Attentional Modulation of Change Detection ERP Components by Peripheral Retro-Cueing

Change detection is essential for visual perception and performance in our environment. However, observers often miss changes that should be easily noticed. A failure in any of the processes involved in conscious detection (encoding the pre-change display, maintenance of that information within working memory, and comparison of the pre and post change displays) can lead to change blindness. Given that unnoticed visual changes in a scene can be easily detected once attention is drawn to them, it has been suggested that attention plays an important role on visual awareness. In the present study, we used behavioral and electrophysiological (ERPs) measures to study whether the manipulation of retrospective spatial attention affects performance and modulates brain activity related to the awareness of a change. To that end, exogenous peripheral cues were presented during the delay period (retro-cues) between the first and the second array using a one-shot change detection task. Awareness of a change was associated with a posterior negative amplitude shift around 228–292 ms (“Visual Awareness Negativity”), which was independent of retrospective spatial attention, as it was elicited to both validly and invalidly cued change trials. Change detection was also associated with a larger positive deflection around 420–580 ms (“Late Positivity”), but only when the peripheral retro-cues correctly predicted the change. Present results confirm that the early and late ERP components related to change detection can be functionally dissociated through manipulations of exogenous retro-cueing using a change blindness paradigmThis work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) grant PSI2014-53743-PS

Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis

Objective Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment. Method A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined. Results Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531). Conclusion VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy

Melatonin receptors MT1 and MT2 are expressed in spermatozoa from several seasonal and nonseasonal breeder species

P. 1958-1968Melatonin is a ubiquitous and multipurpose molecule, and one of its roles is to regulate reproduction in some seasonal mammals. Our group has previously reported the variation in the melatonin levels in ram seminal plasma along the year and identified MT1 and MT2 receptors in ram spermatozoa. The objective of this study was to elucidate whether the presence of melatonin receptors (MT1 and MT2) in the sperm plasma membrane, and melatonin in the seminal plasma is related to seasonal breeding. For this purpose, the presence of melatonin receptors and the levels of melatonin in seminal plasma have been examined in several species: donkey and stallion as long-day breeders; red deer as a wild, short-day, highly seasonal breeder (epididymal spermatozoa); bull as a conventional nonseasonal breeder; boar as a seasonal breeder under management techniques; and dog as possible a seasonal breeder not regulated by melatonin. We have detected measurable levels of melatonin in the seminal plasma of all ejaculated semen samples (from donkey, stallion, boar, bull, and dog). Also, and for the first time, we have demonstrated the presence of MT1 and MT2 melatonin receptors in the spermatozoa of all these species, regardless their type of reproduction or sperm source (ejaculated or epididymal), using indirect immunofluorescence techniques and Western blotting. Our findings suggest that melatonin and melatonin receptors may be universally distributed in the reproductive system of mammals and that the sperm melatonin receptors cells may not be necessarily related with seasonal reproduction. Furthermore, the presence of MT1 at the cytoplasmic droplet in immature ejaculated stallion spermatozoa found in one sample and epididymal red deer spermatozoa suggests that melatonin may be involved in specific functions during spermatogenesis and sperm maturation, like protecting spermatozoa from oxidative damage, this activity being mediated through these receptors.S

Foveal changes in aquaporin‐4 antibody seropositive neuromyelitis optica spectrum disorder are independent of optic neuritis and not overtly progressive

