Old and new cardiovascular risk factors: from unresolved issues to new opportunities

With the aim of identifying areas that may deserve some further thinking the present review deliberately points out controversial issues in cardiovascular research and risk assessment. In the first part of the review general aspects are addressed regarding the evaluation of risk factors. A first point of concern is the frequent practice of combining different vascular events and effects in different vascular beds into a single endpoint. Furthermore, verification of vascular events in clinical reality may be surprisingly inaccurate. Problems in risk assessment also arise from overlapping properties (shared pathophysiological pathways) of traditional risk factors like hypertension, obesity and diabetes. In the second part of the review unresolved issues concerning selected established and emerging risk factors are discussed. The difficulty of establishing causality in cardiovascular disease is addressed, using modification of LDL cholesterol and accumulating evidence for pleiotropic effects of the LDL cholesterol-lowering statins as an example. As an alternative or supplement to the notion of LDL-related cardiovascular risk it is proposed to distinguish between statin-sensitive and statin-insensitive cardiovascular risk. Finally the future prospects of selected new and emerging risk factors like CRP, homocysteine, asymmetrical dimethylarginine (ADMA), oxLDL, and isoprostanes are evaluated. In summary, imprecise terminology and varying definitions of "cardiovascular risk" may lead to a considerable blurring of our current risk estimates, which may also explain some presently controversial issues. With several new risk factors and substantial changes in lifestyle and treatment patterns on the horizon major changes in the hierarchy of risk factors may be inevitable.     

Molecular background of Rh D-positive,D-negative,D(el) and weak D phenotypes in Chinese

BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the genetic background of D-negative and D(el) in the Chinese population. MATERIALS AND METHODS: We investigated nine D-positive, 76 D-negative, 26 D(el) and three weak D Chinese individuals by amplification and sequencing of the complete coding region of the RHD gene from genomic DNA. A new RHD polymerase chain reaction with sequence-specific primers (PCR-SSP) method was developed with optimized specificity for typing Chinese individuals. RESULTS: In D-positive samples the RHD sequence was in complete concordance with RHD in other populations. In 12 of 76 (15.8%) D-negative individuals we detected regions of RHD. Three new alleles were found. All 26 D(el), as well as two weak D, individuals carried an RHD 1227A allele. In the remaining weak D sample we identified a weak D type 15. CONCLUSIONS: It should now be possible to correctly predict the RhD phenotype in Chinese subjects. D(el) can also be designated as a particular weak D type.     

A word of hope for ataxia trials in COVID-19 time and beyond

Journal of Neurology - The coronavirus disease 2019 (COVID-19) crisis confronted us, like many researchers worldwide, with an unforeseen challenge during the final stages of a randomized controlled...     

Submaximal arm crank ergometry: Effects of crank axis positioning on mechanical efficiency,physiological strain and perceived discomfort

Purpose: To evaluate the effect of the spatial orientation of the crank axis on mechanical efficiency, physiological strain and perceived discomfort in submaximal synchronous arm crank ergometry.

Methods: Twelve able-bodied individuals performed 12 submaximal exercise bouts of 3 minutes (women: 20 W/25 W; men: 25 W/35 W). The crank axis position was defined by elbow and shoulder angle.

Results: The results showed that a crank set-up with an elbow angle of 30° was more efficient than 15°; oxygen consumption and minute ventilation were significantly lower. No significant effects were seen for shoulder angle. Power output and gender showed obvious effects.

Discussion and conclusion: The magnitude of this effect and the absence of any significant shoulder angle effects may be due to the relative low exertion levels that were evaluated. An elbow angle of 30° flexion in arm crank exercise is favourable compared to an elbow angle of 15° in able-bodied untrained subjects.     

Sensitive methods for determining subclasses of IgG anti-A and anti-B in sera of blood-group-O women with a blood-group-A or -B child

The determination of the subclasses of IgG antibodies against blood groups A and B is important in order to improve our understanding and predict haemolytic disease of the newborn due to IgG anti-A or -B. We describe two techniques that circumvent the problem of the agglutination of A and B red cells by the corresponding IgG antibodies in saline: an antiglobulin consumption test and a modified solid-phase micro-immunofluorescence test. The results of the two techniques are compared with the results obtained in the indirect antiglobulin test beyond the saline agglutination titre in a microplate technique. The solid-phase micro-immunofluorescence test was the most sensitive for the determination of the subclasses of IgG anti-A and -B. Usually sera contained IgG2 anti-A, B in a higher titre than antibodies of other subclasses.     

Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice

The normal skin and other tissues of adult mast cell-deficient WBB6F1- W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. As a result, genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice are widely used for studies of mast cell differentiation and function. We found that mast cells developed at sites of idiopathic chronic dermatitis in WBB6F1-W/Wv mice and that the number of mast cells present in the skin of WBB6F1-W/Wv mice was proportional to the severity of the dermatitis (in ear skin, there were 33 +/- 4 mast cells/mm2 of dermis at sites of severe dermatitis v 9 +/- 3 at sites of mild dermatitis, 0.8 +/- 0.3 in skin without dermatitis, and 100 +/- 7 in the normal skin of congenic WBB6F1-+/+ mice; in back skin, the corresponding values were 2.0 +/- 0.6, 1.1 +/- 0.9, 0.025 +/- 0.025, and 26.2 +/- 3.2). The development of mast cells was a local, not systemic, consequence of the dermatitis. Thus, WBB6F1-W/Wv mice with severe dermatitis lacked mast cells in skin not showing signs of dermatitis and also in the peritoneal cavity, stomach, cecum, and tongue. Idiopathic chronic dermatitis was not associated with the local development of mast cells in WCB6F1-Sl/Sld mice, a mutant whose mast cell deficiency is due to a mechanism distinct from that of WBB6F1-W/Wv mice. These findings may have implications for understanding the nature of the mast cell deficiency in WBB6F1-W/Wv and WCB6F1-Sl/Sld mice and for the use of these mutants to analyze mast cell differentiation and function.