A new animal model of spontaneous autoimmune peripheral polyneuropathy: implications for Guillain-Barré syndrome

BACKGROUND: Spontaneous autoimmune peripheral neuropathy including Guillain-Barré Syndrome (GBS) represents as one of the serious emergencies in neurology. Although pathological changes have been well documented, molecular and cellular mechanisms of GBS are still under-explored, partially due to short of appropriate animal models. The field lacks of spontaneous and translatable models for mechanistic investigations. As GBS is preceded often by viral or bacterial infection, a condition can enhance co-stimulatory activity; we sought to investigate the critical role of T cell co-stimulation in this autoimmune disease. RESULTS: Our previous study reported that transgene-derived constitutive expression of co-stimulator B7.2 on antigen presenting cells of the nervous tissues drove spontaneous neurological disorders. Depletion of CD4(+) T cells in L31 mice accelerated the onset and increased the prevalence of the disease. In the current study, we further demonstrated that L31/CD4(-/-) mice exhibited both motor and sensory deficits, including weakness and paresis of limbs, numbness to mechanical stimuli and hypersensitivity to thermal stimulation. Pathological changes were characterized by massive infiltration of macrophages and CD8(+) T cells, demyelination and axonal damage in peripheral nerves, while changes in spinal cords could be secondary to the PNS damage. In symptomatic L31/CD4(-/-) mice, the disruption of the blood neural barriers was observed mainly in peripheral nerves. Interestingly, the infiltration of immune cells was initiated in pre-symptomatic L31/CD4(-/-) mice, prior to the disease onset, in the DRG and spinal roots where the blood nerve barrier is virtually absent. CONCLUSIONS: L31/CD4(-/-) mice mimic most parts of clinical and pathological signatures of GBS in human; thus providing an unconventional opportunity to experimentally explore the critical events that lead to spontaneous, autoimmune demyelinating disease of the peripheral nervous system

Exploring Purpose as a Resource for Promoting Youth Program Engagement

Recent evidence that reflecting on one’s purpose in life increases engagement with academic tasks inspires questions about whether purpose interventions might enhance learning engagement more broadly. This potential may be particularly fruitful for programs serving youth from a wide range of ages wherein sustaining engagement may be challenging. Here, we explored whether a brief purpose writing intervention would increase adolescents’ engagement in 4-H programs. Participants (N = 130) were randomly assigned to write about either their sense of purpose or a control topic prior to the first day of a program, and they reported their level of program engagement at the end of that day. Regression analysis showed participant age was negatively associated with program engagement. However, writing about purpose halted this age-related decline in engagement. These preliminary findings situate purpose as a resource that can be leveraged to sustain older youths’ interest and engagement in youth programming

Assessing cardiometabolic parameter monitoring in inpatients taking a second-generation antipsychotic : the CAMI-SGA study – a crosssectional study

Objectives This study aims to determine the proportion of initial cardiometabolic assessment and its predicting factors in adults with schizophrenia, bipolar disorder or other related diagnoses for whom a second-generation antipsychotic was prescribed in the hospital setting. Design Cross-sectional study. Setting The psychiatry unit of a Canadian tertiary care teaching hospital in Montreal, Canada. Participants 402 patients with aforementioned disorders who initiated, restarted or switched to one of the following antipsychotics: clozapine, olanzapine, risperidone, paliperidone or quetiapine, between 2013 and 2016. Primary outcome measures We assessed the proportion of cardiometabolic parameters monitored. Secondary outcome measures We identified predictors that influence the monitoring of cardiometabolic parameters and we assessed the proportion of adequate interventions following the screening of uncontrolled blood pressure and fasting glucose or glycated haemoglobin (HbA1c) results. Results Only 37.3% of patients received monitoring for at least three cardiometabolic parameters. Blood pressure was assessed in 99.8% of patients; lipid profile in 24.4%; fasting glucose or HbA1c in 33.3% and weight or body mass index in 97.8% of patients while waist circumference was assessed in 4.5% of patients. For patients with abnormal blood pressure and glycaemic values, 42.3% and 41.2% subsequent interventions were done, respectively. The study highlighted the psychiatric diagnosis (substance induced disorder OR 0.06 95% CI 0.00 to 0.44), the presence of a court-ordered treatment (OR 0.79 95% CI 0.35 to 1.79) and the treating psychiatrist (up to OR 34.0 95% CI 16.2 to 140.7) as predictors of cardiometabolic monitoring. Conclusions This study reports suboptimal baseline cardiometabolic monitoring of patients taking an antipsychotic in a Canadian hospital. Optimising collaboration within a multidisciplinary team may increase cardiometabolic monitoring

