Respects of human rights and perception of quality of care, the users' point of view comparing mental health and other health facilities in a region of Italy.

This work is part of a research project that aims to measure organisational well-being, human rights respect and quality of care in mental health services in Sardinia, Italy, country that has replaced long-stay psychiatric hospitals with community mental health services. Previous contributions have seen Italian health professionals and users as the most satisfied and optimistic about the quality of the mental health care provided and the respect they offer for service users' rights. Our aim is to confirm these findings by comparing experiences of users of mental health services with those of other care services in the same region. Our findings indicate that mental health services users show higher level of satisfaction for care and higher perception of users' human rights respect compared to non-mental health facilities users. They also have greater satisfaction with organisational aspects of services and they are more convinced that the health professionals rights are respected. In contrast, they are less satisfied with the resources available for care centres than other users and require more professional psychosocial support. We want to allow future comparisons to other regions on quality assessment through the perception of users and worker on respect for standards and human rights.

Ethical perspectives in communication in cancer care: An interpretative phenomenological study.

BACKGROUND: In cancer care, many clinical contexts still lack a good-quality patient-health professional communication about diagnosis and prognosis. Information transmission enables patients to make informed choices about their own healthcare. Nevertheless, disclosure is still an ethically challenging clinical problem in cancer care. High-quality care can be achieved by understanding the perspectives of others. The perspective of patients, their caregivers, physicians and nurses have seldom been simultaneously studied. OBJECTIVE: To investigate the phenomenon of diagnosis and prognosis-related communication as experienced by patients, their caregivers, and both their attending nurses and physicians, to enlighten meanings attached to communication by the four parties. METHODS: A qualitative study using interpretative phenomenological analysis was performed. PARTICIPANTS AND RESEARCH CONTEXT: Purposive sampling of six patients, six caregivers, seven nurses and five physicians was performed in two oncological hospitals in Italy. ETHICAL CONSIDERATIONS: Local Ethics Committee approved the study. It was guided by the ethical principles of voluntary enrolment, anonymity, privacy and confidentiality. RESULTS: Three main themes were identified: (a) the infinite range of possibilities in knowing and willing to know, (b) communication with the patient as a conflicting situation and (c) the bind of implicit and explicit meaning of communication. CONCLUSION: The interplay of meanings attached by patients, their caregivers, and their attending oncologist and nurse to communication about diagnosis and prognosis revealed complexities and ambiguities not yet settled. Physicians still need to solve the ethical tensions in their caring relationship with patients to really allow them 'to choose with dignity and being aware of it'. Nurses need to develop awareness about their role in diagnosis and prognosis-related communication. This cognizance is essential not just to assure consistency of communication within the multi-disciplinary team but mostly because it allows and enables the moral agent to take its own responsibilities and be accountable for them.

The role of collective affective commitment in the relationship between work-family conflict and emotional exhaustion among nurses: a multilevel modeling approach.

BACKGROUND: Work-family conflict (WFC) is a crucial problem in nursing because of the demanding conditions of the job, such as strenuous shifts, physical and emotional workload, and intense patient involvement. Using a multilevel approach, this study investigated the moderating role of collective affective commitment as a protective resource in the relationship between WFC and emotional exhaustion. METHODS: The sample included 647 nurses from 66 working units in 4 Italian hospitals. A self-administrated questionnaire was administered to nurses. To analyze data, hierarchical linear modeling was used to examine cross-level relationships between variables. RESULTS: The results indicated that emotional exhaustion increased with augmenting of WFC and that this relationship was stronger when collective affective commitment was low and weaker when it was high. CONCLUSIONS: The study thus suggests that collective affective commitment may be considered a protective resource for nurses. Moreover, the results show that high work-family conflict should not represent a serious problem when nurses have high affective commitment. Interventions at both individual and group level are discussed in order to mitigate WFC, promoting collective affective commitment and thus reducing emotional exhaustion.

Providing Personal Care to Patients: the Role of Nursing Students' Emotional Labor.

