Most nuclear systemic autoantigens are extremely disordered proteins: implications for the etiology of systemic autoimmunity

Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies in normal individuals

The outbreak of SARS at Tan Tock Seng Hospital--relating epidemiology to control.

INTRODUCTION: The outbreak of severe acute respiratory syndrome (SARS) began after the index case was admitted on 1 March 2003. We profile the cases suspected to have acquired the infection in Tan Tock Seng Hospital (TTSH), focussing on major transmission foci, and also describe and discuss the impact of our outbreak control measures. MATERIALS AND METHODS: Using the World Health Organization (WHO) case definitions for probable SARS adapted to the local context, we studied all cases documented to have passed through TTSH less than 10 days prior to the onset of fever. Key data were collected in liaison with clinicians and through a team of onsite epidemiologists. RESULTS: There were 105 secondary cases in TTSH. Healthcare staff (57.1%) formed the majority, followed by visitors (30.5%) and inpatients (12.4%). The earliest case had onset of fever on 4 March 2003, and the last case, on 5 April 2003. Eighty-nine per cent had exposures to 7 wards which had cases of SARS that were not isolated on admission. In 3 of these wards, major outbreaks resulted, each with more than 20 secondary cases. Attack rates amongst ward-based staff ranged from 0% to 32.5%. Of 13 inpatients infected, only 4 (30.8%) had been in the same room or cubicle as the index case for the ward. CONCLUSIONS: The outbreak of SARS at TTSH showed the challenges of dealing with an emerging infectious disease with efficient nosocomial spread. Super-spreading events and initial delays in outbreak response led to widespread dissemination of the outbreak to multiple wards

Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study.

BackgroundOmega-3 fatty acids prevent cardiovascular disease (CVD) events in patients with myocardial infarction or heart failure. Benefits in patients without overt CVD have not been demonstrated, though most studies did not use treatment doses (3.36 g) of omega-3 fatty acids. Arterial stiffness measured by pulse wave velocity (PWV) predicts CVD events independent of standard risk factors. However, no therapy has been shown to reduce PWV in a blood pressure-independent manner. We assessed the effects of esterified omega-3 fatty acids on PWV and serum markers of inflammation among patients with hypertension.Design and methodsWe performed a prospective, randomized; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban, safety net hospital. Patients received 3.36 g of omega-3 fatty acids vs. matched placebo daily for 3-months. The principal outcome measure was change in brachial-ankle PWV. Serum inflammatory markers associated with CVD risk were also assessed.ResultsThe majority (71 %) were of Latino ethnicity. After 3-months, mean change in arterial PWV among omega-3 and placebo groups was -97 cm/s vs. -33 cm/s respectively (p = 0.36 for difference, after multivariate adjustment for baseline age, systolic blood pressure, and serum adiponectin). Non-significant reductions in lipoprotein-associated phospholipase A2 (LpPLA2) mass and high sensitivity C-reactive protein (hsCRP) relative to placebo were also observed (p = 0.08, and 0.21, respectively).ConclusionHigh-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension.Clinical trial registrationNCT00935766 , registered July 8 2009

Mycorrhizal Development and Phosphorus Concentration in selected Kenyan Sorghum Cultivars

This study was carried out on sorghum genotypes that exhibited significant difference in growth and production on P-deficient soils. The objective was to find out if the genotypes developed different levels of mycorrhizal associations and tissue phosphorus. Results showed that plants in unfertilized soils developed extensive mycorrhizae than those in fertilized soils, no significant differences was observed in the extent of mycorrhizal development among cultivars grown in P-fertilized soils. The cultivars in unfertilized soils responded differently to mycorrhizal colonization, those with high level of mycorrhizal development increased growth compared to those that had low levels of mycorrhizal development in the unfertilized soils. The cultivars also responded differently to phosphorus concentration in their tissues. Phosphorus fertilizer apparently increased number of leaves and sorghum plant height. There was no relationship between phosphorus concentration in soil and level of mycorrhizal development though fertilizer significantly suppressed the level of mycorrhizal development in the plant

