Search

The etiology of psychotic disorders is still unknown, but in a subgroup of patients symptoms might be caused by an autoimmune reaction. In this study, we tested patterns of autoimmune reactivity against potentially novel hippocampal antigens. Serum of a cohort of 621 individuals with psychotic disorders and 257 controls were first tested for reactivity on neuropil of rat brain sections. Brain reactive sera (67 diseased, 27 healthy) were further tested for antibody binding to glutamic acid decarboxylase (GAD) isotype 65 and 67 by cell-based assay (CBA). A sub-cohort of 199 individuals with psychotic disorders and 152 controls was tested for the prevalence of anti-nuclear antibodies (ANA) on HEp2-substrate as well as for reactivity to double-stranded DNA, ribosomal P (RPP), and cardiolipin (CL). Incubation of rat brain with serum resulted in unidentified hippocampal binding patterns in both diseased and control groups. Upon screening with GAD CBA, one of these patterns was identified as GAD65 in one individual with schizophrenia and also in one healthy individual. Two diseased and two healthy individuals had low antibody levels targeting GAD67 by CBA. Antibody reactivity on HEp-2-substrate was increased in patients with schizoaffective disorder, but only in 3 patients did antibody testing hint at a possible diagnosis of systemic lupus erythematosus. Although reactivity of serum to intracellular antigens might be increased in patients with psychotic disorder, no specific targets could be identified. GAD antibodies are very rare and do not seem increased in serum of patients with psychotic disorders. ispartof: Schizophrenia Research vol:228 pages:462-471 ispartof: location:Netherlands status: Published online

Funding: This work was funded by UK Research and Innovation (UKRI) (Coronavirus Disease [COVID-19] Rapid Response Initiative; MR/V028790/1 to C.D.L., D.A.D., and J.A.H.), LifeArc (through the University of Edinburgh STOPCOVID funding award, to K.D, D.A.D., C.D.L), The Chief Scientist Office (RARC-19 Funding Call, ‘Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis; COV/EDI/20/10’ to D.A.D, C.D.L, C.D.R, J.K.B and D.J.H), and Medical Research Scotland (CVG-1722- 2020 to DAD, CDL, CDR, JKB, and DJH). C.D.L is funded by a Wellcome Trust Clinical Career Development Fellowship (206566/Z/17/Z). J.K.B. and C.D.R. are supported by the Medical Research Council (grant MC_PC_19059) as part of the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC-4C). C.D.R. is supported by an Edinburgh Clinical Academic Track (ECAT)/Wellcome Trust PhD Training Fellowship for Clinicians award (214178/Z/18/Z). J.A.H. is supported by the U.S. Food and Drug Administration (contract 75F40120C00085, Characterization of severe coronavirus infection in humans and model systems for medical countermeasure development and evaluation’). G.C.O is funded by an NRS Clinician award. N.N.G. is funded by a Pathological Society Award. A.R.A. is supported by a Cancer Research UK Clinician Scientist Fellowship award (A24867). Immunopathology occurs in the lung and spleen in fatal COVID-19, involving monocytes/macrophages and plasma cells. Anti-inflammatory therapy reduces mortality but additional therapeutic targets are required. We aimed to gain mechanistic insight into COVID-19 immunopathology by targeted proteomic analysis of pulmonary and splenic tissues. Lung parenchymal and splenic tissue was obtained from 13 post-mortem examinations of patients with fatal COVID-19. Control tissue was obtained from cancer resection samples (lung) and deceased organ donors (spleen). Protein was extracted from tissue by phenol extraction. Olink® multiplex immunoassay panels were used for protein detection and quantification. Proteins with increased abundance in the lung included MCP-3, antiviral TRIM21 and pro-thrombotic TYMP. OSM and EN-RAGE/S100A12 abundance was correlated, and associated with inflammation severity. Unsupervised clustering identified ‘early viral’ and ‘late inflammatory’ clusters with distinct protein abundance profiles, and differences in illness duration prior to death and presence of viral RNA. In the spleen, lymphocyte chemotactic factors and CD8A were decreased in abundance, and pro-apoptotic factors were increased. B-cell receptor signalling pathway components and macrophage colony stimulating factor (CSF-1) were also increased. Additional evidence for a sub-set of host factors (including DDX58, OSM, TYMP, IL-18, MCP-3 and CSF-1) was provided by overlap between (i) differential abundance in spleen and lung tissue, (ii) meta-analysis of existing datasets, and (iii) plasma proteomic data. This proteomic analysis of lung parenchymal and splenic tissue from fatal COVID-19 provides mechanistic insight into tissue anti-viral responses, inflammation and disease stages, macrophage involvement, pulmonary thrombosis, splenic B-cell activation and lymphocyte depletion. Publisher PDF

