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Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy morbidity and fetal loss caused by pathogenic autoantibodies directed against phospholipids (PL) and PL-cofactors. Isolated neurological APS may represent a significant diagnostic challenge, as epidemiological, clinical and neuroimaging features may overlap with those of multiple sclerosis (MS). In an open view, MS could be considered as an organ-specific anti-lipid (phospholipid and glycosphingolipid associated proteins) disease, in which autoreactive B cells and CD8+ T cells play a dominant role in its pathophysiology. In MS, diverse autoantibodies against the lipid-protein cofactors of the myelin sheath have been described, whose pathophysiologic role has not been fully elucidated. We carried out a review to select clinical studies addressing the prevalence of antiphospholipid (aPL) autoantibodies in the so-called MS-like syndrome. The reported prevalence ranged between 2% and 88%, particularly aCL and aβ2GPI, with predominant IgM isotype and suggesting worse MS prognosis. Secondarily, an updated summary of current knowledge on the pathophysiological mechanisms and events responsible for these conditions is presented. We draw attention to the clinical relevance of diagnosing isolated neurological APS. Prompt and accurate diagnosis and antiaggregant and anticoagulant treatment of APS could be vital to prevent or at least reduce APS-related morbidity and mortality.

Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic fields in quickening wound repair processes and tissue regeneration. The clinical use of extremely low-frequency electromagnetic fields could represent a novel frontier in tissue repair and oral health, with an interesting clinical perspective. The present study aimed to evaluate the effect of an extremely low-frequency sinusoidal electromagnetic field (SEMF) and an extremely low-frequency pulsed electromagnetic field (PEMF) with flux densities of 1 mT on a model of oral healing process using gingival fibroblasts. An in vitro mechanical injury was produced to evaluate wound healing, migration, viability, metabolism, and the expression of selected cytokines and protease genes in fibroblasts exposed to or not exposed to the SEMF and the PEMF. Interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-&beta, ), metalloproteinase 2 (MMP-2), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and heme oxygenase 1 (HO-1) are involved in wound healing and tissue regeneration, favoring fibroblast proliferation, chemotaxis, and activation. Our results show that the exposure to each type of electromagnetic field increases the early expression of IL-6, TGF-&beta, and iNOS, driving a shift from an inflammatory to a proliferative phase of wound repair. Additionally, a later induction of MMP-2, MCP-1, and HO-1 was observed after electromagnetic field exposure, which quickened the wound-healing process. Moreover, electromagnetic field exposure influenced the proliferation, migration, and metabolism of human gingival fibroblasts compared to sham-exposed cells. This study suggests that exposure to SEMF and PEMF could be an interesting new non-invasive treatment option for wound healing. However, additional studies are needed to elucidate the best exposure conditions to provide the desired in vivo treatment efficacy.

Exposure to environmental extremely low-frequency electromagnetic fields (ELF-EMF) in everyday life is increasing and it is a matter of great debate whether exposure to ELF-EMF can be harmful to human health. The neuropathology and symptoms of neurodegenerative disease depends on factors other than genetic predispositions, such as environmental exposure to disease-related risk factors. Research focusing on a possible contribution of ELF-EMF to cell injury and to the development of neurodegenerative disorders is characterized by conflicting data from epidemiological and animal studies. Due to lack of a direct link between neurodegenerative processes and ELF-EMF exposure, our goal was to investigate if ELF-EMF exposure may represent a possible risk factor. In the present study, using neuronal-like SH-SY5Y neuroblastoma cells, we show that the balance between generation and elimination of reactive oxygen species, as well as the balance between pro- and anti-inflammatory cytokines linked to oxidative stress, was maintained ensuring that cells respond properly to ELF-EMF (50Hz /1mT). In SH-SY5Y-exposed cells we observed increased intracellular 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio reflecting the rate of transmitter synthesis, catabolism and release, while matrix metalloproteinases that play critical roles in neuronal cell death were not significantly altered. The results presented here indicate that changes caused by short (1h-3h) and sub-chronic (48 h) exposure to 50Hz/1mT ELF-EMF in SH-SY5Y cells are minor in comparison to the neuronal cell damage expected to underlie neurodegeneration or cognitive impairment. Thus, these results are in accord with epidemiological studies that have provided little support for a link between ELF-EMFs and neurodegeneration.

