expression of PrP(C) in AD cases than in healthy ones. And in AD cases, the intensity of the expression of the unglycosylated band is higher than the di- and monoglycosylated bands. With regards to amyloid plaques, those present in AD cases were positively labeled for PrP(C), a result which is further supported by the presence of PrP(C) in the amyloid plaques of a transgenic line of mice mimicking AD. The work was done according to Helsinki Declaration of 1975, and approved by the Ethics Committee of the Faculty of Medicine of the University of Navarre.