Apolipoprotein ε4 (APOE)4 is a strong risk factor for the development of Alzheimer’s disease (AD) and aberrant sphingolipid levels have been implicated in AD. We tested the hypothesis that the APOE4 genotype affects brain sphingolipid levels in AD. Seven ceramides and sphingosine-1-phosphate (S1P) were quantified by LC-MSMS in hippocampus, cortex, cerebellum, and plasma of 5 months old human APOE3 and APOE4-targeted replacement mice with or without the familial AD (FAD) background of both sexes (145 animals). APOE4 mice had higher Cer(d18:1/24:0) levels in the cortex (1.7-fold, p = 0.002) than APOE3 mice. Mice with AD background showed higher levels of Cer(d18:1/24:1) in the cortex than mice without (1.4-fold, p = 0.003). S1P levels were higher in all three brain regions of older mice than of young mice (1.7-1.8-fold, all p ≤ 0.001). In female mice, S1P levels in hippocampus (r = −0.54 [−0.70, −0.35], p < 0.001) and in cortex correlated with those in plasma (r = −0.53 [−0.71, −0.32], p < 0.001). Ceramide levels were lower in the hippocampus (3.7–10.7-fold, all p < 0.001), but higher in the cortex (2.3–12.8-fold, p < 0.001) of female than male mice. In cerebellum and plasma, sex effects on individual ceramides depended on acyl chain length (9.5-fold lower to 11.5-fold higher, p ≤ 0.001). In conclusion, sex is a stronger determinant of brain ceramide levels in mice than APOE genotype, AD background, or age. Whether these differences impact AD neuropathology in men and women remains to be investigated.