This article has come about from two considerations: on one hand, living together in a work environment is becoming more and more challenging; on the other, training professionals at work represents a used and relevant action incentive in order to support and improve individual, group, and organizational development. In light of the fact that organizations are asking more and more complex questions, this work aims at developing a reflection on how adopting a certain perspective and educational method is particularly suitable to support the organization to achieve substantial outcomes, such as developing generative living and working together in organizations. In this article, we will analyze two illustrative cases, underlining evolution and learning process with a particular focus on the consequences of living and working together in organizations.

Organisational welfare is a complex private system that offers advantages to a company and its employees. However, when occupational welfare is largely implemented as an “economic” strategy, there is a high probability that it would not necessarily be capable of guaranteeing a profit. The risks and possibilities associated with the implementation of a welfare programme incur further challenges if applied to the context of SMEs. Thus, SMEs are organisational realities characterised by specific emotional and relational dynamics. As such, welfare in these realities takes on deep value and significance and so it potentially impacts processes of valorising human resources. With our study, we analysed welfare practices and representations within specific organisational realities (SMEs) in order to understand how welfare could impact organisational processes of valorising human resources. Based on our results, we realised that welfare can be seen as a sort of magnifying glass that allowed for the detection of the themes that led the organisations to reflect on their rooted values and identities. We suggest that SMEs should think about welfare as a process rather than a product, strengthening their awareness of factors, dynamics and processes that define the complexity of the quality of life in organisations.

This study investigated the anti-inflammatory effects of novel pseudotripeptides (GPE 1–3) as potential candidates to counteract neuroinflammation processes in Alzheimer’s disease. GPE 1–3 pseudotripeptides are synthetic derivatives of Gly- l -Pro- l -Glu (GPE), the N-terminal tripeptide of IGF-1, obtained through the introduction of isosteres of the amidic bond (aminomethylene unit) to increase the metabolic stability of the native tripeptide. The results showed that all synthetic derivatives possessed higher half-lives (t1/2 > 4 h) than GPE (t1/2 = 30 min) in human plasma and had good water solubility. The biological results demonstrated that GPE 1–3 had protective properties in several experimental models of treated THP-1 cells. Notably, the novel pseudotripeptides influenced inflammatory cytokine expression (IL-1β, IL-18, and TNF-α) in Aβ25–35-, PMA-, and LPS-treated THP-1 cells. In PMA-differentiated THP-1 macrophages, both GPE 1 and GPE 3 reduced the expression levels of all selected cyto-chemokines, even though GPE 3 showed the best neuroprotective properties.

BackgroundMultiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing–remitting (RR) form, characterized by flare-ups followed by periods of recovery. Many inflammatory and anti-inflammatory cytokines have been proposed as backers in MS pathogenesis, and the balance between these differing cytokines can regulate MS severity. Interferon (IFN)-β, a current disease-modifying therapy for MS, has demonstrated beneficial effects in reducing disease severity in MS patients. However, its immunoregulatory and anti-inflammatory actions in MS are not wholly understood. The aim of the study was to define, in clinically stable patients with RR-MS, the serum concentration of several cytokines, canonical or not, and their modulation by IFN-β therapy.MethodsRelapsing–remitting-MS patients were enrolled and diagnosed according to revised Mc Donald Diagnostic Criteria. A set of cytokines [including non-canonical neurotransmitter acetylcholine (ACh) and adipokines] and B-cell differentiation molecules, as potential biomarkers, were evaluated in 30 non-treated RR-MS patients compared to 30 IFN-β-treated MS patients and 30 age, gender, and body mass index-matched healthy controls (HC).ResultsNaïve MS patients showed significantly higher levels of interleukin (IL)-1β, IL-12/IL-23p40, IL-18, high-mobility group box protein-1, and IL-18 binding protein (IL-18BP) than MS-treated patients (p

