M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator

Abstract Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM ...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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ConclusionsOur findings suggest that trauma-exposed individuals exhibit information processing alterations in response to neutral environmental stimuli that may be related to a general pattern of heightened activity of the Salience Network. Implications for the neurobiological model of PTSD and PTSD psychotherapy are discussed.
Source: Neuropsychologia - Category: Neurology Source Type: research
Conclusions: Among male refugees living in precarious conditions in a Greek refugee camp, frequency of participation in an 8-week exercise and sport training program seemed to have the potential to positively impact refugees’ health. Due to the pre-experimental study design, our results must be interpreted with caution.
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
Conclusions: This case demonstrates the effectiveness of lifestyle interventions and psychospiritual support to enable dramatic clinical change without withdrawal syndrome after cessation of medication. More important, the initial failed tapering underpins the notion that a diligent meditation practice may be necessary to heal root-cause drivers of psychiatric symptoms and withdrawal syndrome. The results may serve to inform practitioners assisting patients who wish to discontinue benzodiazepine and other psychotropic medications or patients who would like to try a nonpharmaceutical approach as a first-line therapy. PM...
Source: Advances in Mind Body Medicine - Category: Psychiatry Tags: Adv Mind Body Med Source Type: research
Did the movie Joker portray mental illness correctly and does it matter? We passionately go over the movie Joker from the lense of people living with mental illness and discuss whether or not there are implications of making a movie like this. Does it help us or hurt us? What if it does both? Listen in to hear Gabe’s freakishly good recollection of scenes from the movie as Jackie struggles to separate entertainment from reality.  Spoiler Alert: You don’t need to see Joker to appreciate this conversation but we do go over the plot and reveal some important scenes from the movie. (Transcript Available Below)...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: A Bipolar, A Schizophrenic, and a Podcast Antidepressant Antipsychotic Depression Minding the Media Not Crazy Podcast Source Type: blogs
The ability of resting-state functional MRI (fMRI) to pinpoint reduced brain...Read more on AuntMinnie.comRelated Reading: fMRI connects words to brain activity fMRI may speed up diagnosis of autism fMRI links imaging biomarker to PTSD treatment response PET, fMRI shed light on alcohol's effects on brain Machine learning, fMRI unlock cellular brain properties
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
Post-traumatic fungal infections are an uncommon (2-17% of all fungal infections are post-traumatic), yet life threatening complication secondary to major traumatic injury, that develop when fungal spores inoculate damaged tissue at the injury or wound site, leading to aggressive proliferation of spores and potential angioinvasion. [1-5] Sometimes characterized as a concomitant condition of a major traumatic injury, post-traumatic fungal infections can compromise the immune system, rapidly causing vessel thrombosis and tissue necrosis from a wound site or systemically.
Source: Injury - Category: Orthopaedics Authors: Source Type: research
Tibial plateau fractures account for 1 –2% of all fractures and 8% of fractures in the elderly [1, 2]. Fractures of the tibial plateau typically involve metaphyseal and articular comminution. The goal of treatment is anatomic reduction of the articular surface, the proper alignment of the lower extremity, stable fixation and reducing t he risk of post-traumatic osteoarthritis [3, 4].
Source: Injury - Category: Orthopaedics Authors: Source Type: research
Posttraumatic stress disorder (PTSD) is a common, debilitating disorder that affects ∼8% of the U.S. population, with even higher estimates of ∼20%, in U.S. veterans of Afghanistan and Iraq (1). Although psychotherapeutic and pharmacological interventions can significantly reduce PTSD symptoms, there remains considerable room for improvement (2,3). Only two pharmacological thera peutics, sertraline and paroxetine, have been approved by the U.S. Food and Drug Administration (FDA) for PTSD (2). Response to these selective serotonin reuptake inhibitors rarely exceeds 60%, and only 20% to 30% of patients achieve comple...
Source: Biological Psychiatry - Category: Psychiatry Authors: Tags: Correspondence Source Type: research
Trauma or injury to the dentition and supporting tissues is associated with pain and discomfort, as expected, that may present immediately, shortly afterwards, or within a few days. Pain is an essential response to injury because it allows the organism to develop avoidance behavior to potential threats and helps the organism to avoid usage of the injured organ during the healing process. Not only does external trauma induce pain, but also essential invasive dental procedures such as extractions, dental implant insertions, root canal treatments, and oral surgeries are accompanied by similar post-surgical (post-traumatic) pain.
Source: Journal of Endodontics - Category: Dentistry Authors: Tags: 2018 Meeting of the World Congress on Dental Traumatology Source Type: research
The objective of this study was to investigate the efficacy of BATD across 2 DSM-5 diagnoses: major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Methods: Participants were recruited from October 2014 to December 2017. Thirty-one participants were referred from primary care and consented to receive a 12-session trial of BATD. Participants endorsed criteria consistent with a principal diagnosis of either MDD (n = 20) or PTSD (n = 11). Self-report measures were completed at baseline and immediately posttreatment to monitor treatment progress in symptoms of PTSD and MDD. Results: Twelve of the 31...
Source: The Primary Care Companion for CNS Disorders - Category: Primary Care Tags: Prim Care Companion CNS Disord Source Type: research
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