The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats

Chronic kidney disease and coenzyme Q10 supplementation

Among the potential causes of chronic kidney disease (CKD), mitochondrial respiratory chain (MRC) dysfunction, oxidative stress and inflammation have been implicated as contributor factors to the pathogenesis of this disorder. It is thought that CoQ10 supplementation may offer some therapeutic potential in the treatment of patients with CKD, since CoQ10 has a key role in normal MRC function, as well as having antioxidant and anti-inflammatory action. This article will outline the current knowledge on the use of CoQ10 in the treatment of CK

Recovery expectations of neck pain patients do not predict treatments outcome in manual therapy.

Patient recovery expectations can predict treatment outcome. Little is known about the association of patient recovery expectations on treatment outcome in patients with neck pain consulting a manual therapist. This study evaluates the predictive value of recovery expectations in neck pain patients consulting manual therapists in the Netherlands. The primary outcome measure 'recovery' is defined as 'reduction in pain and perceived improvement'. A prospective cohort study a total of 1195 neck pain patients. Patients completed the Patient Expectancies List (PEL) at baseline (3 item questionnaire, score range from 3 to 12), functional status (NDI), the Global Perceived Effect (GPE) for recovery (7-points Likert scale) post treatment and pain scores (NRS) at baseline and post treatment. The relationship between recovery expectancy and recovery (dichotomized GPE scores) was assessed by logistic regression analysis. Patients generally reported high recovery expectations on all three questions of the PEL (mean sumscores ranging from 11.3 to 11.6). When adjusted for covariates the PEL sum-score did not predict recovery (explained variance was 0.10 for the total PEL). Separately, the first question of the PEL showed predictive potential (OR 3.7; 95%CI 0.19-73.74) for recovery, but failed to reach statistical significance. In this study patient recovery expectations did not predict treatment outcome. Variables predicting recovery were recurrence and duration of pain. The precise relationship between patient recovery expectations and outcome is complex and still inconclusive. Research on patient expectancy would benefit from more consistent use of theoretical expectancy and outcome models