Development of p-Tau Differentiated Cell Model of Alzheimer's Disease to Screen Novel Acetylcholinesterase Inhibitors.

Alzheimer's disease (AD) is characterized by an initial accumulation of amyloid plaques and neurofibrillary tangles, along with the depletion of cholinergic markers. The currently available therapies for AD do not present any disease-modifying effects, with the available in vitro platforms to study either AD drug candidates or basic biology not fully recapitulating the main features of the disease or being extremely costly, such as iPSC-derived neurons. In the present work, we developed and validated a novel cell-based AD model featuring Tau hyperphosphorylation and degenerative neuronal morphology. Using the model, we evaluated the efficacy of three different groups of newly synthesized acetylcholinesterase (AChE) inhibitors, along with a new dual acetylcholinesterase/glycogen synthase kinase 3 inhibitor, as potential AD treatment on differentiated SH-SY5Y cells treated with glyceraldehyde to induce Tau hyperphosphorylation, and subsequently neurite degeneration and cell death. Testing of such compounds on the newly developed model revealed an overall improvement of the induced defects by inhibition of AChE alone, showing a reduction of S396 aberrant phosphorylation along with a moderate amelioration of the neuron-like morphology. Finally, simultaneous AChE/GSK3 inhibition further enhanced the limited effects observed by AChE inhibition alone, resulting in an improvement of all the key parameters, such as cell viability, morphology, and Tau abnormal phosphorylation.

Interferon regulatory factor 5 is a potential target of autoimmune response triggered by Epstein-barr virus and Mycobacterium avium subsp. paratuberculosis in rheumatoid arthritis: investigating a mechanism of molecular mimicry.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease characterised by a pro-inflammatory cytokines linked erosive joint damage and by humoral and cellular response against a broad range of self-peptides. Molecular mimicry between Epstein-Barr virus (EBV), Mycobacterium avium subsp. paratuberculosis (MAP) and host peptides has long been regarded as an RA pathogenetic mechanism. Using bioinformatic analysis we identified high sequence homology among interferon regulatory factor 5 (IRF5), EBV antigen BOLF1 and MAP antigen MAP_4027. Our objective was to evaluate the presence in sera of RA patients of antibodies (Abs) directed against human homologous IRF5 cross-reacting with BOLF1 and MAP_4027. METHODS: Frequency of reactivity against IRF5424-434, BOLF1305-320 and MAP_402718-32 was tested by indirect ELISA in sera from 71 RA patients and 60 healthy controls (HCs). RESULTS: RA sera show a remarkable high frequency of reactivity against IRF5424-434 in comparison to HCs (69% vs. 8%; p<0.0001). Similarly, seroreactivity against BOLF1305-320 was more frequently detected in RA sera than in HCs counterpart (58% vs. 8%; p<0.0001). Frequency of Abs against MAP_402718-32 was 17% in RA sera vs. 5% in HCs with a p-value at the threshold level (p<0.051). Prevalence of Abs against at least one of the assessed epitopes reached 72% in RA patients and 15% among HCs. Levels of Abs in RA patients were significantly related to systemic inflammation. CONCLUSIONS: IRF5 is a potential autoimmune target of RA. Our results support the hypothesis that EBV and MAP infections may be involved in the pathogenesis of RA, igniting a secondary immune response that cross-reacts against RA self-peptides.

Delivery of written and verbal information on healthcare-associated infections to patients: opinions and attitudes of a sample of healthcare workers.

