Prognostic significance of infarct size and location: The case of insular stroke

The prognostic relevance of strokes in different locations is debated. For example, insular strokes have been associated with increased mortality, but this association could reflect their greater severity. In two independent cohorts of patients with supratentorial ischemic stroke (n = 90 and 105), we studied the prognostic consequences of lesion size and location using voxel-based lesion-symptom mapping before and after volume control, which better accounts for total lesion volume. Strokes affecting the insula were larger than non-insular strokes (28 vs 2cc and 25 vs 3cc, p < 0.001 in both cohorts). A number of supratentorial areas (mainly in the left hemisphere), including the insula, were associated with poor functional outcome in both cohorts before (4014 voxels) and after volume control (1378 voxels), while the associations with death were greatly reduced after volume control (from 8716 to 325 voxels). Exploratory analyses suggested that the method of lesion volume quantification, the National Institutes of Health Stroke Scale hemispheric bias and patient selection can result in false associations between specific brain lesions and outcomes. In conclusion, death in the first months after stroke is mainly explained by large infarct volumes, whereas lesions of specific supratentorial structures, mostly in the left hemisphere, also contribute to poor functional outcomes

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker

Assessment of acute-phase protein response associated with the different pathological forms of bovine paratuberculosis

11 páginas, 1 tabla.In this study, the concentrations of two acute-phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were quantitatively assessed in serum samples from cattle naturally infected with paratuberculosis (PTB). APP profiles were compared across 190 animals classified according to the different pathological forms associated with infection: uninfected (n = 59), with focal lesions (n = 73), multifocal lesions (n = 19), and diffuse paucibacillary (n = 11) and diffuse multibacillary lesions (n = 28). Our results showed a significant increase in both APPs in infected animals compared to the control group, with differences depending on the type of lesion. Hp and SAA levels were increased significantly in all infected animals, except in cows with diffuse multibacillary lesions that showed similar values to non-infected animals. The expression pattern of both APPs was similar and negatively correlated with the antibody levels against PTB. These results indicate that the release of Hp and SAA is related to the presence of PTB lesions associated with a high cell-mediated immune response and a lower bacterial load, suggesting that the pro-inflammatory cytokines that are associated with these forms are the main stimulus for their synthesis. These molecules could show some potential to be used as putative biomarkers of PTB infection, particularly for the identification of subclinical animals showing pathological forms related to latency or resistance to the development of advanced lesions.This study was funded by grants RTI2018-099496-B-I00 from the Spanish Ministry of Science and Innovation and LE259/P18 from “Junta de Castilla y León”

The relationship between performance in a theory of mind task and intrinsic functional connectivity in youth with early onset psychosis

Psychotic disorders are characterized by theory of mind (ToM) impairment. Although ToM undergoes maturational changes throughout adolescence, there is a lack of studies examining ToM performance and its brain functional correlates in individuals with an early onset of psychosis (EOP; onset prior to age 18), and its relationship with age. Twenty-seven individuals with EOP were compared with 41 healthy volunteers using the "Reading-the-Mind-in-the-Eyes" Test, as a measure of ToM performance. A resting-state functional MRI scan was also acquired, in which the default mode network was used to identify areas relevant to ToM processing employing independent component analysis. Group effects revealed worse ToM performance and less intrinsic functional connectivity in the medial prefrontal cortex in EOP relative to healthy volunteers. Group by age interaction revealed age-positive associations in ToM task performance and in intrinsic connectivity in the medial prefrontal cortex in healthy volunteers, which were not present in EOP. Differences in ToM performance were partially mediated by intrinsic functional connectivity in the medial prefrontal cortex. Poorer ToM performance in EOP, coupled with less medial prefrontal cortex connectivity, could be associated with the impact of psychosis during a critical period of development of the social brain, limiting normative age-related maturation

Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms

Background: The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. Methods: One hundred twenty-eight individuals (33 SzO and 46 BpO, considered jointly as 'Familial High Risk' (FHR), and 49 controls) aged 6-17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2- and 4-year follow-up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow-up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume. Results: FHR participants who developed psychotic spectrum symptoms over time showed greater time-related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction. Conclusion: The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross-sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth

Critical review of technologies for the on-site treatment of hospital wastewater: From conventional to combined advanced processes

In this work, a raw and low cost mineral, ilmenite (FeTiO3), has been tested for the first time as a photocatalyst paired with peroxymonosulfate (HSO5-; PMS) for the inactivation of Enterococcus faecalis as an alternative to conventional treatments to disinfect wastewater for reuse. The influence of some operational parameters such as reagent dosage, catalyst concentration, initial pH, or flow rate was also studied and optimized. After several tests, the scarce pure photoactivity under UV-A was remarked by ilmenite because of its high iron content, which favors photogenerated charge recombination. However, ilmenite activity was highly promoted when combined with low concentrations of PMS and UV-A light, reaching total inactivation of Enterococcus faecalis in 120 min. Quenching tests were performed using methanol, tert-butyl alcohol, furfuryl alcohol, and Cu(II) to assess the main reactive species involved in the disinfection process determining the critical role of both HO·and SO4·- radicals in the process. Finally, the influence of the water matrix was also evaluated by studying the effect of water hardness and the presence of nutrients on the system. Overall, the PMS/Ilmenite/UV-A system yielded promising results with a total removal of Enterococcus faecalis in 120 min. However, it also showed the need for further study and understanding of the disinfection mechanism to achieve the same level of performance in real wastewaterThe "Comunidad de Madrid" supported this research through REMTAVARES S2013/MAE-2716 and S2018/EMT-434

Critical review of technologies for the on-site treatment of hospital wastewater: From conventional to combined advanced processes

This review aims to assess different technologies for the on-site treatment of hospital wastewater (HWW) to remove pharmaceutical compounds (PhCs) as sustances of emerging concern at a bench, pilot, and full scales from 2014 to 2020. Moreover, a rough characterisation of hospital effluents is presented. The main detected PhCs are antibiotics and psychiatric drugs, with concentrations up to 1.1 mg/L. On the one hand, regarding the presented technologies, membrane bioreactors (MBRs) are a good alternative for treating HWW with PhCs removal values higher than 80% in removing analgesics, anti-inflammatories, cardiovascular drugs, and some antibiotics. Moreover, this system has been scaled up to the pilot plant scale. However, some target compounds are still present in the treated effluent, such as psychiatric and contrast media drugs and recalcitrant antibiotics (erythromycin and sulfamethoxazole). On the other hand, ozonation effectively removes antibiotics found in the HWW (>93%), and some studies are carried out at the pilot plant scale. Even though, some families, such as the X-ray contrast media, are recalcitrant to ozone. Other advanced oxidation processes (AOPs), such as Fenton-like or UV treatments, seem very effective for removing pharmaceuticals, Antibiotic Resistance Bacteria (ARBs) and Antibiotic Resistance Genes (ARGs). However, they are not implanted at pilot plant or full scale as they usually consider extra reactants such as ozone, iron, or UV-light, making the scale-up of the processes a challenging task to treat high-loading wastewater. Thus, several examples of biological wastewater treatment methods combined with AOPs have been proposed as the better strategy to treat HWW with high removal of PhCs (generally over 98%) and ARGs/ARBs (below the detection limit) and lower spending on reactants. However, it still requires further development and optimisation of the integrated processes.Comunidad de Madri

Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

<p>Abstract</p> <p>Background</p> <p>Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia.</p> <p>Methods</p> <p>Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2.</p> <p>Results</p> <p>Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia.</p> <p>Conclusion</p> <p>Our results suggest that spermatozoa from asthenozoospermic patients present a reduced responsiveness to progesterone.</p

The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy

Nuevas terapias dirigidas para el tratamiento del cáncer

El cáncer es el término que se utiliza para englobar un conjunto de enfermedades que se caracterizan por el crecimiento descontrolado de células alteradas molecularmente por mutaciones o modificaciones epigenéticas.En la presente revisión describimos algunas terapias dirigidas que se están utilizando actualmente en clínic