Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse

Purpose. The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. Methods. Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. Results. The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. Conclusions. Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.

¿Espondiloartropatías atípicas? ¿o simplemente las típicas de las mujeres?

Antecedentes/Objetivos: El desconocimiento de la diferente semiología de las espondiloartropatías (EA) en las mujeres, respecto a su variante en hombres, está en el origen de una menor sospecha diagnóstica y errores diagnósticos en las mujeres; influyendo en la infra-estimación de su prevalencia y desigualdad de género en el acceso al tratamiento. Objetivo: reforzar las diferencias por sexo en los signos/síntomas (S/S) de la EA, la diversidad de errores diagnósticos previos, y el retraso diagnóstico. Métodos: Diseño observacional y análisis de comparación de 2 grupos de pacientes: 96 hombres (H) y 54 mujeres (M) con EA, atendidos durante 1 año (2013-2014) en las consultas de Reumatología del Hospital General Universitario de Alicante. Fuente de información: Cuestionario semi-estructurado e historia clínica (HC) sobre: S/S previos al diagnóstico, retraso diagnóstico e itinerarios sanitarios, y diagnósticos previos alternativos/erróneos. Resultados: Las EA se han confundido con 56 opciones diagnósticas alternativas/erróneas (en un 70,8% de los H y 93,8% de las M). Con los últimos criterios diagnósticos, hay más M: 31,5% que H diagnosticados de EA: 16,7%. El debut de la EA es con 25 síntomas diferentes referidos por los H (11 según HC clínica) y 20 por M (9 en HC), 18 comunes según los referidos por pacientes (7 comunes por HC). Más frecuentes en H: dolor lumbar 25%, de espalda 20,8% y cadera 8,3% vs en M: dolor espalda 22,2%, lumbar 18,5% y pies 14,8%. Los H tardan una media de 14 meses y las M 10, en demandar asistencia sanitaria tras la aparición de los síntomas. Mientras, la media del retraso en la atención médica hasta el diagnóstico de EA es de 7 y 9,75 años en hombres y mujeres, respectivamente; siendo más los especialistas que refieren a los H a Reumatología (n = 14) junto con la atención 1ª, que en las M (n = 8), las cuales son atendidas a petición de ellas (5,6%) y por urgencias 16,7% con > frecuencia que los H (a petición de ellos 1% y por urgencias 6,3%). Conclusiones: No todos los signos y síntomas de las Espondiloatropatías son referidos con la misma frecuencia en uno y otro sexo. Aplicando los nuevos criterios diagnósticos de 2009 se reducen las diferencias por sexo en el diagnóstico de EA. Pero, pese al conocimiento existente, la mímesis de prácticas profesionales diagnósticas obsoletas, como la aplicación de criterios diagnósticos sobrepasados induce a la no sospecha diagnóstica, confusión con diagnósticos erróneos y al retraso en la asistencia sanitaria. Son sesgos de género en el esfuerzo diagnóstico con consecuencias en los itinerarios complejos de los/las pacientes previos al diagnóstico de EA, en el esfuerzo terapéutico y en la prevalencia de las EA, especialmente en mujeres.

Barriers and facilitators to effective coverage of Intimate Partner Violence services for immigrant women in Spain

Objective: To explore service providers’ perceptions in order to identify barriers and facilitators to effective coverage of Intimate Partner Violence (IPV) services for immigrant women in Spain, according to the different categories proposed in Tanahashi's model of effective coverage. Methods: A qualitative study based on 29 in-depth personal interviews and four group interviews with a total of 43 professionals working in public services (social and health-care services, women's refuges, the police force, the judiciary) and NGOs in Barcelona, Madrid, Valencia and Alicante (Spain) in 2011. Findings: Current IPV services in Spain partially fail in their coverage of abused immigrant women due to barriers of (i) availability, such as the inexistence of culturally appropriate services; (ii) accessibility, as having a residence permit is a prerequisite for women's access to different services and rights; (iii) acceptability, such as women's lack of confidence in the effectiveness of services; and (iv) effectiveness, for example, lack of specific training among professionals on the issues of IPV and immigration. However, interviewees also identified facilitators, such as the enabling environment promoted by the Spanish Law on Gender-Based Violence (1/2004), and the impetus it has provided for the development of other specific legislative tools to address IPV in immigrant populations in Spain (availability, accessibility and effectiveness). Conclusion: Whilst not dismissing cultural barriers, aspects related to service structure are identified by providers as the main barriers and facilitators to immigrant women use of IPV services. Despite noteworthy achievements, improvements are still required in terms of mainstreaming assistance tailored to immigrant women's needs in IPV policies and services.

Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects

Background: Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound. Methods: For this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified. Results: Microglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space. Conclusions: These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.

Catheter-related bloodstream infection: burden of disease in a tertiary hospital

Background: Surveillance programmes have become the most effective tool for controlling catheter-related bloodstream infections (CRBSI). However, few studies have investigated programmes covering all hospital settings. Aim: To describe the results of a control and prevention programme for CRBSI based on compliance with recommendations for insertion and maintenance, using annual burden of disease in a tertiary level hospital. Methods: A CRBSI control and prevention programme involving all hospital settings was implemented. The programme consisted of CRBSI surveillance, direct observation of insertion and maintenance of catheters to determine performance, and education for healthcare workers. Findings: In total, 2043 short-term catheters were inserted in 1546 patients for 18,570 catheter-days, and 279 long-term catheters were inserted in 243 patients for 40,440 catheter-days. The annual incidence density was 5.98 (first semester 6.40, second semester 5.64) CRBSI per 1000 catheter-days for short-term catheters, and 0.57 (first semester 0.66, second semester 0.43) CRBSI per 1000 catheter-days for long-term catheters. One hundred and forty insertion procedures were observed, with an average insertion time of 13 (standard deviation 7) min. Compliance with recommendations was as follows: hand hygiene, 86.8%; use of alcoholic chlorhexidine solution for skin disinfection, 35.5%; use of mask, 93.4%; use of gloves, 98.7%; use of gown, 75.0%; use of sterile cloth, 93.8%; use of cap, 92.2%; bandage application, 62.7%; and use of aseptic technique, 89.5%. Forty-five maintenance procedures were observed, and compliance rates were as follows: hand hygiene, 42.1%; use of gloves, 78.1%; and port disinfection with alcoholic chlorhexidine solution, 32.5%. Conclusion: The CRBSI control and prevention programme implemented at the study hospital has decreased the rate of CRBSI, provided important information about the total burden of disease, and revealed possible ways to improve interventions in the future.

Factors Associated with the Cessation of Intimate Partner Violence in Women Attending Primary Care in Spain

This study aimed to identify factors associated with the likelihood of IPV cessation among women attending Spanish primary healthcare. Of the 2465 women who reported lifetime IPV, 36.1 % stated that violence had ceased. Those women not currently abused had higher levels of education and social support, were workers or students, and had no dependent children. When IPV duration was less than 5 years, the likelihood of cessation was two times higher than when IPV continued beyond 5 years. For women who have experienced physical IPV, the probability of ending the violent relationship was 10 times higher than for those suffering from psychological IPV. The implications of the findings regarding clinical significance and future research are discussed.

Validación de la versión española del cuestionario Physician Readiness To Manage Intimate Partner Violence Survey (PREMIS)