BACKGROUND: Patients education is considered a valuable mean to prevent and control healthcare-associated infections (HAIs). This cross-sectional study aims to assess declared practices of healthcare workers (HCWs) regarding the delivery of information about HAIs to patients. METHODS: A 14-item multiple-choice questionnaire was designed to assess the attitudes and declared practices of HCWs (physicians, nurses and nursing assistants). Between October 2012 and October 2013, we surveyed a sample of HCWs from 4 acute hospitals in Piedmont (North-western Italy). Written information was available at three hospitals (A, B and C) and verbal information at the last one (hospital D). RESULTS: We surveyed 288 HCWs (79 physicians, 124 nurses and 85 healthcare assistants). At hospital A, B and C, 128 (71.6%) HCWs declared that written information was usually delivered to any patient and 145 (66.5%) that nurses usually delivered it. Only 42 (26.3%) of them - 97.6% nurses -declared that they usually delivered written information to patients. Among all surveyed HCWs, 210 (72.9%) declared that patients also receive verbal information on HAI - mainly by nurses (70.8%) and physicians (50%) - but only 88 (29,2%) - 23.8% physician and 48.8% nurses - declared that they usually informed patients. Finally, 83 (27.7%) HCWs believed that they should decide whether or not to deliver information to patient case by case. CONCLUSIONS: A formal policy requiring to deliver written information is most likely not enough to induce HCWs to better inform patients about HAIs. Health Trusts might introduce more target actions to reinforce HCWs' practices, such as training and internal auditing.

The no correlation argument: can the morality of conscientious objection be empirically supported? the Italian case.

BACKGROUND: The legitimacy of conscientious objection to abortion continues to fuel heated debate in Italy. In two recent decisions, the European Committee for Social Rights underlined that conscientious objection places safe, legal, and accessible care and services out of reach for most Italian women and that the measures that Italy has adopted to guarantee free access to abortion services are inadequate. Nevertheless, the Ministry of Health states that current Italian legislation, if appropriately applied, accommodates both the right to conscientious objection and the right to voluntary abortion. MAIN BODY: One empirical argument used to demonstrate that conscientious objection does not create barriers to abortion is the "no correlation" argument, which the Italian Committee for Bioethics employed to demonstrate that no association exists between conscientious objection and waiting times for voluntary abortion in Italy and to support the weak form of conventional comprise adopted by the Italian legislation to balance the conflict between women' autonomy and healthcare professionals' moral integrity. Conversely, we showed how the "no correlation" argument fails to demonstrate the absence of a relationship between the number of conscientious objectors and waiting times for voluntary abortion, and that the limitations of the "no correlation" argument itself demonstrate how it is still difficult to describe the real effect of conscientious objection on the access to abortion services and to evaluate the suitability of conventional compromise to effectively balance conflicting moral principles. CONCLUSION: Further studies are needed to better describe the relationship between conscientious objection and waiting times for voluntary abortion. If new evidence would show that the increasing proportion of objectors does undermine the efficacy of the Italian law and the right of a woman to freely obtain a voluntary abortion, new ways will need to be found to address the conflict between moral principles and restrict the protection accorded to the principle of moral integrity. This would inevitably imply the need to constrain and to redefine the terms and conditions for claiming conscientious objection.

Conscientious objection and waiting time for voluntary abortion in Italy.

OBJECTIVES: This study sought to determine whether a correlation exists in Italy between conscience-based refusal by physicians to perform an abortion and waiting times for elective abortion. METHODS: Data on the number of objectors and of elective abortions performed within different time intervals were retrieved from annual Italian ministerial reports. Spearman's correlation coefficients were calculated between an indicator of the increase in workload for non-objectors when conscientious objection is exercised by physicians refusing to provide an abortion and the proportion of women whose request for an abortion was met within 14 days, or later, in 13 regions in Italy. RESULTS: An inverse correlation emerged between the workload for non-objectors and the proportion of abortions performed within 14 days of the request in seven regions (statistically significant in Emilia-Romagna and Tuscany). There was a direct correlation between increased workload and the proportion of abortions performed later than 21 days in nine regions. The same trends were highlighted at national level. CONCLUSIONS: Our results suggest that when data spanning at least more than a decade are available, a trend toward an inverse correlation can be noted between the workloads for non-objectors and timely access to elective abortion. This holds organisational and ethical implications.

