Visual Fixation of Skull-Vibration-Induced Nystagmus in Patients with Peripheral Vestibulopathy.

Nystagmus induced by applying an intense vibratory stimulus to the skull (SVIN) indicates vestibular functional asymmetry. In unilateral vestibular loss, a 100 Hz bone-conducted vibration given to either mastoid immediately causes a primarily horizontal nystagmus. The test is performed in darkness to avoid visual fixation (VF) but there are no data about how much VF affects the often-intense SVIN. The aim is to analyze the amount of reduction in SVIN when VF is allowed during testing. Thus, all patients seen in a tertiary hospital for vertigo or dizziness with positive SVIN were included. SVIN was recorded for 10 s for each condition: without VF (aSVINwo) and with VF (aSVINw). We obtained an aSVINwo and an aSVINw as average slow-phase velocities (SPV) without and with VF. VF index (FISVIN) was calculated as the ratio of SPV. Among the 124 patients included, spontaneous nystagmus (SN) was found in 25% and the median slow phase velocity (mSPV) (without VF) of SN was 2.6 ± 2.4°/s. Mean FISVIN was 0.27 ± 0.29. FISVIN was 0 in 42 patients, and FISVIN between 0 and 1 was found in 82 (mean FISVIN 0.39 ± 0.02). Fixation suppression was found in all patients with SVIN in cases of peripheral vestibulopathy. FISVIN clearly delineates two populations of patients: with or without a complete visual reduction in nystagmus.

A retrospective study of deep learning generalization across two centers and multiple models of X-ray devices using COVID-19 chest-X rays.

Generalization of deep learning (DL) algorithms is critical for the secure implementation of computer-aided diagnosis systems in clinical practice. However, broad generalization remains to be a challenge in machine learning. This research aims to identify and study potential factors that can affect the internal validation and generalization of DL networks, namely the institution where the images come from, the image processing applied by the X-ray device, and the type of response function of the X-ray device. For these purposes, a pre-trained convolutional neural network (CNN) (VGG16) was trained three times for classifying COVID-19 and control chest radiographs with the same hyperparameters, but using different combinations of data acquired in two institutions by three different X-ray device manufacturers. Regarding internal validation, the addition of images from an external institution to the training set did not modify the algorithm's internal performance, however, the inclusion of images acquired by a device from a different manufacturer decreased the performance up to 8% (p < 0.05). In contrast, generalization across institutions and X-ray devices with the same type of response function was achieved. Nonetheless, generalization was not observed across devices with different types of response function. This factor was the key impediment to achieving broad generalization in our research, followed by the device's image-processing and the inter-institutional differences, which both reduced generalization performance to 18.9% (p < 0.05), and 9.8% (p < 0.05), respectively. Finally, clustering analysis with features extracted by the CNN was performed, revealing a substantial dependence of feature values extracted by the pre-trained CNN on the X-ray device which acquired the images.

Reverse Phase HPLC Methodology for the Determination of Bay K8644.

Following ICH guidelines for analytical validation, we report a common C18 column stability indicating isocratic reverse phase high performance liquid chromatography method for the determination of the ion channel modulator Bay K8644. Two main forced degradation products and a minor impurity were also tentatively identified by Mass Spectrometry. The mobile phase consisted of a 50/50 acetonitrile/buffer mixture at a flow rate of 2 mL/min. Mean retention time for Bay K8644 was 3.030 minutes. Excellent linearity (r = 0.9998) was achieved in the range 0.10-1.40 µg/mL at 274 nm wavelength. Analytical limits were 16.56 ± 1.04 ng/mL for detection and 55.21 ± 3.48 ng/mL for quantitation respectively. Accuracy and precision studies showed good results (95-105%). Robustness was assessed by varying ±3%, both temperature and flow rate. Five different stress conditions were applied to assess Bay K8644's stability. Only basic and photolytic treatments yielded degradation products, both correctly resolved in a total runtime of 4 minutes. In conclusion, we developed a fast, simple, sensitive, accurate, precise, reliable and stability indicating method for detecting/quantifying Bay K8644, and tentatively characterized its main impurities/forced degradation products.

Special Issue "Aquaporins in Brain Disease".

Water is an abundant and important component of the human brain, the homeostasis of which is rigorously controlled [...].

Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain.

AIMS: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. METHODS: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. RESULTS: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. CONCLUSION: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.