Introduction Environmental, behavioural and psychological stimuli can activate inflammation. Psychosocial factors such as work demands and decision latitude, social support, and psychological distress, play important roles in the development of inflammatory status. We conducted a study on occupational stress and its influence on cytokines homeostasis in Italian offshore oil installation workers. Methods Enrolled workers from an offshore oil company were divided into two groups, which took rotations of four weeks to work on the platforms at sea. The onshore and offshore groups were broadly the same in terms of their ranking, work experience, age, and distribution of job categories. All subjects complete a self- administered questionnaire collecting information on socio-demographic characteristics, occupational stress, sleep disorders, and past injuries. The salivary cortisol and serum cytokines levels were measured by ELISA, cytokines gene expression was evaluated by Real-time PCR. Results Salivary cortisol concentrations were significantly increased confirming the effectiveness of occupational stress. In fact, in our workers, cortisol level was directly correlated to job insecurity, State-Trait Anxiety (STAI-1), shift work and inversely proportional to sleep quality. In addition, we observed a direct correlation also between BMI and cortisol level. A significant increase of TNFa and a weak elevation of IL-10 level were observed in the offshore group. To examine whether changes in cytokines levels were due to changes in cell type composition, a reduction of ratio between lymphocyte percentages and neutrophils percentages (Ly/Ne%) were observed. Spontaneous expression of IL-1b, TNFa and IL-10 were higher in offshore respect to onshore workers. The increase in all PHA-induced cytokine release was significantly higher in the offshore workers. Only TNFa was significantly higher in LPS-stimulated PBMC of offshore workers. Conclusion Taken together, the current study revealed that occupational stress not only activates neuroendocrine stress systems, but also influence cytokines homeostasis.

Over the years - due to the aging population, the process of corporatisation and a demand for a higher quality of services - professionals who work in Care Homes have been exposed to an increasing risk of physical and emotional malaise because of the number of challenges they've been asked to manage. Given these factors, there is a growing interest in the study and understanding of professions in geriatric care settings. In the literature there is a prevalence of quantitative studies offering an overview in terms of indicators - at the individual or group or organizational level - concerning the potential development of situations of professional malaise. Conversely, there is a lack of qualitative studies exploring the risk and protection factors. For this reason, in this study we decided to use a qualitative approach to explore "more up close" this kind of organizational context and to keep together the different levels in systemic terms in order to identify - according to professionals' perceptions - resource factors (in order to leverage these aspects) and fatigue factors (to identify them and treat them). Three Italian Care Homes were involved and the interview's sample was composed of 45 professionals - 15 nurses, 30 total Patient Care Assistants (PCAs) and Auxiliary Care Assistants (ACAs), of these, 17 males and 28 females, with an average age of 43 years (SD = 0.78) - selected using a sampling of maximum variability. From the analysis of the materials there seem to be four profiles of the professionals involved. Implications to ensure a functional human resource management are discussed for the purpose of promote the well-being of the various professionals, and, as a result, an increasing quality of service.

Multiple Sclerosis (MS) is an autoimmune disease, having not fully understood aetiology, and both genetic and environmental factors contribute to the pathogenesis of the disease. The cholinergic system has been indicated as a mediator of neuro-immune interactions, as well as an internal regulator of immune responses. The aim of the present research was to assess the associations between BChE and AChE genetic variations and serum cholinergic and inflammatory profiles in 102 Relapsing Remitting-MS patients and 117 healthy controls. An increased frequency of the BChE K-allele in MS patients as compared to controls was found. In addition, data showed that patients had higher BChE enzymatic activity, which is increased by the presence of the polymorphic allele and reduced amounts of circulating ACh. AChE polymorphism was significantly associated to reduced activity in both patients and controls. We propose that serum BChE and AChE activity may be used as a secondary markers to assess the role of non-neuronal cholinergic system in regulating peripheral inflammation via ACh regulation. This pilot study shed light on the role of the non-neuronal cholinergic system in immune cells to better understand MS pathogenesis. The cross-talk between the periphery and the CNS could have a new undescribed crucial role for MS, regarded as a systemic disease.

In view of the deep crisis affecting Italian prisons and the urgent need to review the sense and meaning of this institution, initiatives promoting innovative custodial and rehab practices are incr...

Change has always been a delicate and complex process for people, groups, and organizations that experience it. This work, starting with a reorganization process that involved a Lombard penitentiar...

Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p &lt, 0.001) and IL-1β expression (p &lt, 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p &lt, 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.

The social productive environment has changed rapidly generating new opportunities and challenges for individuals, groups, and organizations. The school-world is affected by these general changes and also subject to constant specific pressure (e.g. reforms, resources reallocation, precariousness, increasinglycomplex demands).In this scenario teachers play a crucial role.The research aims at investigating which are resources and efforts perceived by teachers and how these influence their wellbeing or malaise.We explored teachers’ professional histories and their perception of their work group and work context(s).A phenomenological approach was adopted;50 high-school teachers were involved; semi-structured interviews and the “Professional Life-Space Drawing” were used; content analysis and a descriptive-phenomenological analysis of Drawings were conducted. Results permit the description of different professional situations.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

Increasing evidence suggests that elevated production and/or reduced clearance of amyloid- β peptide (A β ) drives the early pathogenesis of Alzheimer’s disease (AD). A β soluble oligomers trigger a neurotoxic cascade that leads to neuronal dysfunction, neurodegeneration and, ultimately, clinical dementia. Inflammation, both within brain and systemically, together with a deficiency in the neurotransmitter acetylcholine (ACh) that underpinned the development of anticholinesterases for AD symptomatic treatment, are invariable hallmarks of the disease. The inter-relation between A β, inflammation and cholinergic signaling is complex, with each feeding back onto the others to drive disease progression. To elucidate these interactions plasma samples and peripheral blood mononuclear cells (PBMCs) were evaluated from healthy controls (HC) and AD patients. Plasma levels of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and A β were significantly elevated in AD vs. HC subjects, and ACh showed a trend towards reduced levels. A β challenge of PBMCs induced a greater release of inflammatory cytokines interleukin-1 β (IL-1 β ), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF- α) from AD vs. HC subjects, with IL-10 being similarly affected. THP-1 monocytic cells, a cell culture counterpart of PBMCs and brain microglial cells, responded similarly to A β as well as to phytohaemagglutinin (PHA) challenge, to allow preliminary analysis of the cellular and molecular pathways underpinning A β-induced changes in cytokine expression. As amyloid- β precursor protein expression, and hence A β , has been reported regulated by particular cytokines and anticholinesterases, the latter were evaluated on A β- and PHA-induced chemocytokine expression. Co-incubation with selective AChE/BuChE inhibitors, (-)-phenserine (AChE) and (-)-cymserine analogues (BuChE), mitigated the rise in cytokine levels and suggest that augmentation of the cholinergic anti-inflammatory pathway may prove valuable in AD.

The work aims at presenting the contribution of the professional life space drawing (DSSVP), a graphic-symbolic tool, to the analysis of the identities within the working frameworks. Namely, the study will consider police officers and middle management working in a prison (casa circondariale) in Lombardia (Italy). Firstly, the relationship between work and identity and the challenges that it is facing in the present setting will be considered. Secondly, the analysis will focus on the prisons context, where the professionals figures investigated within this study operate. At this stage, the tool of DSSVP will be presented together with those issues that it has helped to highlight thanks to a metric-type and phenomenological analysis Il lavoro intende presentare il contributo che il Disegno Simbolico dello Spazio di Vita Professionale (DSSVP), uno strumento grafico-simbolico, puo portare nello studio delle identita entro i contesti di lavoro. In particolare nello studio si fara riferimento ad agenti e quadri intermedi, che lavorano in una Casa Circondariale lombarda. Ci si soffermera dapprima sull’evoluzione del rapporto lavoro-identita e sulle sfide che questa ultima e chiamata ad affrontare nello scenario odierno. A seguire, dopo aver delineato il contesto delle Case circondariali, entro cui i professionisti considerati in questo lavoro operano, verra presentato lo strumento del DSSVP e cio che riesce a mettere in evidenza grazie a un’analisi di tipo metrico e di tipo fenomenologico.

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis.