Background Providing personal care may be a source of emotional difficulties and negative feelings for students interacting with patients during their first clinical placement. This study was done to describe the role of emotional strategies for first year nursing students providing personal care to patients and the relationship of these strategies to students' emotional exhaustion, self-efficacy, and turnover intention. Method A self-reported questionnaire was administrated to a convenience sample of 226 first-year undergraduate nursing students attending their first clinical placement in one Italian University hospital. Results Results suggested a positive link between students' cognitive re-evaluation of their experiences and their self-perceived self-efficacy. Attentional deployment was the strongest antecedent of emotional exhaustion. Emotional dissonance was the primary contributor to students' turnover intention. Emotional exhaustion mediated the relationship between emotional dissonance and turnover intention. Conclusion This research suggested that there are emotional coping strategies useful for protecting student nurses from emotional exhaustion and turnover intention and that these strategies are positively related to students' self-perceived self-efficacy in providing personal care.

The psychological impact of diagnosis of sinonasal, nasopharyngeal, and laryngeal cancers: a systematic review.

Objective: High risk of degraded quality of life and psychological distress is observed in patients diagnosed with sinonasal, nasopharyngeal, and laryngeal cancers, which could be caused by exposure to carcinogens in workplaces. This review aimed to investigate the psychological impact of diagnosis associated with the possible occupational etiology of such neoplasms and to explore the instruments that evaluate the quality of life (QoL), anxiety, and depression in these patients. Methods: Studies were considered for the review only if they described aspects of the psychological impact of the diagnosis of sinonasal, nasopharyngeal, and laryngeal cancers and reported results distinguished by the tumor site. The psychological impact was assessed in terms of health-related QoL, anxiety, and depression using reliable psychometric questionnaires administered at the time of diagnosis and 1 year later. Results: In more than 5,900 records identified, 442 studies fulfilled the eligibility criteria and 436 were excluded after full-text screening, resulting in six studies to be finally included in the review. The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30), EORTC QLQ-H&N35, and Functional Assessment of Cancer Therapy (FACT) were used to evaluate the QoL, whereas the Hospital Anxiety and Depression Scale (HADS) and Center for Epidemiologic Studies Depression Scale (CES-D) questionnaires were employed to assess anxiety and depression. QoL scores were similar to those of the general population at the time of diagnosis and remained unchanged or slightly improved at 1 year since diagnosis. In contrast, a higher prevalence of anxiety and depression was observed compared with the general population, although the results were inconsistent across the very few studies identified. No study investigating the association between the potential occupational etiology and QoL or distress was found. Conclusion: Exploring the existing scientific literature on emotional distress in sinonasal, nasopharyngeal, and laryngeal cancer patients was prompted by concerns over the disfiguring nature of treatment and the additional emotional burden resulting from their occupational etiology. Unfortunately, neither a crucial element nor other risk factors (lifestyle, smoking, drinking, etc.) were examined in any study. Patients' employment history should be considered in order to assess the possible impact of believing they are affected by an occupational exposure disease in the evaluation of their psychological distress. This history would support evidence-based recommendations about dedicated psychological interventions.

Effect of a Low-Moderate Exercise Program on Dysmetabolism in Older Adults: Results of a Randomized Controlled Trial.

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group (p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.

The perception of professionals and users of the quality of care and respect for human rights in four outpatient care facilities of an Italian hospital during the Covid-19 pandemic.

Background: During the Covid-19 pandemic, delays in providing medical services, dissatisfaction, criticism toward health workers (HW) and the risk of burnout of HW in Italy have been documented. No studies have contrasted the point of view of HW and users on the quality of care and respect for human rights in health facilities. Objective: To compare the perception of users of their satisfaction with the care provided with the perception of HW of their satisfaction with work as well as the perception of the respect of HW "s and users" human rights. Methods: The "Well-Being at work and respect for human rights questionnaire" (WWRR) was administered on a sample of users (142) and HW (154) in four outpatient health care facilities of a hospital in Sardinia, Italy. Results: Users showed higher scores than HW on their satisfaction with the care received (p < 0.0001), the perception of respect for their human rights (p < 0.0001), and availability of resources for care (p < 0.0001). The HW scores were higher than 50% of the maximum in all items, but a relatively low score was reported on the HW's satisfaction of the resources and the respect for their rights. Conclusion: The satisfaction for care and respect for human rights in the outpatient health services was higher than expected. The relatively low score by the HWs in relation to the satisfaction with the resources and perception of respect for their human rights could be a wake-up call. The study does not involve emergency rooms, wards, or Covid units.

