Loss of TLR3 and its downstream signaling accelerates acinar cell damage in the acute phase of pancreatitis

Background

Acute pancreatitis is accompanied by acinar cell damage releasing potential toll-like receptor 3 (TLR3) ligands. So far, TLR3 is known as a pattern recognition receptor in the immune signaling cascade triggering a type I interferon response. In addition, TLR3 signaling contributes to programmed cell death through the activation of caspase 8. However, the functional role of TLR3 and its downstream toll-like receptor adaptor molecule 1 (TICAM1) in the inflamed pancreas is unknown.

The Outcome of Coxsackievirus B3-(CVB3-) Induced Myocarditis is Influenced by the Cellular Immune Status

Mice develop a marked age-related susceptibility to myocardial coxsackievirus B3 (CVB3) infections. The lesions observed in mice resemble closely those seen in the human disease. Experimental murine models of CVB3-induced myocarditis have shown that both, host and viral genetic factors, can influence susceptibility to the infection as well as the persistence and progression of the disease. Recently, we have shown that CD4 T cell-deficient MHC Class II knockout mice develop a strong fibrosis with virus persistence in the heart tissue and without production of neutralizing antibodies. To examine the role of CD4+ T cells and especially the role of the T helper 1 cell response for the outcome and pathogenesis of CVB3-induced myocarditis in more detail, 2 different mouse strains with identical genetic background (H-2b) were infected with CVB3-Mü/J (Nancy strain). Immunocompetent C57BL/6 mice and mice with targeted disruption of interleukin (IL-)4 gene (IL-4-/- mice) developed a severe acute myocarditis on day 7 post infection (p.i.). The CVB3-induced inflammation was cured until the 21st day p.i. in hearts of C57BL/6 mice. IL-4-/- mice with insufficient T helper-2 cell immune response developed a severe myocardial damage between day 7 and 21 p.i. with prolonged virus persistence in the heart tissue. Therefore, we suggest that despite an obvious normal T helper-1 cell cytokine pattern, IL-4-/- mice are more susceptible to long-term heart muscle injuries after infection with CVB3.     

Effects of chitosan and bioactive glass modifications of knitted and rolled polylactide‐based 96/4 L/D scaffolds on chondrogenic differentiation of adipose stem cells

The performance of biodegradable knitted and rolled 3‐dimensional (3D) polylactide‐based 96/4 scaffolds modified with bioactive glass (BaG) 13‐93, chitosan and both was compared with regard to the viability, proliferation and chondrogenic differentiation of rabbit adipose stem cells (ASCs). Scaffold porosities were determined by micro‐computed tomography (μCT). Water absorption and degradation of scaffolds were studied during 28‐day hydrolysis in Tris‐buffer. Viability, number and differentiation of ASCs in PLA96/4 scaffolds were examined in vitro. The dimensions of the scaffolds were maintained during hydrolysis and mass loss was detected only in the BaG13‐93 containing scaffolds. ASCs adhered and proliferated on each scaffold type. Cell aggregation and expression of chondral matrix components improved in all scaffold types in chondrogenic medium. Signs of hypertrophy were detected in the modified scaffolds but not in the plain PLA96/4 scaffold. Chondrogenic differentiation was most enhanced in the presence of chitosan. These findings indicate that the plain P scaffold provided a good 3D‐matrix for ASC proliferation whereas the addition of chitosan to the PLA96/4 scaffold induced chondrogenic differentiation independent of the medium. Accordingly, a PLA96/4 scaffold modified by chitosan could provide a functional and bioactive basis for tissue‐engineered chondral implants. Copyright © 2012 John Wiley & Sons, Ltd.     

Delayed Haematological recovery after autologous stem cell transplantation is associated with favourable outcome in acute myeloid leukaemia

Autologous stem cell transplantation (ASCT) is applied to consolidate first remission in patients with acute myeloid leukaemia (AML). However, outcome after ASCT widely varies among AML patients. We analyzed the prognostic significance of haematological recovery for neutrophils [absolute neutrophil count (ANC) >1·0 × 10⁹/l] and platelets (platelet count >20·0 × 10⁹/l), stratifying at day 20 after ASCT in 88 consecutive and homogeneously treated AML patients in first remission. We observed that patients with delayed recovery had better overall survival (OS; ANC: P < 0·0001 and platelets: P = 0·0062) and time to progression (TTP; ANC: P = 0·0003 and platelets: P = 0·0125). Delayed recovery was an independent marker for better OS and TTP in a multivariate analysis including age, gender, number of transfused CD34+ cells, cytogenetics, FLT3‐internal tandem duplication and NPM1 mutation. Our results suggest that delayed neutrophil and platelet recovery is associated with longer OS and TTP in AML patients consolidated with ASCT in first remission.     

Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) has been shown to cause a reduction in quality of life. This study examines the extent of different PCOS symptoms on quality-of-life, psychosocial well-being and sexual satisfaction. METHODS: Complete metabolic, hormonal, clinical and psychosocial data were obtained from a total of 120 women with PCOS. Patients were compared with 50 healthy women to establish reductions in quality-of-life and emotional well-being. In addition, the correlation between psychosocial variables and the major clinical PCOS features obesity (body mass index (BMI)), excessive body hair (hirsutism score), acne, hyperandrogenism (serum testosterone levels), disturbed insulin regulation (area under the insulin response curve and homeostasis model assessment of insulin resistance), menstrual cycle disturbances and infertility were analyzed. RESULTS: PCOS patients showed significant reductions in quality-of-life, increased psychological disturbances, and decreased sexual satisfaction when compared with healthy controls. BMI and hirsutism scores, but not the presence of acne, were associated with physical aspects of quality-of-life and sexual satisfaction. No clear effect of androgens or insulin resistance on psychosocial variables was detected. Similarly, the type of menstrual cycle disturbances or infertility had no impact on psychological well-being. CONCLUSION: In PCOS, changes in appearance, particularly obesity and hirsutism, reduce physical dimensions of quality-of-life and decrease sexual satisfaction. The role of biochemical, endocrine and metabolic parameters as well as menstrual irregularities and infertility appeared to be less important. Clinicians should pay attention to the psychosocial dimensions of PCOS on an individual basis, regardless of symptom severity or treatment response.     

Identification of successful catheter ablation sites in patients with ventricular tachycardia based on electrogram characteristics during sinus rhythm

BACKGROUND: Zones of slow conduction facilitate reentry, the major mechanism of ventricular tachycardia (VT) after myocardial infarction (MI). Identification of these zones during sinus rhythm (SR) is desirable for radiofrequency (RF) catheter ablation of VT. Local conduction velocity may correlate with electrogram duration. OBJECTIVES: The purpose of this study was to revise the definition of normal electrogram characteristics and to reevaluate the significance of low-amplitude, long-duration electrograms recorded during SR to select RF catheter ablation sites in patients with VT. METHODS: Electroanatomic mapping was performed during SR in 10 control patients with normal left ventricles (LVs) and in 10 patients with stable VT after MI. From the controls, reference values for electrogram amplitude, duration (first peak to last peak distance), and fragmentation (positive deflection) were derived. In patients after MI, areas with signals exceeding these values were annotated and related to successful ablation sites. RESULTS: Ninety-five percent of normal LV electrograms were > or =1.0 mV and < or =28 ms (range 5-39 ms) and all had < or =4 deflections. Based on these results, cutoff values were set at 1 mV, four deflections, and 40 ms. In infarcted hearts, 653 electrograms (44%) were <1.0 mV and of these, 303 were > or =40 ms with >4 deflections and restricted to circumscribed areas. Twenty-seven of 28 targeted VTs remained noninducible after RF catheter ablation within these areas, resulting in 86% sensitivity and 94% specificity for low-amplitude, long-duration electrograms predicting successful ablation sites. CONCLUSION: Identification of successful RF target areas during SR in patients with VT is feasible with high sensitivity and specificity using a mapping strategy based on voltage and duration criteria.     

Do mobility,cognitive functioning,and depressive symptoms mediate the association between social activity and mortality risk among older men and women?

Social activity and health correlate in old age, but less is known about what explains this association. The aim of this study was to investigate whether mobility, cognitive functioning, and depressive symptoms mediate the association between social activity and mortality risk, or whether they alternatively should be considered as prerequisites for social activity in older Finnish men and women. In 1988, 406 men and 775 women aged 65–84 years took part in face-to-face interviews about their health, socioeconomic status, and social activities. Confirmatory factor analyses were used to form latent variables describing collective and productive social activity. Latent variable models were used to investigate the possible pathways among social activity, mobility, cognitive functioning, depressive symptoms, and mortality risk. In the 21-year follow-up, 89 % of men and 81 % of women had died. Collective and productive social activity correlated with a lower risk for mortality among men and women. Part of the association between social activity and mortality was mediated by mobility. Cognitive functioning and depressive symptoms were not mediators in the association. Instead, good cognitive functioning and having less depressive symptoms were prerequisites for participating in collective social activity among men and women. Among men, good cognitive functioning, and among women, good cognitive functioning and having less depressive symptoms were prerequisites for productive social activity. The health-enhancing influences of social activity may be partly explained by better mobility among persons who are socially active. Moreover, social activity may maintain mobility and thus decreases mortality risk, as many social activities also include physical activity. Better cognitive functioning and having less depressive symptoms should be considered as prerequisites for participating in social activities.