Self-reported psychological symptoms and severe stress events, but not patients' gender, affect illness representation and medical advice by lay-referral network advisors.

People who experience symptoms tend to discuss their ailments with other individuals who create their own illness representations, acting as intuitive physicians. We conducted two experimental studies to examine lay-referral network advisors' (i.e., acquaintances) representation of illness etiology and their recommendation to undergo health screenings for a man or woman with physical (vs. both physical and psychological) symptoms and a severe stressful (vs. no stressful) period in life. The presence of psychological and physical symptoms (Studies 1 and 2) and severe stressful life events (Study 2) affects lay-referral network advisors' disease representation. These factors cause participants to attribute symptoms etiology to psychological rather than organic factors and recommend more psychological screenings rather than physical ones. The simultaneous presence of psychological and physical symptoms and severe stressful events increases the likelihood of attributing the illness etiology to psychological factors, which increases participants' willingness to recommend psychological screenings. Study variables were unaffected by patient gender. The main findings, limitations, and future directions are discussed.

Prospects for gene replacement therapies in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating and incurable neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. ALS causes death, usually within 2-5 years of diagnosis. Riluzole, the only drug currently approved in Europe for the treatment of this condition, offers only a modest benefit, increasing survival by 3 months on average. Recent advances in our understanding of causative or disease-modifying genetic variants and in the development of genetic therapy strategies present exciting new therapeutic opportunities for ALS. In addition, the approval of adeno-associated virus-mediated delivery of functional copies of the SMN1 gene to treat spinal muscular atrophy represents an important therapeutic milestone and demonstrates the potential of gene replacement therapies for motor neuron disorders. In this Review, we describe the current landscape of genetic therapies in ALS, highlighting achievements and critical challenges. In particular, we discuss opportunities for gene replacement therapy in subgroups of people with ALS, and we describe loss-of-function mutations that are known to contribute to the pathophysiology of ALS and could represent novel targets for gene replacement therapies.

"You are stealing our present": Younger people's ageism towards older people predicts attitude towards age-based COVID-19 restriction measures.

The COVID-19 pandemic emerged to be a fertile ground for age-based prejudice and discrimination. In particular, a growing literature investigated ageism towards older people at the individual and the interpersonal level, providing evidence of its prevalence, antecedents and negative consequences. However, less much is known on the phenomenon at the intergroup level. To fill this gap, the present correlational research investigated the effects of younger people's endorsement of ageism towards older people on the attitude towards COVID-19 restriction measures primarily targeted to older (vs. younger) population. In the autumn of 2020, five hundred and eighty-two Italian participants (83.3% females; M age = 20.02, SD age = 2.83) completed an online questionnaire. Results revealed that the younger people's endorsement of ageism towards older people increased the attribution of culpability for the severity of COVID-19 restriction measures to older (vs. younger) people, which, in turn positively affected the attitudes towards older (vs. younger) people isolation and support for selective lockdown on older population only. The main contributions of the study, limitations, future research directions, and practice implications are discussed.

Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with amyotrophic lateral sclerosis. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for 5 days every 28 days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-regulatory T-cell-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient regulatory T-cell-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis.

The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS).

BACKGROUND: Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. MAIN BODY: The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. CONCLUSION: Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.

Legitimizing Intimate Partner Violence: Moral Evaluations, Attribution of Responsibility, and (Reduced) Helping Intentions.

This article examines the influence of moral evaluations and attribution of responsibility on individuals' willingness to provide help if witnessing an intimate partner violence (IPV) episode. A total of 121 undergraduates read a fictitious article from a newspaper, allegedly describing an IPV episode. According to the experimental condition, participants read that the victim had either admitted infidelity or denied it. After reading the newspaper article, participants evaluated the victim on several dimensions (i.e., morality, competence, and sociability), rated the extent to which they deemed her responsible for the violence (i.e., the internal attribution of what happened), and expressed their willingness to provide help and support to the victim herself. In the admission condition, the victim was evaluated as less moral and more responsible for the episode of IPV. These evaluations, in turn, lowered the willingness to provide help to the victim. This study confirmed the role of moral evaluations and internal attribution on bystanders' reaction, and we present practical implications for intervention in a field, IPV, in constant need of updated validated evidence for efficient prevention strategies.

"If I Am Straight You Are Askew": Labelling Heterosexuals as Straight Worsen Gay Men's Perception.

