Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive–compulsive disorder (OCD) and Tourette's syndrome (TS)

There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold

A Research Publication on the Economic Value of the Third Sector in Italy

The crisis of the welfare state as we have known it in Italy and Europe over the last few decades has forced countries and the societies of those so-called "advanced countries" to review their priorities and the methods by which social services are provided. In this way a process has begun, which reflects on how to support the organization of a renewed sense of civic responsibility, able to satisfy demand and requirements where the Public and the Market, for various reasons, are not able to provide an adequate response. The entire sector, according to the information gathered during the 8th General Census of Industry and Services carried out by Istat (the National Institute for Statistics) in 2001, adjusted in the 2003 annual report, includes: 2 5,232 non-profit institutions, equal to 5.4% of all institutional units; approximately 488,000 employees and independent workers, equal to 2.5% of all assigned workers; approximately 4 million individuals involved as volunteers 38 billion in revenue (over 3.3% of the GDP); 35 billion in costs, with a surplus of 3 billion reinvested in the activities carried out. These figures will obviously need to be updated following the growth in the world of non-profits over the last decade, but they are even more significant when accompanied by a calculation of the social savings deriving from the labour hours provided free of charge by the four million volunteers and, even more so, the material and immaterial well-being provided to those who benefited from their work, their help and their compassion. In 2012, in cooperation with IPSOS and UniCredit's Territorial Research and Strategies, UniCredit Foundation promoted and carried out an investigation into the economic value of the third sector in Italy. The study looks at the situation in the Italian non-profit sector and the growth trends registered by the sector in recent years

The Transcriptional Repressor hDaxx Potentiates p53-dependent Apoptosis

p53 and its homologues p73 and p63 are transcription factors that play an essential role in modulating cell cycle arrest and cell death in response to several environmental stresses. The type and intensity of these responses, which can be different depending on the inducing stimulus and on the overall cellular context, are believed to rely on the activation of defined subsets of target genes. The proper activation of p53 family members requires the coordinated action of post-translational modifications and interaction with several cofactors. In this study, we demonstrate that the multifunctional protein hDaxx interacts with p53 and its homologues, both in vitro and in vivo, and modulates their transcriptional activity. Moreover, we show that hDaxx, which has been implicated in several apoptotic pathways, increases the sensitivity to DNA damage-induced cell death and that this effect requires the presence of p53. Although hDaxx represses p53-dependent transcription of the p21 gene, it does not affect the activation of proapoptotic genes, and therefore acts by influencing the balance between cell cycle arrest and proapoptotic p53 targets. Our results therefore underline the central role of hDaxx in modulating the apoptotic threshold upon several stimuli and identify it as a possible integrating factor that coordinates the response of p53 family members

Food insecurity in families with children under five years of age on the Brazil-Peru Amazon border

Food and nutrition security is the regular and permanent access to quality food in sufficient quantity. The aim of this study was to estimate the prevalence and factors associated with food insecurity in households with children under five in the Amazon frontier Brazil - Peru. The study was conducted in 352 households in Assis Brasil (Brazil) and 89 households Iñapari (Peru), finding a prevalence of food insecurity of 40.6 % and 38.2 % , respectively ( p = 0.856 ) . In Assis Brasil, having domicile with wood floors or land increased by 2.47 times the odds of food insecurity compared to cement fl oors, ceramic or quarry tiles . Belonging to the poorest tertile increased the chance of food insecurity in 6.04 times ( p < 0.001 ), and the increment of each new resident increased by 37 % the chance of food insecurity in the household . In Iñapari, only living in house made of wood or with a wood floor was associated with food insecurity, showing that income is still the main factor associated with food insecurity in the Amazonian borders

Inflammation and neutrophil extracellular traps in cerebral cavernous malformation

Correction: Volume79, Issue7 Article Number: 388 DOI: 10.1007/s00018-022-04418-8Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3(iECKO)), we show that endothelial cells from Ccm3(iECKO) mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3(iECKO) mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3(iECKO) mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas of patients with CCM confirms the clinical relevance of NETs in CCM.Peer reviewe

Luminal Plasma Treatment for Small Diameter Polyvinyl Alcohol Tubular Scaffolds

Plasma-based surface modification is recognized as an effective way to activate biomaterial surfaces, and modulate their interactions with cells, extracellular matrix proteins, and other materials. However, treatment of a luminal surface of a tubular scaffold remains non-trivial to perform in small diameter tubes. Polyvinyl alcohol (PVA) hydrogel, which has been widely used for medical applications, lacks functional groups to mediate cell attachment. This poses an issue for vascular applications, as endothelialization in a vascular graft lumen is crucial to maintain long term graft patency. In this study, a Radio Frequency Glow Discharges (RFGD) treatment in the presence of NH3 was used to modify the luminal surface of 3-mm diameter dehydrated PVA vascular grafts. The grafted nitrogen containing functional groups demonstrated stability, and in vitro endothelialization was successfully maintained for at least 30 days. The plasma-modified PVA displayed a higher percentage of carbonyl groups over the untreated PVA control. Plasma treatment on PVA patterned with microtopographies was also studied, with only the concave microlenses topography demonstrating a significant increase in platelet adhesion. Thus, the study has shown the possibility of modifying a small diameter hydrogel tubular scaffold with the RFGD plasma treatment technique and demonstrated stability in ambient storage conditions for up to 30 days

Predictive and prognostic significance of telomerase levels/telomere length in tissues and peripheral blood in head and neck squamous cell carcinoma.

A growing body of evidence indicates that the expression of TERT, the catalytic subunit of telomerase, is a biological marker of progression in several cancers. We investigated the predictive and prognostic role of TERT levels and telomere length in tissues and peripheral blood in patients with head and neck squamous cell carcinoma (HNSCC). High TERT levels in cancer tissues were independently associated with worse response to therapy (odds ratio [OR]:6.26), regional failure (hazard ratio [HR]:5.75), progression (HR:2.12), and death (HR:3.53). Longer telomeres in the mucosa surrounding the tumor (SM) were independently associated with a lower risk of mucosal failure (HR:0.39). While telomere length in peripheral blood mononuclear cells (PBMC) significantly decreased with age, no correlation was found between age and telomere length in SM. No associations were found between TERT levels in plasma and telomere length in PBMC and the prognostic variables. High levels of TERT transcripts in cancer cells represent a reliable prognostic marker for identifying HNSCC patients with risk of progression. The altered relationship of telomere length to age in SM compared with PBMC suggests that in a subset of cases the phenotypically normal SM constitutes an acquired telomere-shortened epithelial field prone to genetic instability

CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>Granulocytes generally exert protective roles in the central nervous system (CNS), but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE), the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined.</p> <p>Methods</p> <p>CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and <it>in situ </it>hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques.</p> <p>Results</p> <p>CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS) or pertussis toxin (PTX), the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease.</p> <p>Conclusions</p> <p>This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.</p

An Intense and Short-Lasting Burst of Neutrophil Activation Differentiates Early Acute Myocardial Infarction from Systemic Inflammatory Syndromes

BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis

Impairment of circulating endothelial progenitors in Down syndrome

<p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p