Background and purpose: Foveal changes were reported in aquaporin-4 antibody (AQP4-Ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) patients; however, it is unclear whether they are independent of optic neuritis (ON), stem from subclinical ON or crossover from ON in fellow eyes. Fovea morphometry and a statistical classification approach were used to investigate if foveal changes in NMOSD are independent of ON and progressive. Methods: This was a retrospective longitudinal study of 27 AQP4-IgG + NMOSD patients (49 eyes; 15 ON eyes and 34 eyes without a history of ON [NON eyes]), follow-up median (first and third quartile) 2.32 (1.33-3.28), and 38 healthy controls (HCs) (76 eyes), follow-up median (first and third quartile) 1.95 (1.83-2.54). The peripapillary retinal nerve fibre layer thickness and the volume of combined ganglion cell and inner plexiform layer as measures of neuroaxonal damage from ON were determined by optical coherence tomography. Nineteen foveal morphometry parameters were extracted from macular optical coherence tomography volume scans. Data were analysed using orthogonal partial least squares discriminant analysis and linear mixed effects models. Results: At baseline, foveal shape was significantly altered in ON eyes and NON eyes compared to HCs. Discriminatory analysis showed 81% accuracy distinguishing ON vs. HCs and 68% accuracy in NON vs. HCs. NON eyes were distinguished from HCs by foveal shape parameters indicating widening. Orthogonal partial least squares discriminant analysis discriminated ON vs. NON with 76% accuracy. In a follow-up of 2.4 (20.85) years, no significant time-dependent foveal changes were found. Conclusion: The parafoveal area is altered in AQP4-Ab seropositive NMOSD patients suggesting independent neuroaxonal damage from subclinical ON. Longer follow-ups are needed to confirm the stability of the parafoveal structure over time

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

A visual pathway structure-function relationship in central nervous system conditions mediated by antibodies (AQP4-IgG AND MOG-IgG)

