Partial MHC class II constructs inhibit MIF/CD74 binding and downstream effects

MIF and its receptor, CD74, are pivotal regulators of the immune system. Here, we demonstrate for the first time that partial MHC class II constructs comprised of linked β1α1 domains with covalently attached antigenic peptides (also referred to as recombinant T‐cell receptor ligands — RTLs) can inhibit MIF activity by not only blocking the binding of rhMIF to immunopurified CD74, but also downregulating CD74 cell‐surface expression. This bifunctional inhibition of MIF/CD74 interactions blocked downstream MIF effects, including enhanced secretion of proinflammatory cytokines, anti‐apoptotic activity, and inhibition of random migration that all contribute to the reversal of clinical and histological signs of EAE. Moreover, we demonstrate that enhanced CD74 cell‐surface expression on monocytes in mice with EAE and subjects with multiple sclerosis can be downregulated by humanized RTLs, resulting in reduced MIF binding to the cells. Thus, binding of partial MHC complexes to CD74 blocks both the accessibility and availability of CD74 for MIF binding and downstream inflammatory activity.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Which is the Most Appropriate Disconnection Surgery for Refractory Epilepsy in Childhood?

Children with unilobar or multilobar pathology issuing in refractory epilepsy are potential candidates for surgical treatment. Extensive surgery results in good seizure control, but it also increases the risk of neurological deficits as well as motor and mental problems. We reviewed the cases of 19 children with refractory epilepsy treated surgically at Osaka University Hospital. Four of the 19 patients underwent temporal disconnection, 2 underwent occipital lobectomy, 4 underwent temporoparietooccipital disconnection, 6 underwent functional hemispherotomy, and 3 underwent corpus callosotomy. A good surgical outcome, i.e., Engel’s class I or II, was achieved in 12 (63%) of the 19 patients. Excellent surgical outcomes and satisfactory motor and mental development were achieved in 4 patients who underwent temporoparietooccipital disconnection. The outcomes of functional hemispherectomy were also satisfactory. The outcomes of temporal disconnection and corpus callosotomy were poor in comparison to outcomes of the other procedures. We believe that better surgical outcomes would have been achieved with temporoparietooccipital disconnection in some cases treated by temporal disconnection or occipital resection. Adequate extensive surgical procedures should be considered for refractory childhood epilepsy arising from unilobar or multilobar pathology.     

Allowing brief delays in responding improves event-based prospective memory for young adults living with HIV disease

Event-based prospective memory (PM) tasks require individuals to remember to perform an action when they encounter a specific cue in the environment, and they have clear relevance for daily functioning for individuals with HIV. In many everyday tasks, not only must the individual maintain the intent to perform the PM task, but the PM task response also competes with the alternative and more habitual task response. The current study examined whether event-based PM can be improved by slowing down the pace of the task environment. Fifty-seven young adults living with HIV performed an ongoing lexical decision task while simultaneously performing a PM task of monitoring for a specific word (which was focal to the ongoing task of making lexical decisions) or syllable contained in a word (which was nonfocal). Participants were instructed to refrain from making task responses until after a tone was presented, which occurred at varying onsets (0–1600 ms) after each stimulus appeared. Improvements in focal and nonfocal PM accuracy were observed with response delays of 600 ms. Furthermore, the difference in PM accuracy between the low-demand focal PM task and the resource-demanding nonfocal PM task was reduced by half across increasingly longer delays, falling from 31% at 0-ms delay to only 14% at 1600-ms delay. The degree of ongoing task response slowing for the PM conditions, relative to a control condition that did not have a PM task and made lexical decisions only, also decreased with increased delay. Overall, the evidence indicates that delaying the task responses of younger HIV-infected adults increased the probability that the PM relevant features of task stimuli were adequately assessed prior to the ongoing task response, and by implication that younger HIV infected adults can more adequately achieve PM goals when the pace of the task environment is slowed down.     

An epidemiologic investigation of homicides at Fort Carson, Colorado: summary of findings

In response to an apparent clustering of homicides at Fort Carson, Colorado, the U.S. Army Public Health Command (formerly the U.S. Army Center for Health Promotion and Preventive Medicine) Behavioral and Social Health Outcomes Program conducted a multidisciplinary epidemiologic consultation to identify factors contributing to violent behavior among soldiers at Fort Carson. This article summarizes the findings of the epidemiologic consultation report as provided to the Secretary of the Army and the Fort Carson Senior Mission Commander and released in its entirety publicly July 2009 and elaborates on the mixed-methods analytic approach used to study a complex behavioral issue at the community level. To aid in answering the key study questions, six study arms were designed and carried out: (1) index case analysis, (2) confinee interviews, (3) analysis of installation-level trends, (4) retrospective cohort analysis, (5) soldier focus groups and interviews, and (6) aggression risk factors survey. Although not conclusive, the findings suggest a combination of individual, unit, and environmental factors converged to increase the risk of violent behaviors, which made clustering of negative outcomes more likely.     

We just don't talk about it: Men living with urinary incontinence and multiple sclerosis

For people with multiple sclerosis (MS), urinary incontinence can become central to their experiences of managing the consequences of the disease. The Research Unit at the Royal District Nursing Service in South Australia conducted a study between October and December 1998 that aimed to understand how people living with multiple sclerosis manage urinary incontinence. This paper reports the findings from a participatory action research group consisting of four men who lived with MS and urinary incontinence, two continence nurse advisors (CNA) and the researcher. Incontinence was found to be a subject that men had found difficult to talk about previously. Themes that emerged from the conversations with the men were: planning your life around toilets; today will not be the same as tomorrow; managing myself; and motivated to make changes. The men and the CNA experienced a valuable exchange of knowledge about living with incontinence. We consider it essential that the voices of these men are clearly heard so that health-care providers may be responsive and sensitive to their clients' needs.     

Visualising emergency department capacity in an ‘Emergency Department Capacity Clock’: A novel tool to assess and communicate overcrowding and access block

Hospital‐wide engagement is required to alleviate the problem of ED crowding and its associated adverse effects. To this end, the article describes a novel visualisation termed ‘the ED Capacity Clock’, which can be formatted using business intelligence software. This radial diagram represents ED capacity and its consumption in a format that can be understood intuitively and at a glance. The ED Capacity Clock is designed to promote common understanding and discussion between relevant hospital services and also acts as an auditing tool to monitor processes implemented to alleviate ED crowding.     

Metabolomics reveals the depletion of intracellular metabolites in HepG2 cells after treatment with gold nanoparticles

Studies on the safety of gold nanoparticles (GNPs) are plentiful due to their successful application in drug delivery and treatment of diseases in trials. Cytotoxicity caused by GNPs has been studied on the physiological and biochemical level; yet, the effect of GNPs (particularly gold nano-spheres) on the metabolome of living organisms remains understudied. In this investigation, metabolomics was used to comprehensively study the metabolic alterations in HepG2 cells caused by GNPs; and to investigate the role of representative GNP coatings. GNPs were synthesized, coated and characterized before use on HepG2 cell cultures. Cells were treated for 3?h with citrate-, poly-(sodiumsterene sulfunate)-, and poly-vinylpyrrolidone (PVP)-capped GNPs, respectively. The internalization of the different GNPs and their effect on mitochondrial respiration and the metabolome were studied. Results indicated that the PVP-capped GNPs internalized more and also caused a more observable effect on the metabolome. Conversely, it was the citrate- and poly-(sodiumsterene sulfunate) coated particles that influenced ATP production in addition to the metabolomic changes. A holistic depletion of intracellular metabolites was observed regardless of GNP coating, which hints to the binding of certain metabolites to the particles.