Decoding the Microbiome's Influence on Rheumatoid Arthritis.

The aim is better to understand and critically explore and present the available data from observational studies on the pathogenetic role of the microbiome in the development of rheumatoid arthritis (RA). The electronic databases PubMed, Scopus, and Web of Science were screened for the relevant literature published in the last ten years. The primary outcomes investigated included the influence of the gut microbiome on the pathogenesis and development of rheumatoid arthritis, exploring the changes in microbiota diversity and relative abundance of microbial taxa in individuals with RA and healthy controls (HCs). The risk of bias in the included literature was assessed using the GRADE criteria. Ten observational studies were identified and included in the qualitative assessment. A total of 647 individuals with RA were represented in the literature, in addition to 16 individuals with psoriatic arthritis (PsA) and 247 HCs. The biospecimens comprised fecal samples across all the included literature, with 16S rDNA sequencing representing the primary method of biological analyses. Significant differences were observed in the RA microbiome compared to that of HCs: a decrease in Faecalibacterium, Fusicatenibacter, Enterococcus, and Megamonas and increases in Eggerthellales, Collinsella, Prevotella copri, Klebsiella, Escherichia, Eisenbergiella, and Flavobacterium. There are significant alterations in the microbiome of individuals with RA compared to HCs. This includes an increase in Prevotella copri and Lactobacillus and reductions in Collinsella. Collectively, these alterations are proposed to induce inflammatory responses and degrade the integrity of the intestinal barrier; however, further studies are needed to confirm this relationship.

Availability of emergency contraception: a survey of hospital emergency department gynaecologists and emergency physicians in Piedmont, Italy.

OBJECTIVES: To compare the knowledge and the willingness of emergency physicians and gynaecologists caring for women in Italian emergency departments (EDs) to prescribe levonorgestrel-only emergency contraceptive pills (LNG-EC pills). METHODS: A cross-sectional survey was conducted in 2009; anonymous postal questionnaires were mailed to the medical staff working at the 30 EDs located in Piedmont (Italy). RESULTS: Emergency physicians and gynaecologists have similar knowledge of the pharmacokinetics and pharmacodynamics of LNG-EC pills, but do not feel at ease in prescribing these and consider the prescription of LNG-EC pills an inappropriate activity for ED staff. CONCLUSIONS: In Italy, unlike in most other European countries, LNG-EC pills are still prescription drugs. Thus it may be useful to further investigate the reasons why Italian ED medical staff do not feel the prescription of LNG-EC pills should be within their remit and whether women can successfully obtain the prescription from physicians working in other services that can be accessed around the clock.

An Overview of Strategies to Improve Vaccination Compliance before and during the COVID-19 Pandemic.

The debate on vaccination mandate was fuelled over the past two years by the COVID-19 pandemic. This study aimed at overviewing vaccination strategies and corresponding vaccine coverages for childhood vaccinations before the pandemic and for SARS-CoV-2 in high-income countries. A qualitative comparison was also performed between the two contexts: unlike for childhood vaccinations, only one European country (Austria) imposed generalised COVID-19 mandates, most countries preferring targeted mandates for higher-risk categories (Italy, Greece) or workers in key public services (Finland, Australia, New Zealand, UK, Germany). Many countries (Norway, Sweden, Netherlands, Portugal, Spain) confirmed their traditional voluntary vaccination approach also for COVID-19, while others (Slovenia and Hungary), historically relying on compulsory vaccination strategies, surprisingly opted for voluntary SARS-CoV-2 vaccination, with unsatisfactory results in terms of immunisation rates. However, no tangible relationship was generally found between vaccination policies and immunisation coverages: data show that, unlike some countries with mandates, countries where vaccinations are merely recommended could achieve higher coverages, even beyond the recommended 95% threshold. The COVID-19 experience has enriched pre-existent vaccination strategy debates by adding interesting elements concerning attitudes towards vaccines in a novel and unexplored context. Interpreting the available results by considering the different cultural contexts and vaccine hesitancy determinants can help to better understand the complexity of the relationship between policies and achieved coverages.

