Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, ␣ 1 -acid-glycoprotein (AAG), ␣ 1 -antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P ‫؍‬ 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P ‫؍‬ 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P ‫؍‬ 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P ‫؍‬ 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.Hypercholesterolemia, lipid metabolism imbalances, hypertension, age, gender, body mass index, diabetes mellitus, homocysteine, stress, and smoking are widely accepted as "classic" risk factors for development of cardiovascular disease (CVD). However, it has also become clear that the contribution of these factors cannot be supported in 25 to 50% of subjects who develop CVD and cerebrovascular disease (39, 53). These observations have intensified initiatives to identify additional risk factors for the development of atherosclerosis and vascular ischemic diseases. Recent evidence indicates that the development of CVD correlates with elevated levels of C-reactive protein (CRP) (25,30,35,45,54,55) and soluble cellular adhesion molecules (CAM) (27,48,56,76) which are produced in response to cellular damage. These observations have led to a reexamination of one of the earliest theories regarding the etiology of atherosclerosis and coronary heart disease (CHD): inflammatory processes which may arise in association with infection (39, 42).In the mid-1800s, Virchow drew attention to the presence of two distinct lesions along arterial vessel walls: the classical "fatty streak" and a second ...

SummaryThe dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experiments to address these questions. Ubiquitination of mitochondrial fragments is required the earliest, followed by auto-phosphorylation of TBK1. Next, early essential autophagy proteins FIP200 and ATG13 act at different steps, whereas ULK1 and ULK2 are dispensable. Receptors act temporally and mechanistically upstream of ATG13 but downstream of FIP200. The VPS34 complex functions at the omegasome step. ATG13 and optineurin target mitochondria in a discontinuous oscillatory way, suggesting multiple initiation events. Targeted ubiquitinated mitochondria are cradled by endoplasmic reticulum (ER) strands even without functional autophagy machinery and mitophagy adaptors. We propose that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes.

Tenascin-C (TNC), a major component of the extracellular matrix, is strongly upregulated after injuries of the central nervous system (CNS) but its role in tissue repair is not understood. Both regeneration promoting and inhibiting roles of TNC have been proposed considering its abilities to both support and restrict neurite outgrowth in vitro. Here, we show that spontaneous recovery of locomotor functions after spinal cord injury is impaired in adult TNC-deficient (TNC(-/-)) mice in comparison to wild-type (TNC(+/+)) mice. The impaired recovery was associated with attenuated excitability of the plantar Hoffmann reflex (H-reflex), reduced glutamatergic input, reduced sprouting of monaminergic axons in the lumbar spinal cord and enhanced post-traumatic degeneration of corticospinal axons. The degeneration of corticospinal axons in TNC(-/-) mice was normalized to TNC(+/+) levels by application of the alternatively spliced TNC fibronectin type III homologous domain D (fnD). Finally, overexpression of TNC-fnD via adeno-associated virus in wild-type mice improved locomotor recovery, increased monaminergic axons sprouting, and reduced lesion scar volume after spinal cord injury. The functional efficacy of the viral-mediated TNC indicates a potentially useful approach for treatment of spinal cord injury.

SUMMARY:Tinnitus affects 10% of the US general population and is a common indication for imaging studies. We describe a sequential compartment-based diagnostic approach, which simplifies the interpretation of imaging studies in patients with tinnitus. The choice of the initial imaging technique depends on the type of tinnitus, associated symptoms, and examination findings. Familiarity with the pathophysiologic mechanisms of tinnitus and the imaging findings is a prerequisite for a tailored diagnostic approach by the radiologist.ABBREVIATIONS AV ϭ arteriovenous; AVF ϭ arteriovenous fistula; AVM ϭ arteriovenous malformation; CPA ϭ cerebellopontine angle; DSA ϭ digital subtraction angiography; IAC ϭ internal auditory canal; ICA ϭ internal carotid artery; IIH ϭ idiopathic intracranial hypertension; MD ϭ Mé niè re disease; NSAIDs ϭ nonsteroidal anti-inflammatory drugs; PSA ϭ persistent stapedial artery; TMJ ϭ temporomandibular joint.

Suicides in the over 65 year olds may be decreased by changes in prescription practice. Paracetamol, co-proxamol, tricyclic antidepressants and benzodiazepines should be prescribed with caution to the elderly with depression or at high risk of depression.