Some aspects of the life of SARS-CoV-2 ORF3a protein in mammalian cells.

The accessory protein ORF3a, from SARS-CoV-2, plays a critical role in viral infection and pathogenesis. Here, we characterized ORF3a assembly, ion channel activity, subcellular localization, and interactome. At the plasma membrane, ORF3a exists mostly as monomers and dimers, which do not alter the native cell membrane conductance, suggesting that ORF3a does not function as a viroporin at the cell surface. As a membrane protein, ORF3a is synthesized at the ER and sorted via a canonical route. ORF3a overexpression induced an approximately 25% increase in cell death. By developing an APEX2-based proximity labeling assay, we uncovered proteins proximal to ORF3a, suggesting that ORF3a recruits some host proteins to weaken the cell. In addition, it exposed a set of mitochondria related proteins that triggered mitochondrial fission. Overall, this work can be an important instrument in understanding the role of ORF3a in the virus pathogenicity and searching for potential therapeutic treatments for COVID-19.

Preterm-related posthemorrhagic hydrocephalus: Review of our institutional series with a long-term follow-up / Hidrocefalia poshemorrágica del prematuro: revisión de nuestra serie a largo plazo

Introduction Preterm-related posthemorrhagic hydrocephalus is a major cause of neurological impairment and a common indication for a ventriculoperitoneal shunt in infants that are prone to diverse complications. Protocols of diagnosis and treatment are in continuous evolution and require evaluation of their results. Objective To review the clinical characteristics and results of a series of preterm-related posthemorrhagic hydrocephalus needing a definitive shunt from 1982 to 2020 in our institution. As a secondary objective we evaluated the safety of the changes in our protocol of treatment from 2015. Methods Retrospective review, clinical investigation. Results 133 patients were implanted a shunt in the study period. Shunt infection was diagnosed in 15 patients. Proximal shunt obstruction as the first complication was diagnosed in 30% of cases at one year, 37% at two years and 46% at five years. 61 patients developed very small or collapsed ventricles at last follow-up. Two thirds of our patients achieved normal neurological development or mild impairment. Changes in protocol did not significantly modify clinical results although improvement in most outcomes was observed. Mean follow-up was over nine years. Conclusions Clinical outcomes are comparable to previous reported data. Changes in protocol proved to be safe and improved our results. Programmable shunts can be used safely in preterm patients although they may not prevent tendency towards ventricular collapse, which is very common after long follow-up (AU)

Antecedentes La hidrocefalia poshemorrágica del prematuro continúa siendo una causa importante de lesión cerebral perinatal y una indicación frecuente de cirugía derivativa valvular en un grupo de pacientes particularmente vulnerable y expuesto a complicaciones. Los protocolos de diagnóstico y tratamiento están en continua evolución y requieren un análisis de los resultados asociados a ellos. Objetivo Revisar las características clínicas y los resultados de tratamiento en una serie de prematuros con hidrocefalia poshemorrágica en los que se implantó una derivación ventriculoperitoneal permanente en nuestro hospital entre 1982 y 2000. Como objetivo secundario evaluamos la seguridad de los cambios introducidos en nuestro protocolo desde 2015. Material y método Estudio clínico retrospectivo, serie de casos. Resultados 133 prematuros requirieron una derivación ventriculoperitoneal permanente en el tiempo de estudio. En 15 de ellos se diagnosticó una infección del sistema de derivación. La obstrucción proximal de la derivación como primera complicación posquirúrgica ocurrió en un 30% de los pacientes al primer año, en el 37% de los pacientes a los dos años y en el 46% de los casos a los 5 años de seguimiento. 61 pacientes desarrollaron un colapso ventricular clínico o radiológico. Dos tercios de los pacientes presentaron un desarrollo psicomotor normal o un retraso de carácter leve. Los cambios incorporados en nuestro protocolo de tratamiento no modificaron la evolución clínica significativamente, aunque se asociaron a una evolución globalmente más favorable. La media de seguimiento fue superior a los 9 años. Conclusiones Los resultados clínicos presentados se encuentran en línea con las series publicadas, Los cambios incorporados en nuestro protocolo actualizado demostraron ser seguros y pueden asociarse a una evolución más favorable (AU)

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPGco / Estudio multicéntrico colaborativo del manejo neuroquirúrgico del craneofaringioma pediátrico en España: S-PedCPGco