Sexual Harassments Related to Alcohol and Drugs Intake: The Experience of the Rape Centre of Turin.

A cross-sectional study was conducted that describes the characteristics of sexual violence episodes related to the intake of alcohol and drugs observed among women that turned to the "Centro Soccorso Violenza Sessuale" (SVS) of the Sant'Anna Hospital in Turin between 1 January 2008, and 31 December 2017. Two hundred twenty-two patients were enrolled, 25 of which were minors, 141 were Italians, and most of them knew their aggressor and were raped in a private home. One hundred and fifty-five of them declared to the healthcare personnel to have taken alcoholic substances and/or drugs in conjunction with the event (86 reported having drunk alcohol, 36 having taken drugs and 33 disclosed both alcohol and drug abuse). If the woman knew her abuser, alcohol consumption was described as voluntary in more than 80% of cases, while in relation to drugs the consumption was equally voluntary or fraudulent. About 73% of women who reported having drunk alcohol just had amnesia or amnesia related to other symptoms, while amnesia was present in about 63% of women who reported only drug use. Physicians observed physical injuries on 156 women. Patients who reported to have assumed alcohol presented a significantly higher risk to suffer any physical injury and have a significantly increased risk to suffer injuries to their head and/or neck. The results obtained underline how even in Northern Italy alcohol intake represents the most widespread psychoactive substance in case of drug-facilitated sexual assault. There is therefore a need to promote education and prevention campaigns among citizens, especially among the youngest.

HERV-K Envelope Protein Induces Long-Lasting Production of Autoantibodies in T1DM Patients at Onset in Comparison to ZNT8 Autoantibodies.

Human endogenous retroviruses (HERVs) have been thought of as silent passengers within our genomes, but their reactivation has been linked with several autoimmune diseases, including type 1 diabetes (T1DM). In order to evaluate the potential role of HERVs, in addition to the recognized role of HERV-W, we focused on the debated role of the HERV-K family in T1DM. Therefore, we performed a serological evaluation of IgG antibodies against HERV-K Env epitope (HERV-K Env19−37) in comparison to an important ß-cellular autoimmunity biomarker, ZnT8, from plasma samples of Sardinian children at the onset of T1DM, different T1DM groups (1−5 and 6−12 years since diagnosis), and healthy controls (HCs), by an indirect enzyme-linked immunosorbent assay (ELISA). A significant antibody response was observed against HERV-K Env19−37 (p < 0.0001) in T1DM patients compared to HCs, and significantly higher IgG responses were detected in the group at the onset compared to the other T1DM groups and HCs. Unlike the trend of the ß-cellular autoimmunity autoantibodies, for HERV-K Env antibodies we observed positive values that persist over time up to 5 years since the onset of T1DM. Our results add new evidence about the presence of antibodies against HERV-K in T1DM, but further investigations are necessary to relate these results with the established role of HERVs, considering the contrasting results for HERV-K.

Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients.