Interdisciplinary Collaborative Practice in Early Childhood

Young children often present with challenging behaviors such as tantrums, aggression, and noncompliance. Rates of expulsion for behavior concerns in early childhood are alarming and can have long-term negative implications for children and their families (Early Childhood Learning and Knowledge Center, 2022). Implementation of a systematic multi-tiered system of supports framework can improve behavioral outcomes of young children. To effectively meet child and family needs within these frameworks, it is integral for members of the team to collaborate. Interdisciplinary teams within early childhood might include families, teachers, school psychologists, behavior analysts, speech language pathologists, physical therapists, occupational therapists and other related mental health and medical providers. The Interprofessional Education Collaborative outlined competencies for interdisciplinary collaborative practice that are organized within four domains: values and ethics, roles/responsibilities, interdisciplinary communication, and teams/teamwork. To facilitate interdisciplinary collaboration (IC) in practice, it is important to provide opportunities for collaboration across disciplines within coursework and field experiences. In this paper, we provide an example of an interdisciplinary training program to support behavioral and mental health needs of children. The training includes graduate students in applied behavior analysis, school psychology, and special education. Scholars participating in the program complete coursework for their specific programs in addition to joint coursework, seminars, and practicum activities in school settings. Throughout the program, scholars gain knowledge and skills in eight competencies identified for the program. Based on the literature and our training experience, we also outline insights and actions for training at the university-level and practitioner-level to implement interdisciplinary teaming

Assembling and Validating Data from Multiple Sources to Study Care for Veterans with Bladder Cancer

Despite the high prevalence of bladder cancer, research on optimal bladder cancer care is limited. One way to advance observational research on care is to use linked data from multiple sources. Such big data research can provide real-world details of care and outcomes across a large number of patients. We assembled and validated such data including (1) administrative data from the Department of Veterans Affairs (VA), (2) Medicare claims, (3) data abstracted by tumor registrars, (4) data abstracted via chart review from the national electronic health record, and (5) full text pathology reports

Impact Evaluation of the European Employment Strategy in Ireland. ESRI General Papers

Recent years have seen dramatic growth in employment following unprecedented economic growth and development during the 1990s. Total employment in Ireland grew by a remarkable 534,000, or by 46%, in the eight years from 1993 to 2001, and over 220,000 of this was achieved between 1998 and 2001. In very recent years, the rate of growth in employment fallen somewhat, from a peak of almost 7% in 1997-1998 to about 4% in 2000- 2001. The rapid growth in the economy and in employment after 1993 led to a steady decline in unemployment from 220,000 in 1993 to 127,000 in the 2nd quarter of 1998 and to 65,000 in the 2nd quarter of 2001. The unemployment rate thus fell from 15.7% of the labour force in 1993 to 7.8% in the 2nd quarter of 1998 and to 3.7% in the 2nd quarter of 2001. With the deterioration in the international economy, and the slowdown in the Irish growth rate in 2001, unemployment increased to just under 80,000, or 4.3% of the labour force, in the 3rd quarter of 2001

A tangled start:The link between childhood maltreatment, psychopathology, and relationships in adulthood

Background: Adults with a history of childhood maltreatment are more likely to experience distrust, feel distant from others, and develop an insecure attachment style which may also affect relationship quality. Furthermore, childhood maltreatment has been linked to several mental health problems; including, depression, anxiety, and alcohol dependance severity, that are also known to relationship quality. Objective: The current study was designed to investigate to what extent childhood maltreatment is associated with adult insecure attachment and intimate relationships and whether this association is mediated by psychopathology. Participants and Method: In a study comprised of 2035 adults aged 18-65, we investigated whether childhood maltreatment was associated with insecure adult attachment styles and the quality of intimate relationships and whether this was mediated by depression, anxiety, and alcohol dependence severity (based on repeated assessments of the Inventory of Depressive Symptomatology-Self Report, Beck Anxiety Index, and Alcohol Use Disorders Identification Test respectively). Results: The path model showed an acceptable fit, RMSEA = 0.05, and suggested full mediation of the association of childhood maltreatment with quality of intimate relationships by depression severity and a) anxious attachment (13 = -4.0 * 10-2; 95% CI = -5.5 * 10-2, -2.7 * 10-2) and b) avoidant attachment (13 = -7.2 * 10-2; 95% CI = -9.6 * 10-2, -4.9 * 10-2). Anxiety and alcohol dependence severity were not significant mediators. Conclusions: Childhood maltreatment is associated with a lower quality of intimate relationships, which is fully mediated by depression severity and insecure attachment styles.Prevention, Population and Disease management (PrePoD)Public Health and primary car