Purpose To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. Methods We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. Results The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7–357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. Conclusions Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity (AU)

Objetivo Presentar un análisis descriptivo de los craneofaringiomas pediátricos tratados en varios hospitales españoles, definiendo los factores relacionados con la recurrencia y realizando un análisis crítico de los resultados. Métodos Estudio retrospectivo multicéntrico de los craneofaringiomas pediátricos tratados entre 2000-2017. Se recogieron variables epidemiológicas, clínicas y radiológicas, el objetivo de la primera cirugía, la tasa de recurrencia y su abordaje, los tratamientos adyuvantes, así como las complicaciones y la morbilidad permanente. Se estudió la relación estadística entre la progresión y el número de progresiones con las variables independientes. Resultados Se incluyeron 69 niños tratados en 8 hospitales españoles. La mayoría de los tumores se extendían por varios compartimentos intracraneales al diagnóstico, con invasión hipotalámica en el 41,3%. Habitualmente, la primera estrategia de tratamiento fue la resección radical (71%), con algunos pacientes tratados con radioterapia o quimioterapia intraquística. La tasa de progresión tras la primera cirugía fue del 53% en un seguimiento medio de 88,2 meses (rango 7-357). En el grupo de resección radical recurrieron un 38,8% de los tumores, un 40% en el de resección subtotal o biopsia y un 93,3% en el de fenestración quística±reservorio Ommaya. La mortalidad fue de un 7,2%. Las variables relacionadas de forma significativa con progresión fueron el tiempo de seguimiento, el tamaño del tumor y el objetivo de la primera cirugía. Conclusiones Los resultados obtenidos fueron aceptables en control de la enfermedad, secuelas hormonales o visuales y mortalidad, aunque hay varias áreas susceptibles de mejora. Nuestros objetivos a corto plazo deberían estar orientados a crear un registro nacional de craneofaringiomas pediátricos, alcanzar un consenso respecto al algoritmo de tratamiento y mejorar el diagnóstico de la disfunción hipotalámica para evitar morbilidad (AU)

Preterm-related posthemorrhagic hydrocephalus: Review of our institutional series with a long-term follow-up.

INTRODUCTION: Preterm-related posthemorrhagic hydrocephalus is a major cause of neurological impairment and a common indication for a ventriculoperitoneal shunt in infants that are prone to diverse complications. Protocols of diagnosis and treatment are in continuous evolution and require evaluation of their results. OBJECTIVE: To review the clinical characteristics and results of a series of preterm-related posthemorrhagic hydrocephalus needing a definitive shunt from 1982 to 2020 in our institution. As a secondary objective we evaluated the safety of the changes in our protocol of treatment from 2015. METHODS: Retrospective review, clinical investigation. RESULTS: 133 patients were implanted a shunt in the study period. Shunt infection was diagnosed in 15 patients. Proximal shunt obstruction as the first complication was diagnosed in 30% of cases at one year, 37% at two years and 46% at five years. 61 patients developed very small or collapsed ventricles at last follow-up. Two thirds of our patients achieved normal neurological development or mild impairment. Changes in protocol did not significantly modify clinical results although improvement in most outcomes was observed. Mean follow-up was over nine years. CONCLUSIONS: Clinical outcomes are comparable to previous reported data. Changes in protocol proved to be safe and improved our results. Programmable shunts can be used safely in preterm patients although they may not prevent tendency towards ventricular collapse, which is very common after long follow-up.

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPG.co.

PURPOSE: To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. METHODS: We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. RESULTS: The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7-357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. CONCLUSIONS: Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity.

A deep learning model for prognosis prediction after intracranial hemorrhage.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is a common life-threatening condition that must be rapidly diagnosed and treated. However, there is still a lack of consensus regarding treatment, driven to some extent by prognostic uncertainty. While several prediction models for ICH detection have already been published, here we present a deep learning predictive model for ICH prognosis. METHODS: We included patients with ICH (n = 262), and we trained a custom model for the classification of patients into poor prognosis and good prognosis, using a hybrid input consisting of brain CT images and other clinical variables. We compared it with two other models, one trained with images only (I-model) and the other with tabular data only (D-model). RESULTS: Our hybrid model achieved an area under the receiver operating characteristic curve (AUC) of .924 (95% confidence interval [CI]: .831-.986), and an accuracy of .861 (95% CI: .760-.960). The I- and D-models achieved an AUC of .763 (95% CI: .622-.902) and .746 (95% CI: .598-.876), respectively. CONCLUSIONS: The proposed hybrid model was able to accurately classify patients into good and poor prognosis. To the best of our knowledge, this is the first ICH prognosis prediction deep learning model. We concluded that deep learning can be applied for prognosis prediction in ICH that could have a great impact on clinical decision-making. Further, hybrid inputs could be a promising technique for deep learning in medical imaging.