La neuritis òptica (ON) és una manifestació inicial comuna al trastorn de l'espectre de la neuromielitis òptica (AQP4-NMOSD) i la malaltia associada a anticossos anti-MOG (MOGAD), que són malalties inflamatòries rares del sistema nerviós central mediades per anticossos. A dia d'avui, no és clar si aquests pacients presenten dany subclínic de la via visual i si aquest s'acumula amb el temps, especialment a MOGAD. Per abordar aquestes preguntes, aquesta tesi proposa un estudi de línia base per interrogar dues de les cohorts més grans de AQP4-NMOSD i MOGAD disponibles, juntament amb una població de control sana aparellada, utilitzant tomografia de coherència òptica (OCT), potencials evocats visuals (PEV), morfometria de la fòvea i proves clíniques per avaluar els patrons diferencials de dany retinià en aquestes dues malalties, amb dades longitudinals per a un subconjunt de casos. A AQP4 NMOSD aquesta tesi demostra, a més del dany neuro axonal esperat als ulls amb història d'ON, una afectació dels ulls contralaterals i dels ulls "mai afectats" (de pacients sense antecedents d'ON). Aquest dany es caracteritza per pèrdua total del volum macular i engrossiment significatiu a la capa nuclear interna (INL) respectivament. Per explorar si aquestes observacions podrien atribuir-se a esdeveniments desmielinitzants inflamatoris del nervi òptic o al mal a les cèl·lules de Müller que expressen AQP4 a la fòvea en absència de una ON clínicament evident, es van avaluar en detall els canvis microestructurals a la retina de pacients amb AQP4-NMOSD analitzant la morfometria de la fòvea. Aquesta tesi demostra que l'àrea parafoveal està alterada en pacients AQP4-NMOSD que mai van experimentar esdeveniments clínics inflamatoris desmielinitzants de la via visual anterior; sent probable que aquests canvas siguin independents del dany neuro axonal relacionat amb esdeveniments desmielinitzants inflamatoris del nervi òptic, ja que les capes macular i peripapillar semblen no estar afectades als ulls sense història d'ON. Els temps de recuperació post-ON es van estudiar tant a AQ4 NMOSD com a MOGAD; Els ulls afectats (bilateralment o unilateralment) i els seus contralaterals sans en AQP4-NMOSD van mostrar una recuperació perllongada després de la fase aguda al volum macular total (mitjana de 0,08 mm3 i 0,35 mm3 per any, respectivament) mentre que es va trobar una disminució significativa en el gruix foveal (mitjana -0,06 μm per any) en ulls de 21 pacients sense prèvia història d'ON. A MOGAD, els volums maculars i el gruix foveal es van conservar en línia base i longitudinalment a tots els ulls no afectats per ON i no van mostrar diferències amb aquells de subjectes sans. Finalment, aquesta tesi investiga els canvis subclínics de la via visual en pacients amb AQP4-NMOSD i MOGAD amb funció visual central normal i la seva relació amb els resultats d'agudesa visual, demostrant que les anomalies visuals subclíniques (PEV retardat i pèrdua de gruix de les capes internes de la retina) poden ocórrer sense símptomes, i encara que es desconeix la rellevància d'aquestes anomalies subclíniques, el dany acumulatiu bé podria conduir al deteriorament clínic. A més, aquesta tesi demostra una sensibilitat més gran de l'OCT sobre els PEV en la detecció d'aquest dany subclínic en pacients MOGAD amb funció visual normal. En conclusió, he mostrat en aquesta tesi diferents patrons d'afectació de la via visual a AQP4-NMOSD i MOGAD i ressaltat la importància de l'ús de l'OCT i la morfometria de la fòvea per determinar el dany retinià asimptomàtic. Aquestes dades poden no només millorar el diagnòstic diferencial i el maneig dels pacients, sinó també contribuir a la comprensió dels mecanismes subjacents de la malaltia i la patogènia d'aquests dos trastorns.La neuritis óptica (ON) es una manifestación inicial común en el trastorno del espectro de la neuromielitis óptica (AQP4-NMOSD) y la enfermedad asociada a anticuerpos anti-MOG (MOGAD), que son enfermedades inflamatorias raras del sistema nervioso central mediadas por anticuerpos. A día de hoy, no está claro si estos pacientes presentan daño subclínico de la vía visual y si este se acumula con el tiempo, especialmente en MOGAD. Para abordar estas preguntas, esta tesis propone un estudio de línea base para interrogar a dos de las cohortes más grandes de AQP4-NMOSD y MOGAD disponibles, junto con una población de control sana emparejada, utilizando tomografía de coherencia óptica (OCT), potenciales evocados visuales (PEV), morfometría de la fóvea y pruebas clínicas para evaluar los patrones diferenciales de daño retiniano en estas dos enfermedades, con datos longitudinales para un subconjunto de casos. En AQP4-NMOSD esta tesis demuestra, además del daño neuro axonal esperado en ojos con historia de ON, una afectación de los ojos contralaterales y de los ojos "nunca afectados" (de pacientes sin antecedentes de ON). Dicho daño se caracteriza por pérdida total del volumen macular y engrosamiento significativo en la capa nuclear interna (INL) respectivamente. Para explorar si estas observaciones podrían atribuirse a eventos desmielinizantes inflamatorios del nervio óptico o al daño a las células de Müller que expresan AQP4 en la fóvea en ausencia de una ON clínicamente evidente, se evaluaron en detalle los cambios microestructurales en la retina de pacientes con AQP4-NMOSD analizando la morfometría de la fóvea. Esta tesis demuestra que el área parafoveal está alterada en pacientes AQP4-NMOSD que nunca experimentaron eventos clínicos