A robust stream of research has shown the detrimental influence of slurs and derogatory epithets on attitudes toward minority groups. Extending prior work, we explored the influence of positive labels ascribed to the majority group on the evaluation of the minority group. Specifically, three studies tested the possibility that the label "straight," generally linked with the concept of morality, would promote a negative evaluation of gay men. Study 1 exposed English speakers to an individual person described as straight (vs. heterosexual) while Study 2 exposed English speakers to a target person described as straight (vs. heterosexual vs. no label). Study 3 considered a non-English sample (i.e., Italian adults) and experimentally induced the association between the straight label and the concept of heterosexuality. In each study, participants were asked to express their attitudes toward a gay target after the manipulation. Results showed that heterosexual participants exposed to the label "straight" reported more negative attitudes toward gay men than heterosexual participants exposed to the label "heterosexual" (or when they were not exposed to any label). Critically, such an effect emerged only among highly religious participants. Implications for policies and prejudice reduction are discussed.

System justification moderates the relation between hostile (but not benevolent) sexism in the workplace and state anxiety: An experimental study.

In an experimental vignette study performed with 92 Portuguese women, we analyzed the relations between exposure to hostile sexism (HS) and benevolent sexism (BS) in a workplace context, system justification (SJ), and anxiety, measured after participants were exposed to an HS, a BS, or a neutral communication about the context of the industry they would have worked in, if selected. The results indicated that both HS and BS fostered participants' anxiety, and that SJ moderated the relation between HS and anxiety. Anxiety was highest among participants low in SJ. Main contributions of the study, limitations, and possible future research directions are discussed.

Differential toxicity of TAR DNA-binding protein 43 isoforms depends on their submitochondrial localization in neuronal cells.

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein and a major component of protein aggregates found in amyotrophic lateral sclerosis and several other neurodegenerative diseases. TDP-43 exists as a full-length protein and as two shorter forms of 25 and 35 kDa. Full-length mutant TDP-43s found in amyotrophic lateral sclerosis patients re-localize from the nucleus to the cytoplasm and in part to mitochondria, where they exert a toxic role associated with neurodegeneration. However, induction of mitochondrial damage by TDP-43 fragments is yet to be clarified. In this work, we show that the mitochondrial 35 kDa truncated form of TDP-43 is restricted to the intermembrane space, while the full-length forms also localize in the mitochondrial matrix in cultured neuronal NSC-34 cells. Interestingly, the full-length forms clearly affect mitochondrial metabolism and morphology, possibly via their ability to inhibit the expression of Complex I subunits encoded by the mitochondrial-transcribed mRNAs, while the 35 kDa form does not. In the light of the known differential contribution of the full-length and short isoforms to generate toxic aggregates, we propose that the presence of full-length TDP-43s in the matrix is a primary cause of mitochondrial damage. This in turn may cause oxidative stress inducing toxic oligomers formation, in which short TDP-43 forms play a major role.

Visits to figurative art museums may lower blood pressure and stress.

BACKGROUND: The research aimed to assess, through physiological measurements such as blood pressure and heart rate, whether exposure to art museums and to different art styles (figurative vs. modern art) was able to enhance visitors' well-being in terms of relaxing and stress reduction. METHOD: Participants (n = 77) were randomly assigned to one of three conditions, on the basis of the typology of the art style they were exposed to in the museum visit: (1) figurative art, (2) modern art and (3) museum office (as a control condition). Blood pressure and heart rate were measured before and after the visits. RESULTS: Diastolic values of the participants were quite stable, as expected in people who do not suffer hypertension; we therefore considered only variations in systolic blood pressure. The majority of the participants exposed to figurative art significantly decreased systolic blood pressure compared to those exposed to modern art and museum office. No differences were found in the heart rate before and after the visit for the three groups. CONCLUSION: Findings suggest that museum visits can have health benefits, and figurative art may decrease systolic blood pressure.

A Universal Mental Health Promotion Programme for Young People in Italy.

In Italy, the Mental Health Unit of the National Institute of Public Health has developed a school-based mental health programme based on a structured handbook. The aim of this programme is to promote self-efficacy, psychological well-being, and life satisfaction. In this study, we evaluated the effectiveness of this programme. We used data from 308 students who participated in a study in 9 Italian high schools during the 2011-2012 school year. In order to analyse the school intervention programme, we set up a pre-post test design study involving 18 classrooms (8 of which acting as a control). The schools were selected via a snowball technique, and then the classrooms that agreed to participate were randomly assigned to intervention and control groups. The programme was performed during regular school hours in one-hour a week sessions for a total of 20 hours of classroom time. Assessments before and 2 months after the programme were performed using Regulatory Emotional Self-Efficacy, Satisfaction With Life, and Ryff's Psychological Well-Being Scales. The results showed an improvement in self-efficacy in regulating negative affect, overall psychological well-being, and satisfaction with life. These results demonstrate that the programme produced significant positive effects on the mental health status of participating students.