Background: Tissue inflammation in fatal COVID-19 is concentrated in the lung and spleen. Anti-inflammatory therapy reduces mortality but knowledge on the host response at the level of inflamed tissues is incomplete. Methods: We performed targeted proteomic analysis of pulmonary and splenic tissues from 13 fatal cases of COVID-19 that underwent rapid autopsy, and compared to control tissues from cancer resection (lung) and deceased organ donors (spleen). Viral RNA presence was determined by multiplex PCR, and protein was isolated from tissue by phenol extraction. Targeted multiplex immunoassay panels were used for protein detection and quantification. Findings: Pulmonary proteins with increased abundance in COVID-19 included the monocyte/macrophage chemoattractant MCP-3, antiviral TRIM21 and pro-thrombotic TYMP. The lung injury markers OSM and EN-RAGE/S100A12 were highly correlated and associated with tissue inflammation severity. Unsupervised clustering of lung proteomes clearly defined two COVID-19 clusters; these differed by viral presence, tissue inflammation severity and illness duration and were annotated ‘early viral’ and ‘late inflammatory’ groups. In the spleen, lymphocyte chemotactic factors and CD8A were decreased in COVID-19, with pro-apoptotic factors, B-cell signalling components and macrophage colony stimulating factor (CSF-1) all increased. To contextualise our findings, we cross-referenced an existing meta-analysis of host factors in COVID-19 (MAIC). Overlap with a substantial sub-set of factors (including DDX58, OSM, TYMP, IL-18, MCP-3 and CSF-1) was found, with numerous additional proteins also identified by our study. Interpretation: Tissue proteomes from fatal COVID-19 identify disease subsets and dissect host immunopathologic signatures. In doing so, this may afford unique opportunities for therapeutic intervention. Funding Information: This work was funded by UK Research and Innovation (UKRI) (Coronavirus Disease [COVID-19] Rapid Response Initiative; MR/V028790/1 to C.D.L., D.A.D., and J.A.H.), LifeArc (through the University of Edinburgh STOPCOVID funding award, to K.D, D.A.D, C.D.L), The Chief Scientist Office (RARC-19 Funding Call, ‘Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis; COV/EDI/20/10’ to D.A.D, C.D.L, C.D.R, J.K.B and D.J.H), and Medical Research Scotland (CVG-1722-2020 to DAD, CDL, CDR, JKB, and DJH). C.D.L is funded by a Wellcome Trust Clinical Career Development Fellowship (206566/Z/17/Z). J.K.B. and C.D.R. are supported by the Medical Research Council (grant MC_PC_19059) as part of the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC-4C). C.D.R. is supported by an Edinburgh Clinical Academic Track (ECAT)/Wellcome Trust PhD Training Fellowship for Clinicians award (214178/Z/18/Z). J.A.H. is supported by the U.S. Food and Drug Administration (contract 75F40120C00085, Characterization of severe coronavirus infection in humans and model systems for medical countermeasure development and evaluation’). G.C.O is funded by an NRS Clinician award. N.N.G. is funded by a Pathological Society Award. A.R.A. is supported by a Cancer Research UK Clinician Scientist Fellowship award (A24867). Declaration of Interests: All authors have declared that no competing interests exist. Ethics Approval Statement: Written informed consent to undertake postmortem examinations was obtained from next-of-kin. Ethical approval was granted by the East of Scotland Research Ethics Service (16/ES/0084).

The α7 acetylcholine receptor (AChR) has been linked with the onset of psychotic symptoms and we hypothesized therefore that it might also be an autoimmune target. Here, we describe a new radioimmunoassay (RIA) using iodine 125-labelled α-bungarotoxin and membrane extract from transfected HEK293 cells expressing human α7 AChR. This RIA was used to analyze sera pertaining to a cohort of 711 subjects, comprising 368 patients diagnosed with schizophrenia spectrum disorders, 140 with bipolar disorder, 58 individuals diagnosed of other mental disorders, and 118 healthy comparison subjects. We identified one patient whose serum tested positive although with very low levels (0.2 nM) for α7 AChR-specific antibodies by RIA. Three out of 711 sera contained antibodies against iodine 125-labelled α-bungarotoxin, because they precipitated with it in the absence of α7 AChR. This first evidence suggests that autoantibodies against α7 AChR are absent or very rare in these clinical groups. ispartof: PLOS ONE vol:13 issue:12 ispartof: location:United States status: published

IntroductionThe aim of this study was to assess the impact of home-based telehealth monitoring on health outcomes, quality of life and costs over 12 months for patients with diabetes and/or chronic obstructive pulmonary disease (COPD) who were identified as being at high risk of readmission to hospital.MethodsThis pilot study was a randomised controlled trial combined with an economic analysis to examine the outcomes of standard care versus home-based telehealth for people with diabetes and/or COPD who were at risk of hospital readmission within one year. The primary outcomes were (i) hospital admission and length of stay (LOS); and (ii) health-related quality of life (HRQOL); and the secondary outcomes were (i) health-related clinical outcomes; (ii) anxiety and depression scores; and (iii) health literacy. The costs of the intervention and hospitalisations were included.ResultsA total of 86 and 85 participants were randomised to the intervention and control groups respectively. The difference between groups in hospital LOS was –3.89 (95% confidence interval (CI): –9.40, 1.62) days, and for HRQOL, 0.09 (95% CI: 0.05, 0.14) in favour of the telehealth monitoring group. There was a saving of AUD$6553 (95% CI: –12145, –961) in the cost of hospitalisation over 12 months, which offset the increased cost of tele-monitoring. The intervention group showed an improvement in anxiety, depression and health literacy at 12 months, and in the diabetes group, a reduction in microalbuminuria.DiscussionThe telehealth monitoring intervention improved patient's health outcomes and quality of life at no additional cost.

