The cholesterol hypothesis: time for the obituary?

The cholesterol hypothesis links cholesterol intake and blood levels to cardiovascular disease. It has had enormous impact on health care and society during decades, but has little or no scientific backing that is relevant for the human species. Apparently, the hypothesis is false and should be buried.     

Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals.     

Risk factors related to recurrence in inguinal hernia repair: a retrospective analysis

The aim of this study was to analyze and evaluate the long-term recurrence rate and risk factors for inguinal hernia recurrence in patients treated by the Shouldice suture repair. A total of 293 hernias treated by Shouldice suture technique in 1992 were studied retrospectively. After a 10-year follow-up, 15 potential risk factors for recurrence were assessed in 142 patients undergoing 171 Shouldice repairs. Recurrent hernias showed a significantly higher (22.0%) recurrence rate than primary inguinal hernias (7.7%). Furthermore, an age of more than 50 years, smoking, and the presence of two or more similarly affected relatives were found to be independent risk factors for recurrence. The present study underlines the importance of patient-related risk factors for the development of a recurrent inguinal hernia. Patients at risk should preoperatively be identified in order to improve treatment by, for example, the application of mesh techniques.     

Deleterious effect of zinc in a pig model of acute endotoxemia.

By antiapoptotic effects and the induction of the heat-shock response, zinc is supposed to be a promising means of therapy during sepsis. As zinc also stimulates the expression of proinflammatory cytokines, its administration during the proinflammatory stage of septic shock might have adverse effects. Therefore, this study analyzes the influence of zinc during the acute phase of endotoxemia. In a pig model of acute endotoxemia, animals were divided into two groups: group I (n = 5) with saline treatment and group II (n = 5) with zinc treatment in close succession to lipopolysaccharide (LPS) (1.0 mu g/kg Escherichia coli endotoxin WO 111:B4). Hemodynamic and pulmonary monitoring was followed by combined reflection photometry, pulse oxymetry, blood gas samples, and temperature measurement. Plasma concentrations of tumor necrosis factor (TNF)alpha and interleukin (IL)-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). Morphology included the weight of the lungs, the width of the alveolar septae, and the paracentral necrosis rate of the liver. After LPS infusion, group II (zinc) showed an impressive and significant deterioration of all pulmonary and most of the hemodynamical parameters compared to group I (saline). Levels of TNFalpha and IL-6 measured were significantly higher after zinc treatment. In accordance, we found significant more morphologic damages in group II (zinc). The almost simultaneous infusion of zinc and LPS complementary induced proinflammatory effects with a deleterious outcome. The same potentials characterizing zinc as a promising tool of prophylactic therapy in sepsis seem to ban its use during the acute phase.     

Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease

Sickle cell disease (SCD) is characterized by intravascular hemolysis and inflammation coupled to a 400-fold greater incidence of invasive pneumococcal infection resulting in fulminant, lethal pneumococcal sepsis. Mechanistically, invasive infection is facilitated by a proinflammatory state that enhances receptor-mediated endocytosis of pneumococci into epithelial and endothelial cells. As statins reduce chronic inflammation, in addition to their serum cholesterol-lowering effects, we hypothesized that statin therapy might improve the outcome of pneumococcal infection in SCD. In this study, we tested this hypothesis in an experimental SCD mouse model and found that statin therapy prolonged survival following pneumococcal challenge. The protective effect resulted in part from decreased platelet-activating factor receptor expression on endothelia and epithelia, which led to reduced bacterial invasion. An additional protective effect resulted from inhibition of host cell lysis by pneumococcal cholesterol-dependent cytotoxins (CDCs), including pneumolysin. We conclude therefore that statins may be of prophylactic benefit against invasive pneumococcal disease in patients with SCD and, more broadly, in settings of bacterial pathogenesis driven by receptor-mediated endocytosis and the CDC class of toxins produced by Gram-positive invasive bacteria.