BACKGROUND/OBJECTIVE: Chronic humoral immune response against multiple microbial antigens may play a crucial role in the etiopathogenesis of rheumatoid arthritis (RA). We aimed to assess the prevalence and magnitude of antibody response against various bacterial and viral immunogen peptides in the sera of RA patients compared with the general population. METHODS: Polyclonal IgG antibodies (Abs) specific for peptides derived from Porphyromonas gingivalis (RgpA, Kpg), Aggregatibacter actinomycetemcomitans (LtxA1, LtxA2), Mycobacterium avium subsp. paratuberculosis (MAP4027), Epstein-Barr virus (EBNA1, EBVBOLF), and human endogenous retrovirus (HERV-W env-su) were detected by ELISA in serum samples from 148 consecutive RA patients and 148 sex and age-matched healthy controls (HCs). In addition, the presence of a relationship between the positivity and the titer of antibodies and RA descriptors was explored by bivariate correlation analysis. RESULTS: RA patients exhibit a higher prevalence of humoral immune response against all tested peptides compared to HCs with a statically significant difference for MAP4027 (30.4% vs. 10.1%), BOLF (25.7% vs. 8.1%), RgpA (24.3% vs. 9.4%), HERV W-env (20.3% vs. 9.4%), and EBNA1 (18.9% vs. 9.4%) peptides. Fifty-three (35.8%) out of 148 RA serum and 93 (62.8%) out of 148 HCs were negative for all pathogen-derived peptides. There was a significant correlation between OD values obtained by ELISA test against all peptides (p < 0.0001). We also found an increased titer and prevalence of Abs against LtxA1 and LtxA2 in seropositive vs. seronegative RF (p = 0.019, p = 0.018). CONCLUSION: This study demonstrates a significantly increased humoral response against multiple pathogens in patients with RA and implies that they could be an important factor in the pathogenesis of the disease. Therefore, the role of each individual pathogen in RA needs to be further investigated.

In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disease characterized by disrupted memory, learning functions, reduced life expectancy, and locomotor dysfunction, as a result of the accumulation and aggregation of amyloid peptides that cause neuronal damage in neuronal circuits. In the current study, we exploited a transgenic Drosophila melanogaster line, expressing amyloid-ß peptides to investigate the efficacy of a newly synthesized acetylcholinesterase inhibitor, named XJP-1, as a potential AD therapy. Behavioral assays and confocal microscopy were used to characterize the drug effect on AD symptomatology and amyloid peptide deposition. The symptomatology induced in this particular transgenic model recapitulates the scenario observed in human AD patients, showing a shortened lifespan and reduced locomotor functions, along with a significant accumulation of amyloid plaques in the brain. XJP-1 treatment resulted in a significant improvement of AD symptoms and a reduction of amyloid plaques by diminishing the amyloid aggregation rate. In comparison with clinically effective AD drugs, our results demonstrated that XJP-1 has similar effects on AD symptomatology, but at 10 times lower drug concentration than donepezil. It also showed an earlier beneficial effect on the reduction of amyloid plaques at 10 days after drug treatment, as observed for donepezil at 20 days, while the other drugs tested have no such effect. As a novel and potent AChE inhibitor, our study demonstrates that inhibition of the enzyme AChE by XJP-1 treatment improves the amyloid-induced symptomatology in Drosophila, by reducing the number of amyloid plaques within the fruit fly CNS. Thus, compound XJP-1 has the therapeutic potential to be further investigated for the treatment of AD.

HERV-K Modulates the Immune Response in ALS Patients.

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19-37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19-37 and HERV-K env 109-126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109-126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19-37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.

Violence against pregnant women in the experience of the rape centre of Turin: Clinical and forensic evaluation.

Pregnant women can be victims of violence: as a matter of fact, far from being a protective factor, pregnancy can trigger or worsen episodes of abuse. Studies conducted by the WHO highlight that its incidence fluctuates between 1% and 28%. Therefore violence during pregnancy is endemic all over the world and involves all social strata. We analysed 113 medical records concerning pregnant women (average age 27.9 ± 6.0 years, 80 foreigners), who turned to the Centro Soccorso Violenza Sessuale, one of the two Italian Rape Centre, in Turin between January 1st, 2005 and December 31st, 2017. Fifty-three women were visited in the first trimester, 41 in the second, and 16 in the third, while 3 during the puerperium. The current partner was accused to be the abuser by the 84.4% of the Italian women and by the 69.2% of the foreigners. Sixty-eight women suffered multiple forms of violence, while 98 suffered only physical violence, and 3 reported only sexual abuse. According to 20 women, violent episodes increased during pregnancy. The clinical history of these women was characterized by some recurrent physical symptoms, such as pelvic pain, abdominal pain, facial pain and headache and 54 women presented injuries (abrasions and ecchymosis). Our results confirm that violence in pregnancy is a social and public health problem. Therefore it is important that the health personnel should be prepared not only to care for women seeking help, but above all its better preparation could also identify victims of violence, which do not report abuse.