Narrative medicine has become a prominent method of developing more empathetic relationships between medical clinicians and patients, on the basis of a deeper understanding of the patient experience. Beyond its usefulness during clinical encounters, patient storytelling can inform processes and procedures in Advisory Councils, Committee Meetings, and Family as Faculty settings, leading to improved quality and safety in health care. Armed with a better understanding of the patient experience, clinicians and administrators can make decisions, hopefully in collaboration with patients, that will enrich the patient experience and increase satisfaction among patients, families, and staff. Patient and family storytelling is a key component of the collaboration that is ideal when an organization seeks to deliver patient- and family-centered care. Providing patients and families with training will make the narratives they share more powerful. Health care organizations will find that purposeful storytelling can be an invaluable aspect of a patient- and family-centered culture. Well-delivered storytelling will support quality- and safety-improvement efforts and contribute to improved patient satisfaction. This article provides instruction for teaching patients and families how to tell stories with purpose and offers advice about how to support patients, families, and clinicians participating in this effort.

Objectives: Schizophrenia is a neuropsychiatric disorder with a complex etiology and pathogenesis. While symptomatic treatment is available, there are no treatments that target the biological disease mechanisms. Recently, autoantibodies to neuronal cell surface antigens have been identified in patients with schizophrenia. Autoimmunity is affecting nearly 10% of the general population and its clinical spectrum varies from endocrine, musculoskeletal to neuropsychiatric syndromes. Since autoimmune patients frequently suffer from more than one autoimmune disease, we analyzed common autoantibodies as disease markers (or risk factors) to test the hypothesis that schizophrenia is correlated to autoimmunity. Methods: We tested sera from 232 schizophrenia, bipolar disorder and myasthenia gravis patients and healthy controls for the presence of autoantibodies by ELISA and immunofluorescence. The assays included: anti-nuclear antibodies (ANA), double-stranded DNA (dsDNA), and ribosomal P protein (RPP). ANA IFA screening was performed on ImmunGlo HEp-2 slides and the acquisition of images and interpretation of patterns was performed on the Immco i-Sight automated imaging system. Results: Prevalence of anti-dsDNA autoantibodies was found to be overall relatively high and to significantly differ between disease and control groups. Schizoaffective patients had highest titers of anti-dsDNA autoantibodies. The autoantibody titer anti-RPP differs significantly between the groups. Paranoid and disorganized patients had highest titers of anti-RPP autoantibodies. No significant difference was detected in the presence of ANA autoantibodies in the different study groups. Conclusions: We confirmed that a subgroup of schizophrenia patients had increased levels of autoantibodies. These findings are the first step to improve diagnosis and possibly treatment of schizophrenic patients with autoimmune etiology. Currently, control sera are being tested to match the sample size and the age and sex distribution of the disease group.

(1982). Computers in the Classroom. The Clearing House: A Journal of Educational Strategies, Issues and Ideas: Vol. 56, No. 2, pp. 82-85.

A survey was conducted to assess knowledge and attitudes of Nebraska K-12 teachers, Teachers College faculty and student teachers at the University of Nebraska-Lincoln. Results indicated Nebraska educators strongly favored instruction to foster computer literacy in secondary schools; however, the respondents did not feel qualified to teach computer literacy. Findings also reflected mixed feelings regarding computer-assisted instruction and computer-managed instruction. Information from the survey was used to design teacher preparation courses and inservice computer workshops to assist educators at all levels to use computers as instructional tools.

This study found a significant difference between cognitive styles and academic success of education students enrolled in instructional computer courses. Field-independent students had significantly higher scores in instructional computer courses than field dependent students. The impact of computers in education requires planners of preservice and inservice teacher training programs to design appropriate materials and training strategies to maximize the academic success of students in instructional computer courses.