Fundamentos: El Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS) es uno de los cuestionarios más completos en el contexto internacional para la valoración de la capacidad de respuesta frente a la violencia del compañero íntimo por los profesionales de Atención Primaria de Salud. El objetivo de este estudio fue determinar la fiabilidad, consistencia interna y validez de constructo de la versión española de este cuestionario. Métodos: Tras la traducción, retrotraducción y valoración de la validez de contenido del cuestionario, se distribuyeron en una muestra de 200 profesionales de medicina y enfermería de 15 centros de atención primaria de 4 Comunidades Autónomas en 2013 (Comunidad Valenciana, Castilla León, Murcia y Cantabria). Se calcularon los coeficientes alfa de Cronbach, los de correlación intraclase y rho de Spearman (test-retest). Resultados: la versión española del PREMIS incluyó 64 ítems. El coeficiente α de Cronbach fue superior a 0,7 o muy cercano a ese valor en la mayoría de los índices. Se obtuvo un coeficiente de correlación intraclase de 0,87 y un coeficiente de Spearman de 0,67 que muestran una fiabilidad alta. Todas las correlaciones observadas para la escala de opiniones, la única tratada como estructura factorial en el cuestionario PREMIS, fueron superiores a 0,30. Conclusiones: el PREMIS en español obtuvo una buena validez interna, alta fiabilidad y capacidad predictiva de las prácticas auto-referidas por médicos(as) y enfermeros(as) frente a casos de violencia del compañero íntimo en centros de atención primaria.

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

Retinal neurodegenerative diseases like age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa each have a different etiology and pathogenesis. However, at the cellular and molecular level, the response to retinal injury is similar in all of them, and results in morphological and functional impairment of retinal cells. This retinal degeneration may be triggered by gene defects, increased intraocular pressure, high levels of blood glucose, other types of stress or aging, but they all frequently induce a set of cell signals that lead to well-established and similar morphological and functional changes, including controlled cell death and retinal remodeling. Interestingly, an inflammatory response, oxidative stress and activation of apoptotic pathways are common features in all these diseases. Furthermore, it is important to note the relevant role of glial cells, including astrocytes, Müller cells and microglia, because their response to injury is decisive for maintaining the health of the retina or its degeneration. Several therapeutic approaches have been developed to preserve retinal function or restore eyesight in pathological conditions. In this context, neuroprotective compounds, gene therapy, cell transplantation or artificial devices should be applied at the appropriate stage of retinal degeneration to obtain successful results. This review provides an overview of the common and distinctive features of retinal neurodegenerative diseases, including the molecular, anatomical and functional changes caused by the cellular response to damage, in order to establish appropriate treatments for these pathologies.

Violence against young women attending primary care services in Spain: prevalence and health consequences

Background. There are a significant number of studies assessing the negative health consequences of violence against women. However, a limited number of studies analyse the health consequences of violence committed against young women by different types of aggressors. Objectives. The goal of this study is to assess the prevalence of interpersonal violence against young women in Spain and analyse its impact on the physical and mental health of the victims. Methods. A total of 1076 women aged 18–25 years attending Spanish primary care services were selected. We estimated the prevalence of interpersonal violence and compared the health data and demographic characteristics of abused and non-abused young women, multi-logistic regression models were fitted. The Wald test was used to assess whether there were differences in the negative health consequences of intimate partner (IPV) versus non-IPV. Results. As many as 27.6% young women reported a history of abuse, of whom 42.7% had been assaulted by their partner, 41.1% by someone other than their partner and 16.2% both by their partner and another person. The distribution of social and demographic characteristics was similar for IPV and non-IPV victims. Young abused women were three times more likely to suffer psychological distress and have somatic complaints, and they were four times more likely to use medication as compared to non-abused women. Conclusion. Our results suggest that all forms of violence compromise young women’s health seriously. Including patients’ history of abuse in their health record may help make more informed clinical decisions and provide a more integrated care.