Role of Infections in the Pathogenesis of Rheumatoid Arthritis: Focus on Mycobacteria.

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by chronic erosive polyarthritis. A complex interaction between a favorable genetic background, and the presence of a specific immune response against a broad-spectrum of environmental factors seems to play a role in determining susceptibility to RA. Among different pathogens, mycobacteria (including Mycobacterium avium subspecies paratuberculosis, MAP), and Epstein-Barr virus (EBV), have extensively been proposed to promote specific cellular and humoral response in susceptible individuals, by activating pathways linked to RA development. In this review, we discuss the available experimental and clinical evidence on the interplay between mycobacterial and EBV infections, and the development of the immune dysregulation in RA.

IL-2 and Mycobacterial Lipoarabinomannan as Targets of Immune Responses in Multiple Sclerosis Patients.

Interleukin 2 (IL-2) is considered a key player in exacerbating multiple sclerosis (MS). Therapies targeting its receptor have been developed; however, a resolution of the disease and side effects are still an issue of concern. The involvement of other factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) and envelope protein derived from human endogenous retrovirus type W (HERV-Wenv), in MS pathogenesis has been recently suggested. Here, we investigated the levels of antibodies (Abs) directed against IL-2 and HERV-Wenv in 108 MS patients, 34 patients affected by neuromyelitis optica spectrum disorder (NMOSD), and 137 healthy controls (HCs). Our results show increased levels of Abs specific to IL-2 and HERV-Wenv-su antigens in MS vs. HCs (p < 0.0001 for IL-2, p = 0.0004 for HERV-Wenv) and significantly decreased levels in NMOSD vs. MS. The assessment of different 12-month-long therapies on Abs against IL-2, HERV-Wenv, and MAP lipoarabinomannan (LAM) demonstrated the strongest effect on anti-LAM Abs (p = 0.018), a slight reduction of anti-IL-2 Abs, and small variations for anti-HERV-Wenv Abs. These results highlight the conclusion that the impact of therapy is more correlated with selected epitopes than with the therapeutic agent. Screening for anti-IL-2 and anti-HERV-Wenv Abs has a potential as additional future practice to distinguish between symptomatically similar MS and NMOSD.

Evaluation of critical aspects in clinical and forensic management of sexual violence: A multicentre Ge.F.I. project.

Violence against women is a violation of human rights, crossing all cultures, classes, levels of education, earnings, ethnic and age groups. We conducted a retrospective study to review forensic records of sexual assault examinations carried out in different Italian health facilities and to correlate these findings with the results of the forensic DNA analyses. The goal was to determine which factors could have affected the obtained results, to identify the fundamental aspects to search for while examining a sexual assault victim in order to gather useful evidence to identify the offender and reconstruct the dynamics of the fact. We analysed 102 cases that occurred between 2006 and 2017, coming from ten participating laboratories. Despite a relatively limited number of cases, this study shows that the ability to ascertain the presence of male biological material in the samples collected is not a problem for forensic laboratories and seems to be influenced by other factors, such as how much time elapsed between the event and the sampling, the availability of the aggressor's biological material on the victim and the identification of biological fluids/stains. Therefore, the need for health structures to adopt specific protocols has been highlighted. It is necessary for health structures to define specific pathways and adopt homogeneous procedures or operational protocols, and it is essential to provide adequate training for health personnel. The results of the study could be useful in drafting and revising protocols/guidelines implemented in Italian hospital. Issues related to the limited number of analyses requested by Italian Authorities are also discussed.

Antibody response to homologous epitopes of Epstein-Barr virus, Mycobacterium avium subsp. paratuberculosis and IRF5 in patients with different connective tissue diseases and in mouse model of antigen-induced arthritis.