Reelin Protects against Colon Pathology via p53 and May Be a Biomarker for Colon Cancer Progression.

Previous observations made in human and mouse colons suggest that reelin protects the colon from pathology. In this study, we evaluated reelin expression during the transition from either colitis or precancerous lesions to colon cancer and tried to elucidate reelin regulation under these transition processes. Samples of healthy and pathological colons from humans and mice treated with either azoxymethane/dextran sulfate sodium (DSS) or azoxymethane alone were used. The relative abundances of reelin, DNMT-1 and ApoER2 mRNAs were determined by PCR in the colon samples cited above and in the tissue adjacent to mouse colon polyps and adenocarcinomas. In both, humans and mice, reelin mRNA abundance increased significantly in ulcerative colitis and slightly in polyps and decreased in adenomas and adenocarcinomas. Reelin expression was higher in the tissue adjacent to the colon adenocarcinoma and lower in the lesion itself. The reelin expression changes may result, at least in part, from those in DNMT-1 and appear to be independent of ApoER2. Lack of reelin downregulated p-Akt and p53 in healthy colon and prevented their increases in the inflamed colon, whereas it increased GSK-3ß in DSS-untreated mice. In conclusion, reelin mRNA abundance depends on the severity of the colon pathology, and its upregulation in response to initial injuries might prevent the beginning of colon cancer, whereas reelin repression favors it. Increased p53 expression and activation may be involved in this protection. We also propose that changes in colon reelin abundance could be used to predict colon pathology progression.

Acute Colon Inflammation Triggers Primary Motor Cortex Glial Activation, Neuroinflammation, Neuronal Hyperexcitability, and Motor Coordination Deficits.

Neuroinflammation underlies neurodegenerative diseases. Herein, we test whether acute colon inflammation activates microglia and astrocytes, induces neuroinflammation, disturbs neuron intrinsic electrical properties in the primary motor cortex, and alters motor behaviors. We used a rat model of acute colon inflammation induced by dextran sulfate sodium. Inflammatory mediators and microglial activation were assessed in the primary motor cortex by PCR and immunofluorescence assays. Electrophysiological properties of the motor cortex neurons were determined by whole-cell patch-clamp recordings. Motor behaviors were examined using open-field and rotarod tests. We show that the primary motor cortex of rats with acute colon inflammation exhibited microglial and astrocyte activation and increased mRNA abundance of interleukin-6, tumor necrosis factor-alpha, and both inducible and neuronal nitric oxide synthases. These changes were accompanied by a reduction in resting membrane potential and rheobase and increased input resistance and action potential frequency, indicating motor neuron hyperexcitability. In addition, locomotion and motor coordination were impaired. In conclusion, acute colon inflammation induces motor cortex microglial and astrocyte activation and inflammation, which led to neurons' hyperexcitability and reduced motor coordination performance. The described disturbances resembled some of the early features found in amyotrophic lateral sclerosis patients and animal models, suggesting that colon inflammation might be a risk factor for developing this disease.

Perturbing HIV-1 Ribosomal Frameshifting Frequency Reveals a cis Preference for Gag-Pol Incorporation into Assembling Virions.

