Social cognition in multiple sclerosis: a 3-year follow-up {MRI} and behavioral study

Social cognition (SC) has become a topic of widespread interest in the last decade. SC deficits were described in multiple sclerosis (MS) patients, in association with amygdala lesions, even in those without formal cognitive impairment. In this 3-year follow-up study, we aimed at longitudinally investigating the evolution of SC deficits and amygdala damage in a group of cognitive-normal MS patients, and the association between SC and psychological well-being. After 3 years (T3) from the baseline examination (T0), 26 relapsing-remitting MS patients (RRMS) were retested with a neuropsychological battery and SC tasks (theory of mind, facial emotion recognition, empathy). A SC composite score (SCcomp) was calculated for each patient. Emotional state, fatigue, and quality of life (QoL) were also evaluated. RRMS patients at T3 underwent a 3T-MRI as performed at T0, from which were calculated both volume and cortical lesion volume (CLV) of the amygdalae. Compared to T0, at T3 all RRMS patients were still cognitive-normal and remained stable in their global SC impaired performance. At T0, SCcomp correlated with amygdala CLV (p = 0.002) while, at T3, was more associated with amygdala volume (p = 0.035) rather than amygdala CLV (p = 0.043). SCcomp change T3-T0 correlated with global emotional state (p = 0.043), depression (p = 0.046), anxiety (p = 0.034), fatigue (p = 0.025), and QoL-social functioning (p = 0.033). We showed the longitudinal stability of SC deficits in cognitive-normal RRMS patients, mirroring the amygdala structural damage and the psychological well-being. These results highlight that SC exerts a key role in M

Combination of ozone and activated carbon for Pharmaceuticals and Personal Care Products (PPCPs) removal in drinking water: influence of compounds characteristics and organic matter competition

The presence of Pharmaceuticals and Personal Care Products (PPCPs) in drinking water is raising concern for potential negative effects on human health. Ozonation and adsorption on activated carbon (AC) are the most promising processes for PPCPs removal among those usually present in drinking water treatment plants (DWTPs). To evaluate the performance of these processes, both individually and in combination, adsorption isotherms were determined on real matrices collected in a DWTP before and after ozonation, focusing on 10 PPCPs identified as the most critical for the analysed DWTP. AC showed higher PPCPs removals than ozonation, but the combination of the two processes was beneficial. However, the effect of ozone on adsorption depends on PPCPs reactivity with ozone. A competitive effect of organic matter on PPCPs adsorption was observed. Finally, the removal of absorbance at 254 nm is a good proxy variable for PPCPs removal

FFAs and QT intervals in obese women with visceral adiposity: Effects of sustained weight loss over 1 year

We evaluated 66 obese patients grouped by waist-to-hip ratio (WHR) into group A (WHR > 0.85, n = 30) and group B (WHR ≤ 0.85, n = 36), before and after 1 yr of diet-induced weight loss compared with 25 nonobese women. Before diet, the longest values of QT intervals and the highest levels of FFA and catecholamines were in group A (P < 0.01). In obese women (both groups), the corrected QT (QTc); interval correlated with plasma FFA (P < 0.01) and catecholamine (P < 0.02) concentrations. After 1 yr of diet, at the same levels of body weight reduction, the decrement of the QTc interval (P < 0.02), FFA (P < 0.01) and catecholamine (P < 0.02) levels were significantly greater in-group A than group B. In multivariate analysis, the decline of the QTc interval after weight loss was associated with changes in plasma FFA independently of changes in WHR and plasma catecholamines. Our data suggest that the QTc interval is tightly correlated with plasma FFA levels; shortening of cardiac repolarization times in the course of long-lasting weight reduction may reduce the risk of ventricular electrical instability, especially in women with abdominal adiposity

Fate of Pharmaceuticals and Personal Care Products (PPCPs) from discharge to drinking water: a modelling and monitoring integrated framework

Pharmaceuticals and Personal Care Products (PPCPs) presence in drinking water is gaining growing concern for potential negative effects on human health. This study combined modelling of river transport with monitoring campaigns performed over one year at a drinking water treatment plant (DWTP) located at the closure section of Po river basin, to evaluate the types of released PPCPs, their concentrations and fate in both the river and the DWTP. Over the 114 monitored PPCPs, maximum 23 compounds have been detected at the DWTP inlet with concentrations from 10 to 1800 ng/L, varying among PPCPs and in time. The transport in Po river of iopamidol, with the highest concentration at the DWTP inlet, was simulated combining hydrological and quality data and models. Finally, DWTP monitoring showed that ozonation and adsorption onto activated carbon have the main impact in reducing a wide variety of PPCPs, with performances influenced by their characteristics

CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis

INTRODUCTION AND METHODS: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis. RESULTS: PVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5 ng/mL) compared to both cognitively normal (10.9 ± 2.4, P = 0.049) and mild cognitive impaired (10.1 ± 2.9, P = 0.024) patients. CONCLUSIONS: CSF-PVALB levels reflect loss of cortical interneurons in MS patients with more severe disease course and might represent an early, new MS-specific biomarker of cortical neurodegeneration, atrophy, and cognitive decline

Fluorescein angiography findings in eyes with lamellar macular hole and epiretinal membrane foveoschisis

PURPOSE. The purpose of this paper was to study fluorescein angiography (FA) findings in eyes with lamellar macular hole (LMH), and epiretinal membrane (ERM) foveoschisis. METHODS. In this prospective, observational case series, 46 eyes of patients affected by either LMH or ERM foveoschisis were examined using optical coherence tomography (OCT) and FA. All patients underwent a comprehensive ophthalmological examination and a general workup to exclude uveitis. Main outcome measures were: presence of FA abnormalities, measurements of the areas of vascular leakage, and intensity of pixels in the vitreous. RESULTS. Twenty-four (52.2%) eyes with LMH and 22 (47.8%) with ERM foveoschisis were studied. Overall, FA abnormalities were found in 20 (83.3%) eyes with LMH and 18 (81.8%) with ERM foveoschisis. The median areas of posterior pole and peripheral leakage were 7.52 vs. 1.07 mm2 (P = 0.03) and 21.8 vs. 3.74 mm2 (P = 0.02) in the LMH and ERM foveoschisis group, respectively. Disk hyperfluorescence was found in 8 and 4 eyes and perivascular leak in 10 and 4 eyes with LMH and ERM foveoschisis, respectively. OCT-derived measurements of vitreous intensity did not differ between the two groups, and the investigational workup for uveitis was negative in all patients. CONCLUSIONS. Discrete areas of central and peripheral leakage are commonly found in eyes with LMH and ERM foveoschisis, whereas perivascular leak and hyperfluorescence of the disc are less frequently observed. These findings suggest that breakdown of the retinal blood barrier, involving the posterior pole and the periphery, is frequently associated with these two vitreoretinal disorders

Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : An Italian study

Background: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy. Methods: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients. Results: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes. Conclusions: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae

Antagonism of the complement component C4 by flavivirus nonstructural protein NS1

The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection