Why Our Next President May Keep His or her Senate Seat: A Conjecture on the Constitution’s Incompatibility Clause

Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention

Pacemaker implantation in small hospitals: complication rates comparable to larger centres

Some countries have a demography that makes it necessary to maintain relatively small pacemaker centres. We wanted to assess the quality of pacemaker surgery in two such hospitals. Through patient records we gathered information on ∼535 consecutive primary pacemaker implantations in two small pacemaker centres with 30 and 80 annual operations, respectively. All patients were followed for 3 years. All complications documented in the patient records were registered. Furthermore, we performed a non-systematic literature search comparing our data with reports from major centres published over the last 10 years.We found 72 complications in 64 (12.0%) of the patients, the most common being bleeding, lead failure, and pneumothorax. If minor bleedings without any consequences for the patients are excluded, the number of complications was 46 in 40 patients (7.5%). We had to reoperate on 5.2% of the patients. There was no statistically significant difference in complication rates between the two hospitals. Education candidates generated statistically significant more complications than experienced doctors (13.7 vs. 7.1%, P < 0.05). There are no generally accepted norms of complication rates in pacemaker surgery. However, we found no indications that our centres have a rate of complications that is unacceptably high

Declining trends in conception rates in recent birth cohorts of native Danish women: a possible role of deteriorating male reproductive health

Recent findings of poor semen quality among at least 20% of normal young men in Denmark prompted us to use unique Danish registers on births and induced abortions to evaluate a possible effect of the poor male fecundity on pregnancy rates among their presumed partners – the younger cohorts of women. We have analysed data from the Danish birth and abortion registries as well as the Danish registry for assisted reproduction (ART) and defined a total natural conception rate (TNCR), which is equal to fertility rate plus induced abortion rate minus ART conception rate. A unique personal identification number allowed the linkage of these databases. Our database included 706 270 native Danish women born between 1960 and 1980. We used projections to estimate the fertility of the later cohorts of women who had not yet finished their reproduction. We found that younger cohorts had progressively lower TNCR and that in terms of their total fertility rate, the declining TNCR is compensated by an increasing use of ART. Our hypothesis of an ongoing birth cohort-related decline in fecundity was also supported by our finding of increasing and substantial use of ART in the management of infertility of relatively young couples in the later cohorts. Furthermore, the lower rates of induced abortion among the younger birth cohorts, often viewed as a success of health education programs, may not be fully explained by improved use of contraception. It seems more likely that decreased fecundity because of widespread poor semen quality among younger cohorts of otherwise normal men may explain some of the observed decline in conception rates. This may imply increasing reproductive health problems and lower fertility in the future, which is difficult to reverse in the short term. The current and projected widespread use of ART in Denmark may be a sign of such an emerging public health problem

Functional Analysis of Ficolin-3 Mediated Complement Activation

The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway

Persistent Hepatitis B Viral Replication in a FVB/N Mouse Model: Impact of Host and Viral Factors

The mechanism underlying the chronicity of hepatitis B virus (HBV) infection has long been an interesting question. However, this mechanism remains unclear largely due to the lack of an animal model that can support persistent HBV replication and allow for the investigation of the relevant immune responses. In this study, we used hydrodynamic injection to introduce HBV replicon DNA into the livers of three different mouse strains: BALB/c, C57BL/6, and FVB/N. Interestingly, we found that an HBV clone persistently replicated in the livers of FVB/N mice for up to 50 weeks but was rapidly cleared from the livers of BALB/c and C57BL/6 mice. Flow cytometric analysis and quantitative reverse transcription PCR analysis of the mouse livers indicated that after DNA injection, FVB/N mice had few intrahepatic activated cytotoxic T lymphocytes (CTLs) and produced low levels of alanine aminotransferase, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and the CXCL9 and CXCL10 chemokines. These findings were in sharp contrast with those observed in BALB/c and C57BL/6 mice, reflecting a strong correlation between the degree of liver inflammation and viral clearance. Mutational analysis further demonstrated that a change of Asn-214 to Ser-214 in the HBV surface antigen rendered the persistent HBV clone clearable in FVB/N mice, which was accompanied by increased levels of activated CTL and upregulated expression of IFN-γ, CXCL9, and CXCL10 in the livers. These results indicate that the heterogeneity of the host factors and viral sequences may influence the immune responses against HBV. An inadequate activation of immune or inflammatory responses can lead to persistent HBV replication in vivo

Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis

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