Colonization history of the Swiss Rhine basin by the bullhead (Cottus gobio): inference under a Bayesian spatially explicit framework

The present distribution of freshwater fish in the Alpine region has been strongly affected by colonization events occurring after the last glacial maximum (LGM), some 20,000 years ago. We use here a spatially explicit simulation framework to model and better understand their colonization dynamics in the Swiss Rhine basin. This approach is applied to the European bullhead (Cottus gobio), which is an ideal model organism to study fish past demographic processes since it has not been managed by humans. The molecular diversity of eight sampled populations is simulated and compared to observed data at six microsatellite loci under an approximate Bayesian computation framework to estimate the parameters of the colonization process. Our demographic estimates fit well with current knowledge about the biology of this species, but they suggest that the Swiss Rhine basin was colonized very recently, after the Younger Dryas some 6600 years ago. We discuss the implication of this result, as well as the strengths and limits of the spatially explicit approach coupled to the approximate Bayesian computation framework.

The complement inhibitor low molecular weight dextran sulfate prevents TLR4-induced phenotypic and functional maturation of human dendritic cells

Low molecular weight dextran sulfate (DXS) has been reported to inhibit the classical, alternative pathway as well as the mannan-binding lectin pathway of the complement system. Furthermore, it acts as an endothelial cell protectant inhibiting complement-mediated endothelial cell damage. Endothelial cells are covered with a layer of heparan sulfate (HS), which is rapidly released under conditions of inflammation and tissue injury. Soluble HS induces maturation of dendritic cells (DC) via TLR4. In this study, we show the inhibitory effect of DXS on human DC maturation. DXS significantly prevents phenotypic maturation of monocyte-derived DC and peripheral myeloid DC by inhibiting the up-regulation of CD40, CD80, CD83, CD86, ICAM-1, and HLA-DR and down-regulates DC-SIGN in response to HS or exogenous TLR ligands. DXS also inhibits the functional maturation of DC as demonstrated by reduced T cell proliferation, and strongly impairs secretion of the proinflammatory mediators IL-1beta, IL-6, IL-12p70, and TNF-alpha. Exposure to DXS leads to a reduced production of the complement component C1q and a decreased phagocytic activity, whereas C3 secretion is increased. Moreover, DXS was found to inhibit phosphorylation of IkappaB-alpha and activation of NF-kappaB. These findings suggest that DXS prevents TLR-induced maturation of human DC and may therefore be a useful reagent to impede the link between innate and adaptive immunity.

Functional and anatomical outcomes of vitreoretinal surgery for posterior segment complications after elective cataract surgery

PURPOSE: To assess the outcomes in patients who required 1 or more vitreoretinal interventions for posterior segment complications arising from elective uneventful cataract surgery. SETTING: Tertiary referral center, single-center study. METHODS: A retrospective interventional case series included 56 consecutive patients who were referred for surgical correction of posterior segment complications within 6 months of cataract surgery. The study period was between 1996 and 2003, and the minimum follow-up was 5 months. RESULTS: Posterior segment complications were resolved with a single surgical intervention in 40 cases (71.4%). Within 5 months of primary surgical correction, persisting or newly arising posterior segment complications were noted in 16 cases (28.6%). After a mean of 2.1 +/- 1.4 (SD) additional surgeries, the number of eyes with posterior segment problems decreased to 7 (12.5%) (P = .035). Posterior segment complications requiring more than 1 vitreoretinal intervention included retinal detachment, endophthalmitis, and choroidal hemorrhages. After primary correction surgery, the mean best corrected visual acuity increased from 0.15 +/- 0.24 to 0.37 +/- 0.33 (P = .001) after a single intervention and to 0.39 +/- 0.32 (P>.05) after additional interventions. Although the intraocular pressure (IOP) decreased from 21.8 +/- 16.6 mm Hg to 14.9 +/- 3.4 mm Hg (P = .008), 4 (7.1%) consecutive vascular optic atrophies occurred. A reduction in corneal transparency was observed in 46.4% of patients before primary surgical correction and 12.5% after primary surgical correction (P<.001). CONCLUSIONS: In many cases, posterior segment complications arising from cataract surgery could be repaired with favorable functional and anatomical outcomes by a single vitreoretinal intervention. Additional surgery, if requested, provided stabilization of the anatomical and functional outcomes.