Why Was the Perception of Human Rights Respect and Care Satisfaction So High in Users of Italian Mental Health Services during the COVID-19 Pandemic?

The aim of this study was to compare users' and mental health workers' (MHW) perception of respect of human rights and job/care satisfaction in mental health services in Italy during the COVID-19 pandemic. A sample of users and MHW of Sardinia, Italy, fulfilled the "Well-Being at work and respect for human rights questionnaire" (WWRR). The study included 240 MHW and 200 users. Users showed a higher level of satisfaction of care than MHW of work, and a higher perception of the satisfaction of users and human rights respected for health workers. Both user and MHW responses were about 85% of the maximum score, except for satisfaction with resources. Responses were higher for users, but users and MHW both showed high levels of satisfaction. In previous surveys, MHW of Sardinia showed higher scores in all items of WWRR, except for satisfaction with resources, compared with workers from other health sectors of the same region, and with MHW from other countries. The low score for satisfaction with resources (in users and staff) is consistent with a progressive impoverishment of resources for mental health care in Italy. The study, although confirming the validity of the Italian model, fully oriented towards community, sets off an alarm bell on the risks resulting from the decrease in resources.

[Value of the microarray for the study of Laboratory Animal Allergy (LAA)]. / II microarray proteico per lo studio dell'allergia da animali da laboratorio (LAA): principi e prospettive.

Since 1989, the National Institute for Occupational Safety and Health (NIOSH) considers the Laboratory Animal Allergy - LAA a risk for workers and in 1998 the LAA has been recognized as occupational risk in the USA. Rat and mouse are the most source of allergens, not so much for the higher power of allergy respect to the other animals, but because represent the more utilized species in the research. Most of the allergens are members of the lipocalin superfamily, small extracellular proteins represented by at least 50 proteins that mainly bind or carry small hydrophobic molecules. The recent and innovative molecular techniques, as the microarray, have allow the characterization of numerous allergens. The protein microarray gives the possibility to study of IgE profile for each individual, simultaneos analysis of a wide number of parameters concerning the allergy, giving new diagnostic and therapeutic opportunities for the allergies. In the study of occupational allergy--as LAA--the protein microarray could improve: the identification and characterization of new allergens; the individuation of susceptible workers; the study of immunological responses in exposed workers; the strategies of prevention and protection; the environmental and housing conditions. The participation, formation and information of the workers could improve the behavioural and occupational practices, the use of personal and collective protective devices in order to reduce the exposure to LAA in occupational context.

Experiencing communication related to knowing the cancer diagnosis and prognosis: A multi-perspective interpretative phenomenological study.

PURPOSE: To understand the phenomenon of communication related to knowing the diagnosis and prognosis, by exploring the perspectives of patients with advanced cancer and those of their caregivers, physicians and nurses. METHODS: Drawing upon a multi-perspective design, a total of 27 semi-structured interviews involving four different groups of stakeholders (7 patients, 7 caregivers, 6 physicians, and 7 nurses) -who were linked by a carer-cared relationship-were conducted in two Oncology Departments of two Italian hospitals. Interpretative Phenomenological Analysis was used to interpret the participants' narratives. RESULTS: Two overarching themes were identified: The first theme "the «what is it?¼ and the «what will happen to me?¼" illustrates the two different paths of communication of diagnosis and prognosis. The second theme "Matching and mismatching in identifying the others as speakers" shows that not each of the four parties recognizes the others as reciprocal speakers on topics related to diagnosis and prognosis, although all of them display reciprocal communication interactions. CONCLUSIONS: Communication related to diagnosis and prognosis is often handled by health professionals without a comprehensive and integrated understanding of the communication approach. There is a correspondence between the nurses' perception of their extraneousness to the diagnosis and the prognosis related communication, and the descriptions and perceptions of the nurse's role reported by the other participants. Understanding how the different groups of stakeholders reciprocally interact and influence each other, can help to identify potential positive resources and detect hindrance in the implementation of an effective patient-centered approach, while avoiding silo cultures.

