Diagnosis of takotsubo cardiomyopathy is increasing over time in patients presenting as ST-elevation myocardial infarction

Background

Takotsubo cardiomyopathy often presents with the clinical signs of ST-elevation myocardial infarction (STEMI). The increase in scientific publications addressing this relatively rare condition may result in higher awareness and diagnosis of takotsubo cardiomyopathy.

Aim

To assess the observed prevalence per year of takotsubo cardiomyopathy in a large registry of patients with STEMI, during a 12-year inclusion period.

Method

All patients presenting with STEMI at a large regional cardiology clinic were entered into a database (n = 8,413, mean age 63 ± 13 years). Takotsubo cardiomyopathy was diagnosed in 42 patients (0.5?%). Years of evaluation were defined as ‘early years’ (January 2002 to December 2007; n = 4350) and ‘later years’ (January 2008 to December 2013). Multivariable analyses were performed to adjust for differences in demographical and clinical variables.

Results

In later years, the age of STEMI patients was slightly higher (64 ± 13 vs. 63 ± 13 years, p < 0.001), with more patients with clinical symptoms of shock (10 vs. 7?%, p < 0.001) or a history of percutaneous coronary intervention or hypertension (10 vs. 8?%, p = 0.001 and 37 vs. 34?%, p < 0.001). Smoking and a positive family history were less often observed during later years (39 vs. 46?%, p < 0.001 and 37 vs. 42?% p < 0.001). Patients with takotsubo cardiomyopathy were more often female (81 vs. 27?%, p = 0.001). Takotsubo cardiomyopathy was more often diagnosed in the later period (0.7 vs. 0.3?%, OR 2.4, 95?% CI 1.2–4.6, p = 0.009). The higher prevalence of takotsubo cardiomyopathy in recent years remained significant after adjustment for differences in patient characteristics (OR 2.1, 95?% CI 1.1–4.3).

Conclusion

Takotsubo cardiomyopathy is currently more often diagnosed in patients with STEMI compared with in earlier years. This is probably due to the increased scientific and clinical awareness among doctors, but the prevalence is still low.

     

Phylogenetic diversification of immunoglobulin genes and the antibody repertoire

Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function.      

An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains

To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation.     

Isolation and characterization of novel bacterial strains exhibiting ligninolytic potential

Background

The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD⁺ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD⁺. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds.

Results

The NADH-oxidase (NOX) presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80°C) under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37°C). The hyperactivated form presented a high specific activity (37.5 U/mg) at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme). The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols.

Conclusion

We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations.     

A randomised,investigator-initiated,clinical trial of the effects of fentanyl on P2Y12-receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: rationale and design of the Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial

Background

Fast and accurate platelet inhibition is an important therapeutic goal in the acute treatment of patients with ST-elevation myocardial infarction (STEMI). Platelet inhibitory effects induced by oral P2Y12-receptor antagonists are delayed in STEMI patients undergoing primary percutaneous coronary intervention (PCI) due to haemodynamic changes and delayed gastro-intestinal absorption. Concomitant use of opioids, although recommended in the American College of Cardiology/American Heart Association and European Society of Cardiology STEMI guidelines, further delays gastro-intestinal absorption. To date, trials investigating alternative analgesics in STEMI patients have been scarce. This trial aims to assess the feasibility of a novel drug strategy for treatment of STEMI patients with crushed ticagrelor in combination with paracetamol (acetaminophen) instead of opioids.

Hypothesis

STEMI patients who are pre-treated with crushed ticagrelor and paracetamol have a higher level of platelet inhibition after primary PCI than patients pre-treated with crushed ticagrelor and fentanyl.

Study design

The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial is a randomised controlled trial designed to examine whether administration of paracetamol instead of fentanyl can optimise platelet inhibition in STEMI patients who are pre-treated with crushed ticagrelor in the ambulance. One hundred and ninety patients with STEMI will be randomised (1:1 fashion) to intravenous (IV) fentanyl or IV paracetamol. The primary endpoint is the level of platelet reactivity units measured immediately after primary PCI.

Summary

The ON-TIME 3 trial (NCT03400267) aims to achieve optimal platelet inhibition and pain relief in STEMI patients receiving crushed ticagrelor in the ambulance by investigating IV fentanyl and IV paracetamol as analgesics.

     

Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants

Background  

Toxoplasma gondii is a zoonotic parasite of global importance. In common with many protozoan parasites it has the capacity for sexual recombination, but current evidence suggests this is rarely employed. The global population structure is dominated by a small number of clonal genotypes, which exhibit biallelic variation and limited intralineage divergence. Little is known of the genotypes present in Africa despite the importance of AIDS-associated toxoplasmosis.