Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD

Functional outcome 5 years after non-operative treatment of type A spinal fractures

This study was conducted to study the functional outcome after non-operative treatment of type A thoracolumbar spinal fractures without neurological deficit. Functional outcome was determined following the International Classification of Functioning, Disability and Health, measuring restrictions in body function and structure, restrictions in activities, and restrictions in participation/quality of life. All patients were treated non-operatively for a type A thoracolumbar (Th11-L4) spinal fracture at the University Hospital Groningen, The Netherlands. Thirty-three of the eighty-one selected patients agreed to participate in the study (response-rate 41%). Respondents were older than non-respondents (mean 50.5 years vs. 39.2 years), but did not differ from each other concerning injury-related variables. Patients with a neurological deficit were excluded. Treatment consisted either of mobilisation without brace, or of bedrest followed by wearing a brace. Restrictions in body function and structure were measured by physical tests (dynamic lifting test and bicycle ergometry test); restrictions in activities were measured by means of questionnaires, the Roland Morris Disability Questionnaire (RMDQ) and Visual Analogue Scale Spine Score (VAS). Restrictions in participation/quality of life were assessed with the Short Form 36 (SF-36) and by means of return to work status. Thirty-seven per cent of the patients were not able to perform the dynamic lifting test within normal range. In the ergometry test, 40.9% of the patients performed below the lowest normal value, 36.4% of the patients achieved a high VO2-max. Mean RMDQ-score was 5.2, the mean VAS-score was 79. No significant differences between patients and healthy subjects were found in SF-36 scores, neither were differences found between braced and unbraced patients in any of the outcome measures. Concerning the return to work status, 10% of the subjects had stopped working and received social security benefits, 24% had arranged changes in their work and 14% had changed their job. We conclude that patients do reasonably well 5 years after non-operative treatment of a thoracolumbar fracture, although outcome is diverse in the different categories and physical functioning seems restricted in a considerable number of patients.</p

Narratives of therapeutic art-making in the context of marital breakdown: Older women reflect on a significant mid-life experience

This paper explores the narratives of three women aged 65-72 years. They reflected on an episode of therapeutic art-making in midlife, which addressed depression associated with marital crisis and breakdown. The narrative analysis focused upon on the ways in which participants narrated the events leading up to their participation in therapeutic art-making; the aspects of therapeutic art-making that continued to be given significance; the characters given primacy in the stories they told about their journey through therapy and marital breakdown; meanings, symbolic and otherwise, that participants ascribed to their artwork made during this turning point in their lives; and aspects of the narratives that conveyed present-day identities and artistic endeavors. The narratives revealed the complexity of the journey through marital breakdown and depression into health, and showed that therapeutic art-making could best be understood, not as a stand-alone experience, but as given meaning within the context of wider personal and social resources. Participants looked back on therapeutic art-making that occurred two decades earlier and still described this as a significant turning point in their personal development. Art as an adjunct to counselling/therapy was not only symbolically self-expressive but provided opportunity for decision-making, agency and a reformulated self-image

Interaction between extracellular matrix molecules and microbial pathogens: evidence for the missing link in autoimmunity with rheumatoid arthritis as a disease model.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation followed by tissue rebuilding or fibrosis. A failure by the body to regulate inflammation effectively is one of the hallmarks of RA. The interaction between the external environment and the human host plays an important role in the development of autoimmunity. In RA, the observation of anti-cyclic citrullinated peptide antibodies (ACPA) to autoantigens is well recognized. Citrullination is a post-translational modification mediated by peptidyl arginine deiminases, which exist in both mammalian and bacterial forms. Previous studies have shown how proteins expressed in the human extracellular matrix (ECM) acquire properties of damage-associated molecular patterns (DAMPs) in RA and include collagens, tenascin-C, and fibronectin (FN). ECM DAMPs can further potentiate tissue damage in RA. Recent work has shown that citrullination in RA occurs at mucosal sites, including the oral cavity and lung. Mucosal sites have been linked with bacterial infection, e.g., periodontal disease, where exogenous pathogens are implicated in the development of autoimmunity via an infectious trigger. Proteases produced at mucosal sites, both by bacteria and the human host, can induce the release of ECM DAMPs, thereby revealing neoepitopes which can be citrullinated and lead to an autoantibody response with further production of ACPA. In this perspectives article, the evidence for the interplay between the ECM and bacteria at human mucosal surfaces, which can become a focus for citrullination and the development of autoimmunity, is explored. Specific examples, with reference to collagen, fibrinogen, and FN, are discussed

Shifting Attention From Theory to Practice in Philosophy of Biology

Traditional approaches in philosophy of biology focus attention on biological concepts, explanations, and theories, on evidential support and inter-theoretical relations. Newer approaches shift attention from concepts to conceptual practices, from theories to practices of theorizing, and from theoretical reduction to reductive retooling. In this article, I describe the shift from theory-focused to practice-centered philosophy of science and explain how it is leading philosophers to abandon fundamentalist assumptions associated with traditional approaches in philosophy of science and to embrace scientific pluralism. This article comes in three parts, each illustrating the shift from theory-focused to practice-centered epistemology. The first illustration shows how shifting philosophical attention to conceptual practice reveals how molecular biologists succeed in identifying coherent causal strands within systems of bewildering complexity. The second illustration suggests that analyzing how a multiplicity of alternative models function in practice provides an illuminating approach for understanding the nature of theoretical knowledge in evolutionary biology. The third illustration demonstrates how framing reductionism in terms of the reductive retooling of practice offers an informative perspective for understanding why putting DNA at the center of biological research has been incredibly productive throughout much of biology. Each illustration begins by describing how traditional theory-focused philosophical approaches are laden with fundamentalist assumptions and then proceeds to show that shifting attention to practice undermines these assumptions and motivates a philosophy of scientific pluralism

Exploiting disorder for perfect focusing

We demonstrate experimentally that disordered scattering can be used to improve, rather than deteriorate, the focusing resolution of a lens. By using wavefront shaping to compensate for scattering, light was focused to a spot as small as one tenth of the diffraction limit of the lens. We show both experimentally and theoretically that it is the scattering medium, rather than the lens, that determines the width of the focus. Despite the disordered propagation of the light, the profile of the focus was always exactly equal to the theoretical best focus that we derived.Comment: 4 pages, 4 figure

Symbioses shape feeding niches and diversification across insects.

For over 300 million years, insects have relied on symbiotic microbes for nutrition and defence. However, it is unclear whether specific ecological conditions have repeatedly favoured the evolution of symbioses, and how this has influenced insect diversification. Here, using data on 1,850 microbe-insect symbioses across 402 insect families, we found that symbionts have allowed insects to specialize on a range of nutrient-imbalanced diets, including phloem, blood and wood. Across diets, the only limiting nutrient consistently associated with the evolution of obligate symbiosis was B vitamins. The shift to new diets, facilitated by symbionts, had mixed consequences for insect diversification. In some cases, such as herbivory, it resulted in spectacular species proliferation. In other niches, such as strict blood feeding, diversification has been severely constrained. Symbioses therefore appear to solve widespread nutrient deficiencies for insects, but the consequences for insect diversification depend on the feeding niche that is invaded