Objectives In our previous reports, we have demonstrated that extremely low-frequency electromagnetic fields (ELF-EMF) exposure enhances the proliferation of keratinocyte. The present study aimed to clarify effects of ELF-EMF on wound healing and molecular mechanisms involved, using a scratch in vitro model. Materials and methods The wounded monolayer cultures of human immortalized keratinocytes (HaCaT), at different ELF-EMF and Sham exposure times were monitored under an inverted microscope. The production and expression of IL-1β, TNF-α, IL-18 and IL-18BP were measured by enzyme-linked immunosorbent assay and quantitative real-time PCR. The activity and the expression of matrix metalloproteinases (MMP)-2/9 was evaluated by zymography and Western blot analysis, respectively. Signal transduction proteins expression (Akt and ERK) was measured by Western blot. Results The results of wound healing in vitro assay revealed a significant reduction of cell-free area time-dependent in ELF-EMF-exposed cells compared to Sham condition. Gene expression and release of cytokines analysed were significantly increased in ELF-EMF-exposed cells. Our results further showed that ELF-EMF exposure induced the activity and expressions of MMP-9. Molecular data showed that effects of ELF-EMF might be mediated via Akt and ERK signal pathway, as demonstrated using their specific inhibitors. Conclusions Our results highlight ability of ELF-EMF to modulate inflammation mediators and keratinocyte proliferation/migration, playing an important role in wound repair. The ELF-EMF accelerates wound healing modulating expression of the MMP-9 via Akt/ERK pathway.

The work we present has a double purpose: sketching some thinking guidelines to overcome the typical Sicilian Mafia mindset and, at the same time, helping to reinforce the theoretical–methodological paradigm of group analysis by means of a dialogue with the concept of relational good. In this framework of dialogue and confrontation, since psychical, social, and economic developments influence each other, they can determine a strong repercussion in the social context of individuals. Relational good thus becomes not only an interdisciplinary intersection, but also a tool that can significantly help fulfilling suitable programs of local development.

Microbiota play a key role in various body functions, as well as in physiological, metabolic, and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Evidence indicates that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that reside on the mucosal surface or within the mucus layer interact with the host immune system, thus, a healthy gut microbiota is essential for the development of mucosal immunity. In patients with human immunodeficiency virus (HIV), including those who control their disease with antiretroviral drugs (ART), the gut microbiome is very different than the microbiome of those not infected with HIV. Recent data suggests that, for these patients, dysbiosis may lead to a breakdown in the gut’s immunologic activity, causing systemic bacteria diffusion and inflammation. Since in HIV-infected patients in this state, including those in ART therapy, the treatment of gastrointestinal tract disorders is frustrating, many studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition, and microbial translocation. This mini-review analyzed the use of probiotics to prevent and attenuate several gastrointestinal manifestations and to improve gut-associated lymphoid tissue (GALT) immunity in HIV infection.

This work aims at thoroughly studying a phenomenon that today is still not really discussed (i.e., the criminal organization called ‘Ndrangheta). We will particularly deal with the culture and organizational structure of this Mafia phenomenon and analyze its new territories of infiltration and domination (the region of Lombardy, in Northern Italy) after its migration from its original territory (the region of Calabria in Southern Italy). From the review of the existing literature on ‘Ndrangheta, we can actually point out that the contributions on the theme deal with the Mafia phenomenon, circumscribing it in its original territory, therefore mostly adopting a sociological and historical viewpoint. Up to today, nobody addressed ‘Ndrangheta outside these territorial boundaries and adopting a psychological viewpoint, which is the one this contribution starts from. In more specific terms, a text is analyzed, which is composed by the reports of the pre-trial detention order called Crimine-Infinito [Endless Cri...

Literature underscores the complex role of coaches in sport organizations, especially in youth sectors. Their need for support, not only on the technical level, is emerging. In recent years an interesting international debate has evolved regarding what education is most suitable to support coach development. The article intends to enter this debate by proposing an educational model for youth soccer coaches. This educational proposal is the outcome of reflection that originated from various experiences with about 110 Italian youth soccer coaches over the past six years. The first part is dedicated to a review of the literature on coaching education, and the second to the educational model presented (e.g., theoretical background, characteristics, setting, outcomes, and considerations regarding the management of this educational process). The strength of this model was precisely to have put some recurrent issues in dialogue with the specific organizational contexts in which the educational programs were impl...

