Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association

There is considerable evidence that multiple sclerosis (MS) is an immune-mediated disease characterized by infiltration of inflammatory cells into the CNS and demyelination. Several myelin proteins may be encephalitogenic, including myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein (MOG), the latter being expressed on the external layer of myelin sheaths and hence accessible to antibody attack. We investigated MOG autoreactivity in serum and cerebrospinal fluid (CSF) by ELISA, employing the recombinant extracellular domain of MOG as antigen. We tested serum samples from 262 MS patients (175 relapsing-remitting, 43 primary progressive and 44 secondary progressive), 131 patients with other neurological diseases (OND) and 307 healthy controls. No patients or controls were receiving immunomodulating treatments. We found anti-MOG antibodies in the serum of 13.7% MS patients, mainly in those with secondary progressive MS (25%), in 13.7% of OND patients and in 6.2% of controls. We found a direct correlation (R(2) = 0.6, P = 0.002) between disease severity and anti-MOG titer only in patients with primary and secondary progressive MS. Anti-MOG antibodies were present in the CSF of 11.4% MS patients and 18.9% OND patients. Intrathecal synthesis of anti-MOG antibodies was demonstrated in four (4.5%) of MS patients and no OND patients. Anti-MOG antibodies are not specific for MS; however, they may characterize a subset of MS patients and this may be revealed by serial assays in relation to changing disease phase.     

Dissecting natural killer cell activation pathways through analysis of genetic mutations in human and mouse

Summary:  Natural killer (NK) cell cytotoxicity is mediated by multiple germ line-encoded activating receptors that recognize specific ligands expressed by tumor cells and virally infected cells. These activating receptors are opposed by NK inhibitory receptors, which recognize major histocompatibility complex class I molecules on potential targets, raising the threshold for NK cell activation. Once an abnormal cell has been detected, NK cells are the sentinel source of cytolytic mediators, such as granzymes and perforins, as well as interferon-γ, which can polarize the immune response to a T-helper 1 cell type. Activation signals are transmitted by adhesion-dependent pathways, immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathways, DAP10 ITAM-independent pathways, and by signaling through immunoreceptor tyrosine-based switch motifs. These pathways activate downstream signaling partners to trigger NK cell cytotoxicity. Some of these downstream molecules are unique to the various pathways, and some of these molecules are shared. Because of the complexity of signals involved in NK cell–target cell interaction, the generation of mice with targeted mutations in signaling molecules involved in adhesion, activation, or inhibition is essential for a precise dissection of the mechanisms regulating NK cell effector functions. Here we review recent advances in the genetic analysis of the signaling pathways that mediate NK cell killing.     

Matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinase-1 in patients with hypertension.

There are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase (MMP) system and their inhibitors (TIMPs) in human hypertension. The authors hypothesized that MMP-2, MMP-9, and TIMP-1 would be abnormal in hypertension, reflecting alterations in extracellular matrix (ECM) turnover. The authors measured plasma levels and activities of MMP-2, MMP-9, and TIMP-1 in 44 hypertensive patients and 44 controls. MMP-2 levels and activity were significantly higher in hypertensive group (p < .0001). Significant increase was also observed for MMP-9 level and activity (p < .0001) and for TIMP-1 (p < .0001) in hypertensive patients. Plasma levels and activities of MMP-2, MMP-9, and TIMP-1 are increased in hypertensive patients, which may reflect abnormal ECM metabolism.     

De novo engineering of reticular connective tissue in vivo by silk fibroin nonwoven materials

Biologically tolerated biomaterials are the focus of intense research. In this work, we examined the biocompatibility of three-dimensional (3D) nonwovens of sericin-deprived, Bombyx mori silk fibroin (SF) in beta-sheet form implanted into the subcutaneous tissue of C57BL6 mice, using sham-operated mice as controls. Both groups of mice similarly healed with no residual problem. Macroarray analysis showed that an early (day 3) transient expression of macrophage migration inhibitory factor (MIF) mRNA, but not of the mRNAs encoding for 22 additional proinflammatory cytokines, occurred solely at SF-grafted places, where no remarkable infiltration of macrophages or lymphocytes subsequently happened. Even an enduring moderate increase in total cytokeratins without epidermal hyperkeratosis and a transient (days 10-15) upsurge of vimentin occurred exclusively at SF-grafted sites, whose content of collagen type-I, after a delayed (day 15) rise, ultimately fell considerably under that proper of sham-operated places. By day 180, the interstices amid and surfaces of the SF chords, which had not been appreciably biodegraded, were crammed with a newly produced tissue histologically akin to a vascularized reticular connective tissue, while some macrophages but no lymphocytic infiltrates or fibrous capsules occurred in the adjoining tissues. Therefore, SF nonwovens may be excellent candidates for clinical applications since they both enjoy a long-lasting biocompatibility, inducing a quite mild foreign body response, but no fibrosis, and efficiently guide reticular connective tissue engineering.     