Emerging zoonotic viral infections of occupational health importance.

Emerging viral infections represent a public health risk pointed out by the spreading of pathogens with potential zoonotic risk. Moreover, the risk of zoonosis has probably been underestimated in occupational settings. A literature review between 2007 and 2018 was performed to identify evidences concerning the epidemiological associations between some emerging viruses and occupational diseases. Observational studies and case-reports were selected and analyzed. West Nile Virus (WNV) disease, Crimean-Congo Hemorrhagic Fever (CCHF) disease and Hepatitis E virus (HEV) infection were included in the review for their potential zoonotic transmission. The most important risk factor for acquiring WNV infection and CCHF infection is the exposure to infected mosquitoes and ticks, respectively; therefore, outdoor workers are at risk of infection. HEV is responsible for epidemics and endemics of acute hepatitis in humans, that can become infected through waterborne, foodborne and zoonotic transmission routes. A total of 10, 34 and 45 eligible studies for WNV, CCHF virus (CCFHV) and HEV, respectively, were analyzed by year, country, study design, risk group and outcomes. The occupational risk groups mainly included farm and agricultural workers, veterinarians, slaughterers, animal handlers, healthcare workers and soldiers. These findings support the need to develop effective interventions to prevent transmission of emerging viruses.

Cultural adaptation and psychometric validation of the Caring Efficacy scale in a sample of Italian nurses.

Caring is the essence of nursing practice. Caring Efficacy scale was developed with the purpose of measuring nurses' perceived self-efficacy in orienting and maintaining caring relationships with patients. Since any instruments measuring caring self-efficacy have not been developed in Italy, the study aimed at culturally adapting and validating Caring Efficacy scale in a sample of Italian nurses. A total of 300 registered nurses were asked to fill a self-reported questionnaire; translation-back-translation procedure was carried out to maintain semantic, idiomatic and conceptual equivalence of the original scale. Then, factor analysis was performed in order to test appropriateness of the factor structure. Convergent and discriminant validity was also tested. A two-factor structure with 17 items was found. Results show that Cronbach's Alpha value was 0.84 for Confidence to Care, and 0.75 for Doubts and Concerns. Correlation analysis for convergent and discriminant validity showed that Confidence to Care was positively correlated with sense of coherence and no significant correlation with Doubts and Concerns was found. Caring efficacy scale can be used by nurse managers as a way of assessing nurses' self-efficacy and their caring orientation, thus improving quality of patient care.

Caring efficacy: nurses' perceptions and relationships with work-related factors.

BACKGROUND AND AIM OF THE WORK: Caring nursing practice is central aspect of quality of services. It is important to assess nurses' caring experience in terms of perceived caring efficacy to make them aware of their outcomes and improve their strategies. The aims of the study was to analyze: (1) the caring efficacy level, (2) differences between the caring efficacy levels concerning  positive and negative work attitudes, (3) individual and organizational predictors of perceived caring efficacy. METHODS: 200 nurses were recruited from a University Hospital in Southern Italy. A self-reported questionnaire was administered. T-test was performed to analyze differences between caring efficacy levels concerning outcomes variables. Regression analysis was carried out to examine how some work factors were related to perceived caring efficacy. RESULTS: Participants referred high confidence to care (CC) for 55%, and low doubts and concerns (DC) for 72.9%. Nurses who had low DC had lower emotional exhaustion than nurses with moderate DC. Nurses with low DC had higher job satisfaction than nurses with high DC. Regarding CC levels, there were no differences between mean values for both attitudes at work. The emotional dissonance significantly predicted DC and CC. The supervisor support had a negative link with emotional dissonance, which in turn was negatively related to CC. CONCLUSIONS: Education and training should be addressed to reduce doubts and concerns to care and improve the ability to manage emotions. A work environment that value caring and give support in managing emotions can reduce emotional dissonance and improve caring self-efficacy.