inflamatorios desmielinizantes de la vía visual anterior; siendo probable que estos cambios sean independientes del daño neuro axonal relacionado con eventos desmielinizantes inflamatorios del nervio óptico, ya que las capas macular y peripapilar parecen no estar afectadas en ojos sin historia de ON. Los tiempos de recuperación post- ON se estudiaron tanto en AQ4-NMOSD como en MOGAD; Los ojos afectados (bilateral o unilateralmente) y sus contralaterales sanos en AQP4- NMOSD mostraron una recuperación prolongada después de la fase aguda en el volumen macular total (media de 0,08 mm3 y 0,35 mm3 por año, respectivamente) mientras que se encontró una disminución significativa en el grosor foveal (media -0,06 μm por año) en ojos de 21 pacientes sin previa historia de ON. En MOGAD, los volúmenes maculares y el grosor foveal se conservaron en línea base y longitudinalmente en todos los ojos no afectados por ON y no mostraron diferencias con aquellos de sujetos sanos. Finalmente, esta tesis investiga los cambios subclínicos de la vía visual en pacientes con AQP4-NMOSD y MOGAD con función visual central normal y su relación con los resultados de agudeza visual, demostrando que las anomalías visuales subclínicas (PEV retardado y perdida de grosor de las capas internas de la retina) pueden ocurrir sin síntomas, y aunque se desconoce la relevancia de estas anomalías subclínicas, el daño acumulativo bien podría conducir al deterioro clínico. Además, esta tesis demuestra una mayor sensibilidad del OCT sobre los PEV en la detección de dicho daño subclínico en pacientes MOGAD con función visual normal. En conclusión, en esta tesis he mostrado diferentes patrones de afectación de la vía visual en AQP4-NMOSD y MOGAD y resaltado la importancia del uso de la OCT y la morfometría de la fóvea para determinar el daño retiniano asintomático. Estos datos pueden no solo mejorar el diagnóstico diferencial y el manejo de los pacientes, sino también contribuir a la comprensión de los mecanismos subyacentes de la enfermedad y la patogenia de estos dos trastornos.Optic Neuritis (ON) is a common initial manifestation in Aquaporin-4 - Neuromyelitis Optica spectrum disease (AQP4-NMOSD) and Myelin oligodendrocyte glycoprotein (MOGAD), which are rare inflammatory antibody-mediated disorders of the central nervous system. Whether there is subclinical visual pathway damage and whether this accumulates overtime is unclear, especially in MOGAD. To address these questions, I have set up a cross-sectional study to interrogate two of the largest cohorts of AQP4-NMOSD and MOGAD in the world along with a matched healthy control population. Using optic coherence tomography (OCT), visual evoked potentials (VEP), detailed foveal morphometry and clinical outcomes I assessed the differential patterns of retinal damage in these two conditions. Longitudinal data was available in a subset of cases. In AQP4-NMOSD, beyond the ON eye, I demonstrated that the retina was affected in fellow eyes and "never affected" eyes (from patients with no previous history of ON), this was characterised by total macular volume loss and significant thickening in inner nuclear layer (INL) respectively. To explore whether these observations could be attributed to subclinical inflammatory demyelinating events of the optic nerve, or to a foveal damage in AQP4-expressing Müller cells in the absence of clinically overt ON, microstructural changes in the retina of AQP4-NMOSD patients were assessed in detail with foveal morphometry analysis. I have shown that the parafoveal area is altered in AQP4-NMOSD patients who never experienced clinical inflammatory demyelinating events of the anterior visual pathway, while they are minor compared with those with ON events, these changes are likely to be independent from neuroaxonal damage related to subclinical inflammatory demyelinating events of the optic nerve, as macular and peripapillary layers appeared not to be affected in the subset of those without history of ON. Recovery times after ON were studied in both AQ4-NMOSD and MOGAD; affected and fellow AQP4-NMOSD eyes showed a prolonged recovery after the acute phase in total macular volume (mean 0.08mm3 and 0.35mm3 per year respectively) while a significant decrease in foveal thickness (mean - 0.06 μm per year) was found in "never affected" eyes. In MOGAD macular volumes and foveal thickness were preserved 19 cross-sectionally and longitudinally in all eyes not affected by ON. Finally, I investigated subclinical visual pathway changes and pathophysiological mechanisms of retinal damage in AQP4-NMOSD and MOGAD patients with normal central visual function and its relation to visual function outcomes. I demonstrate that subclinical visual abnormalities (delayed VEP and inner retinal layers thinning) can occur without symptoms and although the relevance of the subclinical abnormalities is unknown, cumulative damage could well lead to clinical impairment, moreover, OCT has proved to have greater sensitivity than VEPs in detecting subclinical damage in MOGAD patients with normal visual function. In conclusion, in this thesis I have shown different patterns of visual pathway involvement in AQP4-NMOSD and MOGAD and highlighted the importance of the use of OCT and foveal morphometry to determine subclinical retinal damage. This data may not only improve differential diagnosis and management but also contribute to the understanding of the underlying disease mechanisms and pathogenesis of these two disorders

A visual pathway structure-function relationship in central nervous system conditions mediated by antibodies (AQP4-IgG AND MOG-IgG)

La neuritis òptica (ON) és una manifestació inicial comuna al trastorn de l’espectre de la neuromielitis òptica (AQP4-NMOSD) i la malaltia associada a anticossos anti-MOG (MOGAD), que són malalties inflamatòries rares del sistema nerviós central mediades per anticossos. A dia d’avui, no és clar si aquests pacients presenten dany subclínic de la via visual i si aquest s’acumula amb el temps, especialment a MOGAD. Per abordar aquestes preguntes, aquesta tesi proposa un estudi de línia base per interrogar dues de les cohorts més grans de AQP4-NMOSD i MOGAD disponibles, juntament amb una població de control sana aparellada, utilitzant tomografia de coherència òptica (OCT), potencials evocats visuals (PEV), morfometria de la fòvea i proves clíniques per avaluar els patrons diferencials de dany retinià en aquestes dues malalties, amb dades longitudinals per a un subconjunt de casos. A AQP4 NMOSD aquesta tesi demostra, a més del dany neuro axonal esperat als ulls amb història d’ON, una afectació dels ulls contralaterals i dels ulls “mai afectats” (de pacients sense antecedents d’ON). Aquest dany es caracteritza per pèrdua total del volum macular i engrossiment significatiu a la capa nuclear interna (INL) respectivament. Per explorar si aquestes observacions podrien atribuir-se a esdeveniments desmielinitzants inflamatoris del nervi òptic o al mal a les cèl·lules de Müller que expressen AQP4 a la fòvea en absència de una ON clínicament evident, es van avaluar en detall els canvis microestructurals a la retina de pacients amb AQP4-NMOSD analitzant la morfometria de la fòvea. Aquesta tesi demostra que l’àrea parafoveal està alterada en pacients AQP4-NMOSD que mai van experimentar esdeveniments clínics inflamatoris desmielinitzants de la via visual anterior; sent probable que aquests canvas siguin independents del dany neuro axonal relacionat amb esdeveniments desmielinitzants inflamatoris del nervi òptic, ja que les capes macular i peripapillar semblen no estar afectades als ulls sense història d’ON. Els temps de recuperació post-ON es van estudiar tant a AQ4 NMOSD com a MOGAD; Els ulls afectats (bilateralment o unilateralment) i els seus contralaterals sans en AQP4-NMOSD van mostrar una recuperació perllongada després de la fase aguda al volum macular total (mitjana de 0,08 mm3 i 0,35 mm3 per any, respectivament) mentre que es va trobar una disminució significativa en el gruix foveal (mitjana -0,06 μm per any) en ulls de 21 pacients sense prèvia història d’ON. A MOGAD, els volums maculars i el gruix foveal es van conservar en línia base i longitudinalment a tots els ulls no afectats per ON i no van mostrar diferències amb aquells de subjectes sans. Finalment, aquesta tesi investiga els canvis subclínics de la via visual en pacients amb AQP4-NMOSD i MOGAD amb funció visual central normal i la seva relació amb els resultats d’agudesa visual, demostrant que les anomalies visuals subclíniques (PEV retardat i pèrdua de gruix de les capes internes de la retina) poden ocórrer sense símptomes, i encara que es desconeix la rellevància d’aquestes anomalies subclíniques, el dany acumulatiu bé podria conduir al deteriorament clínic. A més, aquesta tesi demostra una sensibilitat més gran de l’OCT sobre els PEV en la detecció d’aquest dany subclínic en pacients MOGAD amb funció visual normal. En conclusió, he mostrat en aquesta tesi diferents patrons d’afectació de la via visual a AQP4-NMOSD i MOGAD i ressaltat la importància de l’ús de l’OCT i la morfometria de la fòvea per determinar el dany retinià asimptomàtic. Aquestes dades poden no només millorar el diagnòstic diferencial i el maneig dels pacients, sinó també contribuir a la comprensió dels mecanismes subjacents de la malaltia i la patogènia d’aquests dos trastorns.La neuritis óptica (ON) es una manifestación inicial común en el trastorno del espectro de la neuromielitis óptica (AQP4-NMOSD) y la enfermedad asociada a anticuerpos anti-MOG (MOGAD), que son enfermedades inflamatorias raras del sistema nervioso central mediadas por anticuerpos. A día de hoy, no está claro si estos pacientes presentan daño subclínico de la vía visual y si este se acumula con el tiempo, especialmente en MOGAD. Para abordar estas preguntas, esta tesis propone un estudio de línea base para interrogar a dos de las cohortes más grandes de AQP4-NMOSD y MOGAD disponibles, junto con una población de control sana emparejada, utilizando tomografía de coherencia óptica (OCT), potenciales evocados visuales (PEV), morfometría de la fóvea y pruebas clínicas para evaluar los patrones diferenciales de daño retiniano en estas dos enfermedades, con datos longitudinales para un subconjunto de casos. En AQP4-NMOSD esta tesis demuestra, además del daño neuro axonal esperado en ojos con historia de ON, una afectación de los ojos contralaterales y de los ojos “nunca afectados” (de pacientes sin antecedentes de ON). Dicho daño se caracteriza por pérdida total del volumen macular y engrosamiento significativo en la capa nuclear interna (INL) respectivamente. Para explorar si estas observaciones podrían atribuirse a eventos desmielinizantes inflamatorios del nervio óptico o al daño a las células de Müller que expresan AQP4 en la fóvea en ausencia de una ON clínicamente evidente, se evaluaron en detalle los cambios microestructurales en la retina de pacientes con AQP4-NMOSD analizando la morfometría de la fóvea. Esta tesis demuestra que el área parafoveal está alterada en pacientes AQP4-NMOSD que