Increasing evidence suggests that the early pathogenesis of Alzheimer’s disease (AD) is driven by elevated production and/or reduced clearance of amyloid-β peptide (Aβ), which is derived from the larger Aβ precursor protein (APP). Aβ aggregates to form neurotoxic soluble oligomers that trigger a cascade of events leading to neuronal dysfunction, neurodegeneration and, ultimately, clinical dementia. Inflammation, both within the brain and systemically, together with a deficiency in the brain neurotransmitter acetylcholine, which underpinned the development of anticholinesterases for the symptomatic treatment of AD, are invariable hallmarks of the disease. The inter-relation between Aβ, inflammation and cholinergic signaling is complex, with each feeding back onto the others to drive disease progression. To elucidate these interactions plasma samples and peripheral blood mononuclear cells (PBMCs) were evaluated from healthy control (HC) subjects and AD patients. Plasma levels of acetyl- (AChE) and butyrylcholinesterase (BuChE) as well as Aβ were significantly elevated in AD vs. HC subjects, and acetylcholine showed a trend towards reduced levels. Aβ challenge of the AD and HC PBMCs resulted in greater release of inflammatory cytokines interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) from AD vs. HC subjects, with IL-10 expression being similarly affected. THP-1 monocytic cells, a cell culture counterpart of PBMCs and brain microglial cells, responded similarly to Aβ as well as to phytohaemagglutinin (PHA) challenge, to allow preliminary analysis of the cellular and molecular pathways that underpin Aβ-induced changes in cytokine expression. In light of prior studies demonstrating that APP expression was regulated by specific cytokines and anticholinesterase drugs, the latter were evaluated on Aβ- and PHA-induced chemo-cytokine expression. Co-incubation with selective inhibitors, such as the acetylcholinesterase (AChE)-inhibitor (−)-phenserine and the butyrylcholinesterase (BuChE)-inhibitor (−)-cymserine analogues mitigated the rise in cytokine levels, and suggest that augmentation of the cholinergic anti-inflammatory pathway may prove valuable in AD.

The work highlights one of the direct stakeholders of RSA organization, the caregivers of patients with Alzheimer. It studies if and in which measure the caregivers’ level of health are strongly influenced by their perceived Relational Quality of the retirement homes in which their loved ones are hospitalized. Participants were 111 caregivers of patients with a diagnosis of dementia and recovered in RSA since at least 6 months. The study measures if the relational quality perceived by caregivers has a positive and direct influence on two mood states of caregivers: depression-dejection, anger-hostility. It also investigates if the protective function of relational quality remains significant also in presence of moderator variable such as social support and burden. The analysis confirms that increasing perceived relational quality corresponds to a decreased perception of caregivers’ discomfort humoral. The social support factor does not act as moderator, but it is confirmed the moderator role of burden. The research work provided some important empirical about the important role of caregivers retirement homes. They represent an emotional and relational link that connects the guest on one hand with the familiar net and on the other hand with the service operators. Therefore caregiver is a central resource, who needs protection and valorisation.

Gastrointestinal stromal tumours (GISTs) represent the most common non-epithelial mesenchymal tumours of the gastrointestinal tract. The role of the pathologist in the differential diagnosis of GISTs, as well as the correct understanding of these neoplasia by detailed clinicopathologic, biological and genetic studies, are becoming increasingly important in optimizing the management of these tumours and to develop new therapies for the treatment of advanced diseases.

Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs) on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz) on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2(-), which were countered by compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a decline in CAT activity and a rise in O2(-) levels. Together these studies support the further evaluation of ELF-EMF exposure in cellular and in vivo preclinical models to define mechanisms potentially impacted in humans.