HIV-1 virion production is driven by Gag and Gag-Pol (GP) proteins, with Gag forming the bulk of the capsid and driving budding, while GP binds Gag to deliver the essential virion enzymes protease, reverse transcriptase, and integrase. Virion GP levels are traditionally thought to reflect the relative abundances of GP and Gag in cells (∼1:20), dictated by the frequency of a -1 programmed ribosomal frameshifting (PRF) event occurring in gag-pol mRNAs. Here, we exploited a panel of PRF mutant viruses to show that mechanisms in addition to PRF regulate GP incorporation into virions. First, we show that GP is enriched ∼3-fold in virions relative to cells, with viral infectivity being better maintained at subphysiological levels of GP than when GP levels are too high. Second, we report that GP is more efficiently incorporated into virions when Gag and GP are synthesized in cis (i.e., from the same gag-pol mRNA) than in trans, suggesting that Gag/GP translation and assembly are spatially coupled processes. Third, we show that, surprisingly, virions exhibit a strong upper limit to trans-delivered GP incorporation; an adaptation that appears to allow the virus to temper defects to GP/Gag cleavage that may negatively impact reverse transcription. Taking these results together, we propose a "weighted Goldilocks" scenario for HIV-1 GP incorporation, wherein combined mechanisms of GP enrichment and exclusion buffer virion infectivity over a broad range of local GP concentrations. These results provide new insights into the HIV-1 virion assembly pathway relevant to the anticipated efficacy of PRF-targeted antiviral strategies. IMPORTANCE HIV-1 infectivity requires incorporation of the Gag-Pol (GP) precursor polyprotein into virions during the process of virus particle assembly. Mechanisms dictating GP incorporation into assembling virions are poorly defined, with GP levels in virions traditionally thought to solely reflect relative levels of Gag and GP expressed in cells, dictated by the frequency of a -1 programmed ribosomal frameshifting (PRF) event that occurs in gag-pol mRNAs. Herein, we provide experimental support for a "weighted Goldilocks" scenario for GP incorporation, wherein the virus exploits both random and nonrandom mechanisms to buffer infectivity over a wide range of GP expression levels. These mechanistic data are relevant to ongoing efforts to develop antiviral strategies targeting PRF frequency and/or HIV-1 virion maturation.

Fecal Volatile Organic Compounds and Microbiota Associated with the Progression of Cognitive Impairment in Alzheimer's Disease.

Metabolites produced by an altered gut microbiota might mediate the effects in the brain. Among metabolites, the fecal volatile organic compounds (VOCs) are considered to be potential biomarkers. In this study, we examined both the VOCs and bacterial taxa in the feces from healthy subjects and Alzheimer's disease (AD) patients at early and middle stages. Remarkably, 29 fecal VOCs and 13 bacterial genera were differentiated from the healthy subjects and the AD patients. In general, higher amounts of acids and esters were found in in the feces of the AD patients and terpenes, sulfur compounds and aldehydes in the healthy subjects. At the early stage of AD, the most relevant VOCs with a higher abundance were short-chain fatty acids and their producing bacteria, Faecalibacterium and Lachnoclostridium. Coinciding with the development of dementia in the AD patients, parallel rises of heptanoic acid and Peptococcus were observed. At a more advanced stage of AD, the microbiota and volatiles shifted towards a profile in the feces with increases in hexanoic acid, Ruminococcus and Blautia. The most remarkable VOCs that were associated with the healthy subjects were 4-ethyl-phenol and dodecanol, together with their possible producers Clostridium and Coprococcus. Our results revealed a VOCs and microbiota crosstalk in AD development and their profiles in the feces were specific depending on the stage of AD. Additionally, some of the most significant fecal VOCs identified in our study could be used as potential biomarkers for the initiation and progression of AD.

Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus.

Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant's demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.

Galectin-3 Deletion Reduces LPS and Acute Colitis-Induced Pro-Inflammatory Microglial Activation in the Ventral Mesencephalon.

Parkinson's disease is a highly prevalent neurological disorder for which there is currently no cure. Therefore, the knowledge of risk factors as well as the development of new putative molecular targets is mandatory. In this sense, peripheral inflammation, especially the originated in the colon, is emerging as a predisposing factor for suffering this disease. We have largely studied the pleiotropic roles of galectin-3 in driving microglia-associated immune responses. However, studies aimed at elucidating the role of galectin-3 in peripheral inflammation in terms of microglia polarization are lacking. To achieve this, we have evaluated the effect of galectin-3 deletion in two different models of acute peripheral inflammation: intraperitoneal injection of lipopolysaccharide or gut inflammation induced by oral administration of dextran sodium sulfate. We found that under peripheral inflammation the number of microglial cells and the expression levels of pro-inflammatory mediators take place specifically in the dopaminergic system, thus supporting causative links between Parkinson's disease and peripheral inflammation. Absence of galectin-3 highly reduced neuroinflammation in both models, suggesting an important central regulatory role of galectin-3 in driving microglial activation provoked by the peripheral inflammation. Thus, modulation of galectin-3 function emerges as a promising strategy to minimize undesired microglia polarization states.