Indirect, across-the-midline retinotectal projections and representation of ipsilateral visual field in superior colliculus of the cat

1. In agreement with previous work, we have found that the ipsilateral visual field is represented in an extensive rostral portion--from one-third to one-half--of the superior colliculus (SC) of the cat. This representation is binocular. The SC representation of the ipsilateral visual field can be mediated both directly, by crossed retinotectal connections originating from temporal hemiretina, and indirectly, by across-the-midline connections relaying visual information from one-half of the brain to contralateral SC. 2. In order to study the indirect, across-the-midline visual input to the SC, we have recorded responses of SC neurons to visual stimuli presented to either the ipsilateral or the contralateral eye of cats with a midsagittal splitting of the optic chiasm. Units driven by the ipsilateral eye, presumably through the direct retinotectal input and/or corticotectal connections from ipsilateral visual cortex, were found throughout the SC, except at its caudal pole, which normally receives fibers from the extreme periphery of the contralateral nasal hemiretina. Units driven by the contralateral eye, undoubtedly through an indirect across-the-midline connection, were found only in the anterior portion of the SC, in which is normally represented the ipsilateral visual field. Receptive fields in both ipsilateral and contralateral eye had properties typical of SC receptive fields in cats with intact optic pathways. 3. All units having a receptive field in the contralateral eye had also a receptive field in the ipsilateral eye; for each of these units, the receptive fields in both eyes invariably abutted the vertical meridian of the visual field. The receptive field in one eye had about the same elevation relative to the horizontal meridian and the same vertical extension as the receptive field in the other eye; the two receptive fields of each binocular unit matched each other at the vertical meridian and formed a combined receptive field straddling the vertical midline of the horopter...     

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by ¹H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg⁻¹ i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.     

Effects of a Mediterranean Diet,Dairy, and Meat Products on Different Phenotypes of Dyslipidemia: A Preliminary Retrospective Analysis

Background: Dyslipidemia is one of the major causes of atherosclerotic cardiovascular disease (ASCVD) and a Mediterranean Diet (MD) is recommended for its prevention. The objectives of this study were to evaluate adherence to an MD at baseline and follow-up, in a cohort of dyslipidemic patients, and to evaluate how different food intakes can influence lipid profile, especially how different sources of saturated fatty acids impact lipid phenotype. Methods: A retrospective analysis was conducted on 106 dyslipidemic patients. Clinical characteristics, lipid profile, and food habits data were collected at baseline and after three months of follow-up with counseling. Adherence to an MD was evaluated with a validated food-frequency questionnaire (MEDI-LITE score). Results: The cross-sectional analysis showed that higher consumption of dairy products correlated independently with higher levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) and with lower triglycerides (TG) levels. Instead, lower HDL-C and TG levels and higher TC levels were independently associated with higher consumption of meat products. Adherence to an MD significantly improved after the follow-up period, from a mean value of 10 ± 3 (median 10, IQR 8–12) to 13 ± 2 (median 14, IQR 12–15), p < 0.0001. Conclusions: Dyslipidemic patients benefit from counseling for improving their adherence to an MD. The high intake of dairy products was associated with less atherogenic hyperlipidemia, which was characterized by higher levels of TC and HDL-C as compared withs the intake of an excessive amount of meat products, which was associated with higher levels of TC and TG and lower levels of HDL-C.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

A Cross-Country Network Analysis of Adolescent Resilience

PurposeIn situations of adversity, young people draw on individual, relational, and contextual (community and cultural) resources to foster their resilience. Recent literature defines resilience as a capacity that is underpinned by a network of interrelated resources. Although empirical studies show evidence of the value of a network approach, little is known regarding how different country contexts influence which resources are most critical within a resource network and how resources interact for adolescent resilience.MethodsNetwork analysis was conducted with data from studies that had used the Child and Youth Resilience Measure. Regularized partial correlation networks of 17 resources were estimated for 14 countries (Botswana, Canada, China, Colombia, Equatorial Guinea, India, Indonesia, Italy, Jordan, New Zealand, the Philippines, Romania, South Africa, and Syrian refugees living in Jordan). The sample size was 18,914 (mean age = 15.70 years, 48.8% female).ResultsWe observed mostly positive associations between the resources of interest. The salience and strength of associations between resources varied by country. The most central resource across countries was having supportive caregivers during stressful times because this resource had the most and strongest positive associations with other resources.ConclusionsThis study gives first empirical evidence from multiple countries that an interplay of social–ecological resources (such as individual skills, peer, caregiver and community support, and educational aspirations and opportunities) matter for adolescent resilience. Across countries, caregiver support appears to be most central for adolescent resilience. Future resilience interventions might apply this network approach to identify important, contextually relevant resources that likely foster additional resources.     

Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65–97) vs. 65 (51–75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.