Low frequency (LF) electromagnetic fields (EMFs) are abundantly present in modern society and in the last 20 years the interest about the possible effect of extremely low frequency (ELF) EMFs on human health has increased progressively. Epidemiological studies, designed to verify whether EMF exposure may be a potential risk factor for health, have led to controversial results. The possible association between EMFs and an increased incidence of childhood leukemia, brain tumors or neurodegenerative diseases was not fully elucidated. On the other hand, EMFs are widely used, in neurology, psychiatry, rheumatology, orthopedics and dermatology, both in diagnosis and in therapy. In vitro studies may help to evaluate the mechanism by which LF-EMFs affect biological systems. Invitro model of wound healing used keratinocytes (HaCaT), neuroblastoma cell line (SH-SY5Y) as a model for analysis of differentiation, metabolism and functions related to neurodegenerative processes, and monocytic cell line (THP-1) was used as a model for inflammation and cytokines production, while leukemic cell line (K562) was used as a model for hematopoietic differentiation. MCP-1, a chemokine that regulates the migration and infiltration of memory T cells, natural killer (NK), monocytes and epithelial cells, has been demonstrated to be induced and involved in various diseases. Since, varying the parameters of EMFs different effects may be observed, we have studied MCP-1 expression in HaCaT, SH-SY5Y, THP-1 and K562 exposed to a sinusoidal EMF at 50 Hz frequency with a flux density of 1 mT (rms). Our preliminary results showed that EMF-exposure differently modifies the expression of MCP-1 in different cell types. Thus, the MCP-1 expression needs to be better determined, with additional studies, with different parameters and times of exposure to ELF-EMF.

Background: Loop Electrosurgical Excision Procedure (LEEP) represents the mainstay technique for CIN2+ removal. The major concern in conservative treatment is to verify whether CIN eradication was complete, since incomplete excision is associated with an increased risk of cervical cancer. The histopathologic evaluation of resection margins status is far from perfect, since cervical lesions may recur in 5-15% of patients who had conisation specimens with clean margins. Current follow-up protocol of patients treated by conisation for high grade CIN is manly based on the combination of cytology-plus- HPV-DNA testing. This approach showed high sensitivity but low specificity level in detecting recurrence. The consequence were overdiagnosis and overtreatment, especially in youngest women, in which spontaneous regression rate of CIN is substantial. In this longitudinal study we investigated whether patient’s age, cone depth and pre-conisation HPV-load level, may be used as predictive markers for residual/recurrent CIN after conisation. Then we aimed to examined the role of E6/E7 mRNA testing during post-conization follow-up. Methods: The study, focused on the outcome of 116 patients treated for CIN by LEEP, included three consecutive steps. Firstly, the authors analysed the prevalence of residual/recurrence disease after conization; then, they investigated which factors may influence treatment failure even when resection margins were clean; finally, they evaluated the diagnostic accuracy of E6/E7 mRNA test as predictive marker of recurrence. Results: HPV infection was detected in 31% of patients at 6-month follow-up and in 11.2% of patients, at 24-month follow-up. Younger women showed higher rate of recurrence than older ones. The risk of residual/recurrent infection did not correlate with cone-depth. Recurrence is higher in patients with low viral load level than in those having high load levels. mRNA test showed higher specificity and positive predictive value than the combination cytology-plus-HPV-DNA test. Conclusion: The inclusion of mRNA test within the current protocol of follow-up would efficiently and earlier predict the risk of residual/ recurrent cervical abnormalities after conisation. This molecular strategy would also reduce overtreatment, particularly in patients above 30 years of age.

Acetylcholine (ACh) has been the first molecule to be identified as neurotransmitter. The cholinergic and cholinoceptive areas, both in central and peripheral nervous system, have been well documented. Acetylcholine has been described to control, during embryogenesis, cell proliferation as well as neuron and glial cell survival and differentiation. In the adult, acetylcholine and its receptors are distributed in many tissues other than in the nervous system. More recently, new physiological roles in neuronal and non-neuronal tissues have been proposed for ACh as well as its possible involvement in different pathologies. Altered levels of ACh or modified receptors expression and function, in selected areas of the nervous system, have been described in several neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington as well as in psychiatric disorders such as schizophrenia. Frequently own cognitive, behavioral and motor disabilities that characterize these pathologies are correlated to cholinergic circuit dysfunction. Moreover the involvement of ACh as modulator of the inflammation, in and out of the nervous system, has suggested that its altered functions might represent an additional pathogenetic mechanism negatively influencing the disease outcome as recently suggested in multiple sclerosis. The present review will focus on identifying the cause/effect relationship that may explain the cholinergic dysfunction in several nervous system disorders. Moreover the possible therapeutic novelties including cholinesterase inhibitors, muscarinic agonists and antagonists, and genetic therapy will be discussed.