Actions improving HPV vaccination uptake - Results from a national survey in Italy.

BACKGROUND: In Italy, HPV vaccination is offered to 11-year-old girls since 2007. In 2012 coverage was 69%. Strategies for offering and promoting HPV vaccination and coverage rates (26-85%) vary among Regions and Local Health Authorities (LHAs). We conducted a national study to identify strategies to improve HPV vaccination uptake. METHODS: In 2011-2012 we invited the 178 LHAs to fill a web-questionnaire, inquiring implementation of HPV vaccination campaigns (immunization practices, logistics of vaccine delivery, training, activities to promote vaccination, barriers, local context). We described type of offer and vaccination promotion in each LHA and studied the association of these factors with vaccination coverage rates. RESULTS: We analyzed 133 questionnaires. The communication tools more frequently used to promote vaccination were: brochures/leaflets (92% of LHAs), fliers/posters (72%). Television (24%) and radio (15%) were less used. Using ≥3 communication channels was associated to a coverage ≥70% (ORadj=5.9, 95%CI 2.0-17.4). The probability to reach a coverage ≥70% was higher if the invitation letter indicated a pre-assigned date for HPV vaccination (ORadj=7.0, 95%CI 1.2-39.8) and >1 recall for non-respondents was planned (ORadj=4.1, 95%CI 1.8-9.3). Immunization services and paediatricians were involved in informative and training activities in most LHAs (80-90%), instead general practitioners, women and family's healthcare services and public gynaecologists in 60-70%, cervical cancer screening services and private gynaecologists in 20-40%. The main factors that negatively affected vaccination uptake were: poor participation to training events of professional profiles different from personnel of immunization services (reported by 58% LHAs), their mistrust towards HPV vaccination (55%) and insufficient resources (56%). CONCLUSION: The synergy of multiple interventions is necessary for a successful vaccination programme. Practices such as pre-assigning vaccination date and repeatedly recalling non-respondents could improve vaccination uptake. Efforts are required to strengthen the training of different professional profiles and services and encourage their collaboration. Economical resources are needed to promote vaccination.

Exploring reasons for non-vaccination against human papillomavirus in Italy.

BACKGROUND: In Italy, free-of-charge HPV vaccination is offered to 11-year-old girls since 2007. The National Immunization Plan established the target coverage at a minimum of 70%; it should increase to 95% within 3-year time frame. In 2012, four year after the introduction of HPV vaccination, coverage was stable at 69%. We conducted a national cross-sectional study to explore barriers to vaccination in Italy. METHODS: Vaccination services selected, through the immunization registries, a sample of unvaccinated girls born in 1997 or 1998 and posted to their families a 23-items questionnaire inquiring barriers to vaccination, HPV knowledge, source of information on HPV, perception of risk of contracting HPV, advice from consulted health professionals on HPV vaccination. RESULTS: We analysed 1,738 questionnaires. Main barriers were fear of adverse events (reported by 80% of families), lack of trust in a new vaccine (76%), discordant information received by health professionals (65%) and scarce information on HPV vaccination (54%). Overall, 54% of families replied correctly to more than half of 10 questions exploring knowledge on HPV vaccination. Families with a high knowledge score were more likely to live in Northern and Central Italy, be Italian, have a high educational level, include a mother who attended cervical screening regularly and consult more information sources. Although paediatricians/general practitioners and gynaecologists were considered the most trusted source of information by 79% and 61% of respondents, they were consulted only by 49% and 31%. Among parents who discussed vaccination with a physician, 28% received discordant advices and 31% received the recommendation of accepting vaccination. CONCLUSIONS: Fear of adverse events, discordance of information and advices from physicians, and scarce information were the more commonly reported barriers to HPV vaccination. Health professionals played a key role as information providers, thus they must be better trained to provide clear notions. Training needs to include the development of communication skills; transparent discussion about the pros and cons of vaccination may reduce fear of adverse events and increase trust in vaccination. The creation of a public health network around vaccination would allow sharing information and attitudes on vaccinations, so that homogeneous messages could reach the target population.