nunca experimentaron eventos clínicos inflamatorios desmielinizantes de la vía visual anterior; siendo probable que estos cambios sean independientes del daño neuro axonal relacionado con eventos desmielinizantes inflamatorios del nervio óptico, ya que las capas macular y peripapilar parecen no estar afectadas en ojos sin historia de ON. Los tiempos de recuperación post- ON se estudiaron tanto en AQ4-NMOSD como en MOGAD; Los ojos afectados (bilateral o unilateralmente) y sus contralaterales sanos en AQP4- NMOSD mostraron una recuperación prolongada después de la fase aguda en el volumen macular total (media de 0,08 mm3 y 0,35 mm3 por año, respectivamente) mientras que se encontró una disminución significativa en el grosor foveal (media -0,06 μm por año) en ojos de 21 pacientes sin previa historia de ON. En MOGAD, los volúmenes maculares y el grosor foveal se conservaron en línea base y longitudinalmente en todos los ojos no afectados por ON y no mostraron diferencias con aquellos de sujetos sanos. Finalmente, esta tesis investiga los cambios subclínicos de la vía visual en pacientes con AQP4-NMOSD y MOGAD con función visual central normal y su relación con los resultados de agudeza visual, demostrando que las anomalías visuales subclínicas (PEV retardado y perdida de grosor de las capas internas de la retina) pueden ocurrir sin síntomas, y aunque se desconoce la relevancia de estas anomalías subclínicas, el daño acumulativo bien podría conducir al deterioro clínico. Además, esta tesis demuestra una mayor sensibilidad del OCT sobre los PEV en la detección de dicho daño subclínico en pacientes MOGAD con función visual normal. En conclusión, en esta tesis he mostrado diferentes patrones de afectación de la vía visual en AQP4-NMOSD y MOGAD y resaltado la importancia del uso de la OCT y la morfometría de la fóvea para determinar el daño retiniano asintomático. Estos datos pueden no solo mejorar el diagnóstico diferencial y el manejo de los pacientes, sino también contribuir a la comprensión de los mecanismos subyacentes de la enfermedad y la patogenia de estos dos trastornos.Optic Neuritis (ON) is a common initial manifestation in Aquaporin-4 - Neuromyelitis Optica spectrum disease (AQP4-NMOSD) and Myelin oligodendrocyte glycoprotein (MOGAD), which are rare inflammatory antibody-mediated disorders of the central nervous system. Whether there is subclinical visual pathway damage and whether this accumulates overtime is unclear, especially in MOGAD. To address these questions, I have set up a cross-sectional study to interrogate two of the largest cohorts of AQP4-NMOSD and MOGAD in the world along with a matched healthy control population. Using optic coherence tomography (OCT), visual evoked potentials (VEP), detailed foveal morphometry and clinical outcomes I assessed the differential patterns of retinal damage in these two conditions. Longitudinal data was available in a subset of cases. In AQP4-NMOSD, beyond the ON eye, I demonstrated that the retina was affected in fellow eyes and “never affected” eyes (from patients with no previous history of ON), this was characterised by total macular volume loss and significant thickening in inner nuclear layer (INL) respectively. To explore whether these observations could be attributed to subclinical inflammatory demyelinating events of the optic nerve, or to a foveal damage in AQP4-expressing Müller cells in the absence of clinically overt ON, microstructural changes in the retina of AQP4-NMOSD patients were assessed in detail with foveal morphometry analysis. I have shown that the parafoveal area is altered in AQP4-NMOSD patients who never experienced clinical inflammatory demyelinating events of the anterior visual pathway, while they are minor compared with those with ON events, these changes are likely to be independent from neuroaxonal damage related to subclinical inflammatory demyelinating events of the optic nerve, as macular and peripapillary layers appeared not to be affected in the subset of those without history of ON. Recovery times after ON were studied in both AQ4-NMOSD and MOGAD; affected and fellow AQP4-NMOSD eyes showed a prolonged recovery after the acute phase in total macular volume (mean 0.08mm3 and 0.35mm3 per year respectively) while a significant decrease in foveal thickness (mean - 0.06 μm per year) was found in “never affected” eyes. In MOGAD macular volumes and foveal thickness were preserved 19 cross-sectionally and longitudinally in all eyes not affected by ON. Finally, I investigated subclinical visual pathway changes and pathophysiological mechanisms of retinal damage in AQP4-NMOSD and MOGAD patients with normal central visual function and its relation to visual function outcomes. I demonstrate that subclinical visual abnormalities (delayed VEP and inner retinal layers thinning) can occur without symptoms and although the relevance of the subclinical abnormalities is unknown, cumulative damage could well lead to clinical impairment, moreover, OCT has proved to have greater sensitivity than VEPs in detecting subclinical damage in MOGAD patients with normal visual function. In conclusion, in this thesis I have shown different patterns of visual pathway involvement in AQP4-NMOSD and MOGAD and highlighted the importance of the use of OCT and foveal morphometry to determine subclinical retinal damage. This data may not only improve differential diagnosis and management but also contribute to the understanding of the underlying disease mechanisms and pathogenesis of these two disorders.Universitat Autònoma de Barcelona. Programa de Doctorat en Medicin