Racism, Other Discriminations and Effects on Health

We study the probability of perceived racism/other forms of discrimination on immigrant and Spanish populations within different public spheres and show their effect on the health of immigrants using a cross-sectional design (ENS-06). Variables: perceived racism/other forms of discrimination (exposure), socio-demographic (explicative), health indicators (dependent). Frequencies, prevalences, and bivariate/multivariate analysis were conducted separately for men (M) and women (W). We estimated the health problems attributable to racism through the population attributable proportion (PAP). Immigrants perceived more racism than Spaniards in workplace (ORM = 48.1; 95 % CI 28.2–82.2), and receiving health care (ORW = 48.3; 95 % CI 24.7–94.4). Racism and other forms of discrimination were associated with poor mental health (ORM = 5.6; 95 % CI 3.9–8.2; ORW = 7.3; 95 % CI 4.1–13.0) and injury (ORW = 30.6; 95 % CI 13.6–68.7). It is attributed to perceived racism the 80.1 % of consumption of psychotropics (M), and to racism with other forms of discrimination the 52.3 % of cases of injury (W). Racism plays a role as a health determinant.

Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration

All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases.

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.

Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.

Desigualdades de género en la investigación en salud pública y epidemiología en España (2007-2014)

Objetivo: Analizar las desigualdades de género en investigación en salud pública y epidemiología en España, en el periodo 2007-2014. Método: Estudio descriptivo según sexo de posiciones de liderazgo del Centro de Investigación Biomédica en Red (CIBER), especialmente en el área temática de epidemiología y salud pública (CIBERESP) en 2014; de sociedades científicas de salud pública (SESPAS) y epidemiología (SEE), 2009-2014; y de proyectos de investigación solicitados (13.320) y financiados (4699), e importes de convocatorias de Acción Estratégica en Salud (AES), 2007-2013. Resultados: Existe una clara infrarrepresentación de mujeres líderes y contratadas en investigación de excelencia en salud pública (CIBERESP), con predominio de los hombres en puestos de decisión. Aunque los proyectos de investigación de la Acción Estratégica en Salud (AES) liderados por mujeres han crecido ligeramente entre 2007 y 2013, entre los solicitados no alcanzan el 50%, con excepción de los de la Comisión de Salud Pública. La brecha de género es aún mayor en proyectos financiados. Los proyectos liderados por hombres tienen mayor probabilidad de obtener financiación, alcanzando el 29% en los de salud pública. Persiste una segregación horizontal de género en posiciones de reconocimiento científico en congresos de SESPAS y SEE. Conclusiones: La sobrerrepresentación de líderes masculinos en la investigación en salud pública en España debe entenderse como indicador y consecuencia del androcentrismo en las sociedades científicas y los grupos profesionales. Esta situación sexista pone en riesgo la existencia de productos y servicios innovadores desde la perspectiva de género que den respuestas a necesidades y demandas de toda la sociedad. Se necesitan más mujeres en investigación que tengan incorporada esta perspectiva.

Long time remodeling during retinal degeneration evaluated by optical coherence tomography, immunocytochemistry and fundus autofluorescence

Purpose: To characterize the relationship between fundus autofluorescence (FAF), Optical Coherence Tomography (OCT) and immunohistochemistry (IHC) over the course of chronic retinal degeneration in the P23H rat. Methods: Homozygous albino P23H rats, Sprague–Dawley (SD) rats as controls and pigmented Long Evans (LE) rats were used. A Spectralis HRA OCT system was used for scanning laser ophthalmoscopy (SLO) imaging OCT and angiography. To determine FAF, fluorescence was excited using diode laser at 488 nm. A fast retina map OCT was performed using the optic nerve as a landmark. IHC was performed to correlate with the findings of OCT and FAF changes. Results: During the course of retinal degeneration, the FAF pattern evolved from some spotting at 2 months old to a mosaic of hyperfluorescent dots in rats 6 months and older. Retinal thicknesses progressively diminished over the course of the disease. At later stages of degeneration, OCT documented changes in the retinal layers, however, IHC better identified the cell loss and remodeling changes. Angiography revealed attenuation of the retinal vascular plexus with time. Conclusion: We provide for the first time a detailed long-term analysis of the course of retinal degeneration in P23H rats using a combination of SLO and OCT imaging, angiography, FAF and IHC. Although, the application of noninvasive methods enables longitudinal studies and will decrease the number of animals needed for a study, IHC is still an essential tool to identify retinal changes at the cellular level.