THE EFFECTS OF CONFLICTING TREATMENT APPROACHES ON THE OPERATIONS AND PROCEDURES OF TWO TYPES OF METHADONE TREATMENT PROGRAMS: A STUDY IN INSTITUTIONAL ANALYSIS (ORGANIZATIONAL THEORY, DETOXIFICATION, DRUG ABUSE)

Governmental mandates for the detoxification of methadone clients resulted in the emergence of a methadone detoxification treatment modality, which was adopted by several programs with a therapeutic community orientation. The use of methadone, however, contradicts the drug-free orientation of therapeutic community treatment. Assumptions derived from organizational theory as well as the findings of previous research suggested that such contradictory mandates would result in the emergence of contradictions in the operations of these programs. Thus, it was expected that the adoption of methadone treatment by therapeutic communities would result in organizational strain (i.e., dissonance among staff regarding treatment approaches). It was expected that such organizational strain would neutralize organizational control over clients, thus resulting in a lowered rate of client retention. It was finally expected that the organizational strain resulting from the combination of methadone and therapeutic community treatment would be reflected in adaptive changes in organizational structure. Methadone programs with a therapeutic community orientation were compared with methadone programs that did not feature such an orientation through an analysis of interviews collected through a survey of staff employed in a sample of programs in New York City. Data on client characteristics (i.e., age, sex, ethnicity, and time in treatment) were also analysed. Findings indicated that staff in methadone programs with a therapeutic community orientation were no more likely to experience organizational strain than were staff in methadone programs without such an orientation, and changes in organizational structure were as likely to occur in the latter group as in the former. However, methadone programs with a therapeutic community orientation did experience a lower rate of client retention. Moreover, the retention rates of methadone programs with a therapeutic community orientation declined over time while the rates of the other methadone programs did not. The findings suggested that the programs interpreted contradictory mandates in such a way so that potentially conflicting treatment procedures were incorporated into the programs\u27 underlying treatment orientation. It is suggested that the findings are relevant to three areas of study: (1) studies of organizations; (2) studies of program implementation and evaluation; and (3) studies of the effectiveness of methadone treatment programs

Improving Electrical System Management for the Town of Boylston, MA

This project was intended to assist the Boylston Municipal Light Department in modernizing their management and record keeping processes. After compiling information about the town's electric infrastructure, our project group developed a sustainable computerized system that allows for efficient record-keeping and information updating practices for the electric infrastructure. Furthermore, we made strong recommendations about how to better organize and execute daily maintenance tasks in a more proficient manner

Gait Efficiency Analysis Using Three Axis Force Plate

For approximately the last hundred years people have been interested in analyzing human gait. Using many different measurement techniques, researchers have been looking for ways to increase efficiency while minimizing injuries. The intent of this project is to find out how varying human stride length affects the overall quality of the gait. With a three axis force plate designed and fabricated by the group, various data sets were recorded for each individual in the subject pool. Data were recorded for each subject using their natural stride length, followed by both under striding and over striding gaits. Using the data gathered by the force plate along with body geometry and velocities, it was possible to find the optimal stride length for each individual

Iron Prevents the Development of Experimental Cerebral Malaria by Attenuating CXCR3-Mediated T Cell Chemotaxis

<div><p>Cerebral malaria is a severe neurological complication of <i>Plasmodium falciparum</i> infection. Previous studies have suggested that iron overload can suppress the generation of a cytotoxic immune response; however, the effect of iron on experimental cerebral malaria (ECM) is yet unknown. Here we determined that the incidence of ECM was markedly reduced in mice treated with iron dextran. Protection was concomitant with a significant decrease in the sequestration of CD4⁺ and CD8⁺ T cells within the brain. CD4⁺ T cells demonstrated markedly decreased CXCR3 expression and had reduced IFNγ-responsiveness, as indicated by mitigated expression of IFNγR2 and T-bet. Additional analysis of the splenic cell populations indicated that parenteral iron supplementation was also associated with a decrease in NK cells and increase in regulatory T cells. Altogether, these results suggest that iron is able to inhibit ECM pathology by attenuating the capacity of T cells to migrate to the brain.</p></div

The Expression of Genes Involved in T Cell Chemotaxis are Attenuated by Parenteral Iron Supplementation.

<p>The expression of genes involved in T cell chemotaxis is shown for the brain (<b>a</b>) and the spleen (<b>b</b>) on day 7 post-infection. mRNA levels were normalized to <i>Gusb</i>. 2 samples pooled from 6 mice (3 mice per sample) were used for each group. UI = uninfected, I = infected, FeD = iron dextran, PBS = control.</p