Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing-remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. METHODS: To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties. RESULTS: We found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. IL-9 induced activation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 and reduced the expression of activation markers, such as CD45, CD14, CD68, and CD11b in inflammatory macrophages stimulated in vitro with lipopolysaccharide and interferon (IFN)-γ. Similarly, in situ the number of activated CD68+ macrophages was significantly reduced in areas with high levels of IL-9. Moreover, in the same conditions, IL-9 increased the secretion of the anti-inflammatory cytokine, transforming growth factor (TGF)-β. CONCLUSIONS: These results reveal a new cytokine expressed in the CNS, with a role in the context of MS. We have demonstrated that IL-9 and its receptor are both expressed in CNS. Moreover, we found that IL-9 decreases the activation state and promotes the anti-inflammatory properties of human macrophages. This mechanism may contribute to the beneficial effects of IL-9 that are observed in MS, and may be therapeutically potentiated by modulating IL-9 expression in MS

Access to Mental Health Care during the First Wave of the COVID-19 Pandemic in Italy: Results from the COMET Multicentric Study

The COVID-19 pandemic represents an unprecedented public health emergency, with consequences at the political, social, and economic levels. Mental health services have been called to play a key role in facing the impact of the pandemic on the mental health of the general population. In the period March-May 2020, an online survey was implemented as part of the Covid Mental Health Trial (COMET), a multicentric collaborative study carried out in Italy, one of the Western countries most severely hit by the pandemic. The present study aims to investigate the use of mental health resources during the first wave of the pandemic. The final sample consisted of 20,712 participants, mainly females (N = 14,712, 71%) with a mean age of 40.4 ± 14.3 years. Access to mental health services was reported in 7.7% of cases. Among those referred to mental health services, in 93.9% of cases (N = 1503 subjects) a psychological assessment was requested and in 15.7% of cases (N = 252) a psychiatric consultation. People reporting higher levels of perceived loneliness (OR 1.079, 95% CI 1.056-1.101, p < 0.001), practicing smart-working (OR 1.122, 95% CI 0.980-1.285, p = 0.095), using avoidant (OR 1.586, 95% CI 1.458-1.725, p < 0.001) and approach (OR 1.215, 95% CI 1.138-1.299, p < 0.001) coping strategies more frequently accessed mental health services. On the other hand, having higher levels of perceived social support (OR 0.833, 95% CI 0.795-0.873, p < 0.001) was associated with a reduced probability to access mental health services. The COVID-19 pandemic represents a new threat to the mental health and well-being of the general population, therefore specific strategies should be implemented to promote access to mental healthcare during the pandemic and afterwards

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants

The effect of social media and infodemic on mental health during the COVID-19 pandemic: results from the COMET multicentric trial

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8 &amp; PLUSMN; 0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2 &amp; PLUSMN; 0.1 h vs. 4.9 &amp; PLUSMN; 0.02; p &lt; 0.005). According to the multivariate logistic regression model, the risk of excessive use of social media and Internet was significantly higher in people with moderate levels of depressive symptoms (OR: 1.26, CI 95%: 0.99 to 1.59, p &lt; 0.0.005); while protective factors were being students (OR: 0.72, CI 95%: 0.53 to 0.96, p &lt; 0.0029) and living in central Italy (OR: 0.46, CI 95%: 0.23 to 0.90, p &lt; 0.002). The evaluation of social media and Internet use by the general population represents a first step for developing specific protective and supportive interventions for the general population, including practical suggestions on how to safely use Internet and social media

Upper- and mid-mantle interaction between the Samoan plume and the Tonga-Kermadec slabs

Mantle plumes are thought to play a key role in transferring heat from the core\u2013mantle boundary to the lithosphere, where it can significantly influence plate tectonics. On impinging on the lithosphere at spreading ridges or in intra-plate settings, mantle plumes may generate hotspots, large igneous provinces and hence considerable dynamic topography. However, the active role of mantle plumes on subducting slabs remains poorly understood. Here we show that the stagnation at 660 km and fastest trench retreat of the Tonga slab in Southwestern Pacific are consistent with an interaction with the Samoan plume and the Hikurangi plateau. Our findings are based on comparisons between 3D anisotropic tomography images and 3D petrological-thermo-mechanical models, which self-consistently explain several unique features of the Fiji\u2013Tonga region. We identify four possible slip systems of bridgmanite in the lower mantle that reconcile the observed seismic anisotropy beneath the Tonga slab (VSH4VSV) with thermo-mechanical calculations

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

A Multicenter Clinical Evaluation of Data Logging in Cochlear Implant Recipients Using Automated Scene Classification Technologies

Currently, there are no studies assessing everyday use of cochlear implant (CI) processors by recipients by means of objective tools. The Nucleus 6 sound processor features a data logging system capable of real-time recording of CI use in different acoustic environments and under various categories of loudness levels. In this study, we report data logged for the different scenes and different loudness levels of 1,366 CI patients, as recorded by SCAN. Monitoring device use in cochlear implant recipients of all ages provides important information about the listening conditions encountered in recipients' daily lives that may support counseling and assist in the further management of their device settings. The findings for this large cohort of active CI users confirm differences between age groups concerning device use and exposure to various noise environments, especially between the youngest and oldest age groups, while similar levels of loudness were observed

Значение мотивации персонала на предприятии

Основная цель – систематизировать сведения о мотивации персонала и его значении на предприятии

Evaluation of a text supported weight maintenance programme ‘Lighten Up Plus’ following a weight reduction programme: randomised controlled trial

Background Many overweight people find it difficult to maintain weight loss after attending a weight reduction programme. Self-weighing and telephone support are known to be useful methods for self-monitoring for weight loss. We examined the effectiveness of an SMS-text messaging based weight maintenance programme to encourage regular self-weighing in adults who had completed a 12 week commercial weight loss programme. Methods Randomised controlled trial of 380 obese or overweight men and women. The intervention group (n=190) received a single maintenance support phone call and SMS-text based weight maintenance messages over 12 weeks to encourage regular self-weighing after completing their weight loss programme. The primary outcome was change in weight at nine months follow up. Results Our sample (N=380) had a mean age of 47.4 years (SD 13.4), mean baseline weight and BMI of 93.1kg (16.1) and 34.4 kg/m2 (5.0) respectively, as well as majority female (87.3%) and White British (80.0%). Using intention to treat analysis both groups regained weight at nine months follow up; the intervention group regained an average of 1.36 kg while the control group regained 1.81 kg. Adjusting for covariates resulted in a mean difference of 0.45 kg (95% CI -0.78, 1.67) favouring the intervention group at nine month follow up. Conclusions We found no evidence that an SMS based weight maintenance intervention encouraging adults to weigh themselves weekly prevented weight regain at three or nine months after completing a commercial weight loss programme. <br/