Value of a novel Neisseria meningitidis--specific polymerase chain reaction assay in skin biopsy specimens as a diagnostic tool in chronic meningococcemia

BACKGROUND: Chronic meningococcemia (CM) is a diagnostic challenge. Skin lesions are frequent but in most cases nonspecific. Polymerase chain reaction (PCR)-based diagnosis has been validated in blood and cerebrospinal fluid for acute Neisseria meningitidis infection, in patients in whom routine microbiologic tests have failed to isolate the bacteria. In 2 patients with CM, we established the diagnosis by a newly developed PCR-based approach performed on skin biopsy specimens. OBSERVATIONS: Two patients presented with fever together with systemic and cutaneous manifestations suggestive of CM. Although findings from blood cultures remained negative, we were able to identify N meningitidis in the skin lesions by a newly developed PCR assay. In 1 patient, an N meningitidis strain of the same serogroup was also isolated from a throat swab specimen. Both patients rapidly improved after appropriate antibiotherapy. CONCLUSIONS: To our knowledge, we report the first cases of CM diagnosed by PCR testing on skin biopsy specimens. It is noteworthy that, although N meningitidis-specific PCR is highly sensitive in blood and cerebrospinal fluid in acute infections, our observations underscore the usefulness of PCR performed on skin lesions for the diagnosis of chronic N meningitidis infections. Whenever possible, this approach should be systematically employed in patients for whom N meningitidis infection cannot be confirmed by routine microbiologic investigations.

Treatment of mediastinal fibrosis with mycophenolate mofetil

We present the case of a 67-year-old male patient with mediastinal and retroperitoneal fibrosis. In Europe, this is a rare disease. Treatment was established to prevent complications due to strictures or compressions. Because of his diabetes, a therapy of low-dose prednisone combined with mycophenolate mofetil, known as steroid sparing agent, was applied. As a result, the radiological follow-up showed a marked decrease in the mediastinal and retroperitoneal masses.

Gender differences in patients referred for atrial fibrillation management to a tertiary center

BACKGROUND: Atrial fibrillation (AF) ablation is less frequently performed in women than in men. Although the prevalence of AF is slightly higher in men, this does not fully account for the lower number of AF ablations performed in women. This study sought to examine the effect of gender on referral for AF and subsequent AF management. METHODS: Consecutive patients referred to our tertiary arrhythmia outpatient clinic for AF management were retrospectively analyzed. RESULTS: Of 264 patients referred, only 27% were women. Women were older than men (63 +/- 9 vs 58 +/- 11 years, P = 0.002), more often had paroxysmal AF (78% vs 63% in men, P = 0.022), and women more frequently complained about palpitations (71% vs 49%, P = 0.002). In addition, they had more often experienced amiodarone side effects than men (56% vs 36%, P = 0.046). In this referred population, there was no difference in the proportion of women and men undergoing AF ablation immediately following the initial evaluation (21% vs 25%, P = ns), at any time during the follow-up (38% vs 44%, P = ns), and there was no difference in the proportion of patients undergoing atrioventricular node ablation in both sexes (6% of women vs 3% of men, P = ns). CONCLUSIONS: There is an important difference in the proportion of men and women referred for management of AF in a specialized outpatient arrhythmia clinic, with women being referred three times less often than men. However, there is no gender-related difference in the subsequent treatment decisions. These findings emphasize the importance of focusing on management of symptomatic AF in women.

Diastolic dysfunction of the cardiac allograft and maximal exercise capacity

BACKGROUND: Peak oxygen uptake (peak Vo(2)) is an established integrative measurement of maximal exercise capacity in cardiovascular disease. After heart transplantation (HTx) peak Vo(2) remains reduced despite normal systolic left ventricular function, which highlights the relevance of diastolic function. In this study we aim to characterize the predictive significance of cardiac allograft diastolic function for peak Vo(2). METHODS: Peak Vo(2) was measured using a ramp protocol on a bicycle ergometer. Left ventricular (LV) diastolic function was assessed with tissue Doppler imaging sizing the velocity of the early (Ea) and late (Aa) apical movement of the mitral annulus, and conventional Doppler measuring early (E) and late (A) diastolic transmitral flow propagation. Correlation coefficients were calculated and linear regression models fitted. RESULTS: The post-transplant time interval of the 39 HTxs ranged from 0.4 to 20.1 years. The mean age of the recipients was 55 +/- 14 years and body mass index (BMI) was 25.4 +/- 3.9 kg/m(2). Mean LV ejection fraction was 62 +/- 4%, mean LV mass index 108 +/- 22 g/m(2) and mean peak Vo(2) 20.1 +/- 6.3 ml/kg/min. Peak Vo(2) was reduced in patients with more severe diastolic dysfunction (pseudonormal or restrictive transmitral inflow pattern), or when E/Ea was > or =10. Peak Vo(2) correlated with recipient age (r = -0.643, p < 0.001), peak heart rate (r = 0.616, p < 0.001) and BMI (r = -0.417, p = 0.008). Of all echocardiographic measurements, Ea (r = 0.561, p < 0.001) and Ea/Aa (r = 0.495, p = 0.002) correlated best. Multivariate analysis identified age, heart rate, BMI and Ea/Aa as independent predictors of peak Vo(2). CONCLUSIONS: Diastolic dysfunction is relevant for the limitation of maximal exercise capacity after HTx.