Turner syndrome mosaicism: an unusual case with a de novo large dicentric marker chromosome: mos 45,X/46,X, ter rea(X;X)(p22.3;p22.3).

X/X translocations are quite rare in humans. The effect of this anomaly on the phenotype is variable and depends on the amount of deleted material and whether the chromosomes are joined by their long or short arms. We report an unusual case of Turner syndrome mosaicism in a 16-year-old girl, who was referred to our Institute for primary amenorrhoea associated with short stature. Endocrine evaluation revealed hypergonadotropic hypogonadism, which required a study of the karyotype. Cytogenetic analysis, performed on peripheral blood leucocytes, showed a mos 45,X/46,X,ter rea (X;X)(p22.3;p22.3) de novo karyotype. The prevalent cell line was 45,X (90% cells). A second cell line (10% cells) showed a very large marker chromosome, similar to a large metacentric chromosome. FISH (fluorescent in situ hybridisation) and molecular analysis revealed that the marker chromosome was dicentric and totally derived from the paternal X chromosome.

Biological occupational allergy: Protein microarray for the study of laboratory animal allergy (LAA).

BACKGROUND: Laboratory Animal Allergy (LAA) has been considered a risk for the workers since 1989 by the NIOSH. About one third of the Laboratory Animal Workers (LAWs) can manifest symptoms to LAA as asthma, rhinitis, conjunctivitis and cutaneous reactions. The prevalence of LAA-induced clinical symptoms has been estimated with a great variability (4-44%) also due to the different methodologies applied. OBJECTIVE: Evaluate the prevalence of IgE positivity to mouse and rat allergens in LAWs and assess which factors are predisposing to sensitization among subjects exposed to laboratory animals in the workplace. METHODS: One hundred LAWs were invited to fill out a questionnaire regarding current allergic symptoms, atopic history, home environment, previous and current occupational history. IgE reactivity versus specific allergens was evaluated with ImmunoCAP ISAC. RESULTS: Out of one hundred LAWs, 18% had a serum susceptibility to mouse and/or rat allergens and 42% reported to have occupational allergy symptoms. Combining the results acquired by ImmunoCAP ISAC and questionnaire, 17% of LAWs have been defined as LAWs-LAA positive since they present a positive IgE response and allergy symptoms, 1% LAWs-LAA sensitized, 25% LAWs-LAA symptomatic and 57% LAWs-LAA negative. Presence of previous allergy symptoms in work and life environment were significantly related to LAWs-LAA positive/sensitized. CONCLUSIONS: The study aimed to define the immunological profile of LAWs using the proteomic array as an innovative approach in the study of environmental and occupational exposure to allergens. We suggested a definition of LAWs-LAA considering serum IgE response and presence of allergy symptoms. The proposed approach has the advantage to provide a standard methodology for evaluating the specific IgE responsiveness to animal allergens in specific workplace also considering the immunological profile of workers referred to exposure in life and occupational environment.

Lack of respect, role uncertainty and satisfaction with clinical practice among nursing students: the moderating role of supportive staff.

BACKGROUND AND AIMS: Clinical learning placements provide a real-world context where nursing students can acquire clinical skills and the attitudes that are the hallmark of the nursing profession. Nonetheless, nursing students often report dissatisfaction with their clinical placements. The aim of this study was to test a model of the relationship between student's perceived respect, role uncertainty, staff support, and satisfaction with clinical practice. METHOD: A cross-sectional, descriptive survey was completed by 278 second- and third-year undergraduate nursing students. Specifically, we tested the moderating role of supportive staff and the mediating role of role uncertainty. RESULTS: We found that lack of respect was positively related to role uncertainty, and this relationship was moderated by supportive staff, especially at lower levels. Also, role uncertainty was a mediator of the relationship between lack of respect and internship satisfaction; lack of respect increased role uncertainty, which in turn was related to minor satisfaction with clinical practice. CONCLUSION: This study explored the experience of nursing students during their clinical learning placements. Unhealthy placement environments, characterized by lack of respect, trust, and support increase nursing students' psychosocial risks, thus reducing their satisfaction with their clinical placements. Due to the current global nursing shortage, our results may have important implications for graduate recruitment, retention of young nurses, and professional progression.