BACKGROUND: Improved knowledge of different biomarkers is crucial for early diagnosis of rheumatic diseases and to provide important insights for clinical management. In this study, we evaluated the seroreactivity of patients with different connective tissue diseases (CTDs) (rheumatoid arthritis, RA; systemic lupus erythematosus, SLE; systemic sclerosis, SSc; and Sjogren's syndrome, SSj) to interferon regulatory factor 5 (IRF5) peptide and homologs derived from Epstein-Barr virus (EBV) and Mycobacterium avium subsp. paratuberculosis (MAP). Antigen-induced arthritis (AIA) experiments have been performed in control and IRF5 conditional knockout mice to reinforce the hypothesis that antibodies generated against the three homologous peptides are cross-reactive. METHODS: Reactivity against wild-type (wt) and citrullinated (cit) IRF5 (IRF5424-434), MAP (MAP_402718-32) and EBV (BOLF1305-320) peptides were tested by indirect ELISA in sera from 100 RA patients, 54 patients with other CTDs (14 SLE, 28 SSc and 12 SSj) and 100 healthy subjects (HCs). Antibody responses to the same wt peptides have been tested in AIA mouse sera after immunization with complete Freud's adjuvant (CFA) and methylated bovine serum albumin (mBSA) to induce arthritis in the knee joint. RESULTS: BOLF1, MAP_4027 and IRF5 peptides triggered different antibody responses in CTD diseases with a stronger reactivity in RA (p=0.0001). Similar trends were observed in AIA mice with significantly higher reactivity after 7 days from induction of arthritis. We also found statistically significant differences in antibody responses between SSc and HCs for BOLF1 (p=0.003), MAP_4027 (p=0.0076) and IRF5 (p=0.0042). Peripheral reactivity to cit peptides was lower compared to their wt counterparts, except for cit-MAP_402718-32, which induced stronger responses in RA than wt-MAP_402718-32 (46% vs. 26%, p=0.0170). Conclusion(s): Our results show differential antibody responses to BOLF1, MAP_4027 and IRF5 peptides among CTDs, highlighting their potential as diagnostic biomarkers in these diseases. Experiments performed in IRF5 conditional knockout mice support the hypothesis of cross-reactivity between the investigated homologous antigens.

Antibody response against HERV-W in patients with MOG-IgG associated disorders, multiple sclerosis and NMOSD.

Increased expression of the retroviruses of HERV-W family has been linked to multiple sclerosis (MS) pathophysiology; nothing is known at the moment about MOG-IgG associated disorders. We compared antibody response against HERV-W peptides among patients with MOG-IgG associated disorders, multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD). A total of 102 serum samples were retrospectively analyzed. Antibody reactivity against HERV-W env peptides was similar in MOG-IgG associated disorders and MS, but different from AQP4-IgG positive NMOSD. Our findings expand the diagnostic role of HERV-W antibodies to the spectrum of demyelinating disorders associated with MOG-IgG.

[Quality evaluation of informed consent forms: a pilot study]. / La valutazione qualitativa del consenso informato: uno studio pilota.

Informed consent forms must be designed to meet specific requirements but evaluating the structure and content requirements of consent forms from a qualitative point of view is not a simple task. An evaluation tool was therefore developed in the context of a pilot study to evaluate the current quality of informed consent forms at both medical and surgical departments of the San Giovanni Battista Hospital in Turin (Italy). A random sample of 288 medical records of patients hospitalized during 2007-2008 was selected. These were evaluated to determine the presence of a properly executed informed consent form or of a justification for its absence. Each consent form was evaluated based on the presence of a list of requirements. Statistical analysis was conducted by first taking into account all departments and then stratifying by medical and surgical departments. The evaluation tool was found to useful in evaluating, in a standardized and repeatable manner, the adequacy and completeness of informed consent forms in different hospital departments.