New records of the invasive alien plant pest Halyomorpha halys (Stål, 1855) in the Iberian Peninsula (Heteroptera: Pentatomidae)

Se cita per primera vegada l'espècie invasora Halyomorpha halys (Stål, 1855) a la província de Barcelona. Les noves localitats són a un centenar de kilòmetres més al sud de la primera troballa de l'espècie a la península Ibèrica. S'alerta de la importància econòmica que comporta aquesta plaga en cultius extensius, de fruiters o d'horta. No cal menysprear les molèsties per a la població quan l'insecte es congrega en els edificis per a hibernar-hi.The brown marmorated stink bug Halyomorpha halys (Stål, 1855) is reported in the province of Barcelona for the first time. Now locations are a hundred kilometer southwards from the first report in the Iberian Peninsula. An alert is made due to the economic importance that this plant pest species has on field, fruit and vegetable crops. Nuisance to people when insects congregate inside buildings to overwinter is not negligible either

NHS Health Check attendance is associated with reduced multiorgan disease risk: a matched cohort study in the UK Biobank

Abstract Background The NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not. Methods Within the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records. These participants were then covariate-matched on an extensive range of socio-demographic, lifestyle, and medical factors with 48,602 participants without record of the check. Follow-up diagnoses were ascertained from health records over an average of 9 years (SD 2 years) including hypertension, diabetes, hypercholesterolaemia, stroke, dementia, myocardial infarction, atrial fibrillation, heart failure, fatty liver disease, alcoholic liver disease, liver cirrhosis, liver failure, acute kidney injury, chronic kidney disease (stage 3 +), cardiovascular mortality, and all-cause mortality. Time-varying survival modelling was used to compare adjusted outcome rates between the groups. Results In the immediate 2 years after the NHS Health Check, higher diagnosis rates were observed for hypertension, high cholesterol, and chronic kidney disease among health check recipients compared to their matched counterparts. However, in the longer term, NHS Health Check recipients had significantly lower risk across all multiorgan disease outcomes and reduced rates of cardiovascular and all-cause mortality. Conclusions The NHS Health Check is linked to reduced incidence of disease across multiple organ systems, which may be attributed to risk modification through earlier detection and treatment of key risk factors such as hypertension and high cholesterol. This work adds important evidence to the growing body of research supporting the effectiveness of preventative interventions in reducing longer-term multimorbidity