Climate change, vector-borne diseases and working population.

INTRODUCTION: Risks associated with climate change are increasing worldwide and the global effects include altered weather and precipitation patterns, rising temperatures and others; human health can be affected directly and indirectly. This paper is an overview of literature regarding climate changes, their interaction with vector-borne diseases and impact on working population. MATERIALS AND METHODS: Articles regarding climate changes as drivers of vector-borne diseases and evidences of occupational cases have been picked up by public databank. Technical documents were also included in the study. RESULTS: Evidences regarding the impact of climate changes on vector-borne diseases in Europe, provided by the analysis of the literature, are presented. DISCUSSION: Climate-sensitive vector-borne diseases are likely to be emerging due to climate modifications, with impacts on public and occupational health. However, other environmental and anthropogenic drivers such as increasing travelling and trade, deforestation and reforestation, altered land use and urbanization can influence their spread. Further studies are necessary to better understand the phenomenon and implementation of adaptation strategies to protect human health should be accelerated and strengthened.

Browsing isolated population data.

BACKGROUND: In our studies of genetically isolated populations in a remote mountain area in the center of Sardinia (Italy), we found that 80-85% of the inhabitants of each village belong to a single huge pedigree with families strictly connected to each other through hundreds of loops. Moreover, intermarriages between villages join pedigrees of different villages through links that make family trees even more complicated. Unfortunately, none of the commonly used pedigree drawing tools are able to draw the complete pedigree, whereas it is commonly accepted that the visual representation of families is very important as it helps researchers in identifying clusters of inherited traits and genotypes. We had a representation issue that compels researchers to work with subsets extracted from the overall genealogy, causing a serious loss of information on familiar relationships. To visually explore such complex pedigrees, we developed PedNavigator, a browser for genealogical databases properly suited for genetic studies. RESULTS: The PedNavigator is useful for genealogical research due to its capacity to represent family relations between persons and to make a visual verification of the links during family history reconstruction. As for genetic studies, it is helpful to follow propagation of a specific set of genetic markers (haplotype), or to select people for linkage analysis, showing relations between various branch of a family tree of affected subjects. AVAILABILITY: PedNavigator is an application integrated into a Framework designed to handle data for human genetic studies based on the Oracle platform. To allow the use of PedNavigator also to people not owning the same required informatics infrastructure or systems, we developed PedNavigator Lite with mainly the same features of the integrated one, based on MySQL database server. This version is free for academic users, and it is available for download from our site http://www.shardna.com.

Antigenic peptide molecular recognition by the DRB1-DQB1 haplotype modulates multiple sclerosis susceptibility.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that has a notably high incidence in Sardinia. Our study focuses on two HLA class II haplotypes associated with the disease in Sardinia, the rare predisposing DRB1*15:01-DQB1*06:02 and the widespread protective DRB1*16:01-DQB1*05:02. This framework enabled the highlighting of HLA binding pocket specificity and peptide recognition mechanisms by employing molecular dynamics simulations of the whole DRB1-DQB1 haplotype interacting with MBP- and EBV-derived peptides. We analyzed peptide-protein interaction networks and temporal evolution of the original complexes and after key amino acid mutations. The mutation G86V of the protective DRB1 allele exerted its effect mainly in the presence of the EBV viral peptide, with local and long range outcomes. However, the V38A mutation of the protective DQB1 showed a long range effect only in the case of the MBP myelin peptide. Our findings also demonstrate a DRB1/DQB1 complementary molecular recognition of peptides. This mechanism could provide a robust synergistic action and a differential role of DRB1 and DQB1 in tissues and in the time-steps towards autoimmunity. In addition, we demonstrate that negatively charged residues in pockets 4 and 9 play a role in MS susceptibility. Our findings are supported by recent experiments using a closely related MS animal model. Overall, our analysis confirms the role of the DRB1-DQB1 haplotype in conferring disease predisposition and could provide a valuable aid in designing optimal therapeutic peptides for MS therapy.