G-quadruplexes (G4) are stacked nucleic acid structures that are stabilized by heme. In cells, they affect DNA replication and gene transcription. They are unwound by several helicases but the ...composition of the repair complex and its heme sensitivity are unclear. We found that the accumulation of G-quadruplexes is affected by heme oxygenase-1 (
) expression, but in a cell-type-specific manner: hematopoietic stem cells (HSCs) from
mice have upregulated expressions of G4-unwinding helicases (e.g.,
,
) and show weaker staining for G-quadruplexes, whereas
-deficient murine induced pluripotent stem cells (iPSCs), despite the upregulation of helicases, have more G-quadruplexes, especially after exposure to exogenous heme. Using iPSCs expressing only nuclear or only cytoplasmic forms of Hmox1, we found that nuclear localization promotes G4 removal. We demonstrated that the proximity ligation assay (PLA) can detect cellular co-localization of G-quadruplexes with helicases, as well as with HMOX1, suggesting the potential role of HMOX1 in G4 modifications. However, this colocalization does not mean a direct interaction was detectable using the immunoprecipitation assay. Therefore, we concluded that HMOX1 influences G4 accumulation, but rather as one of the proteins regulating the heme availability, not as a rate-limiting factor. It is noteworthy that cellular G4-protein colocalizations can be quantitatively analyzed using PLA, even in rare cells.
Pulmonary arterial hypertension (PAH) leads to a haemodynamic overload and ischaemia of the right ventricle (RV), which are important triggers of an arterial growth. Thus, we aimed to assess whether ...patients with PAH have altered epicardial vasculature of the RV, and how it corresponds to RV haemodynamic stress.
We enrolled consecutive patients with PAH diagnosed in a single pulmonary hypertension centre, who underwent coronary angiography. The control group consisted of patients with normal coronary arteries. Artery branches from segments I–III of the right coronary artery (RCAB) and branches of the left coronary artery (LCAB) were assessed. The sum of the diameters of RCABs (RCAB_sum) was used as a marker of RV epicardial vascularisation. Linear regression models were used to investigate associations between the RCAB_sum and markers of RV dysfunction.
We recruited 37 PAH patients (idiopathic, n=25; associated with connective tissue disease, n=12) and 37 control subjects of similar age (56±18 vs. 56±13 years, p=0.99) and sex (73% vs. 73% of women, p=0.99). Pulmonary arterial hypertension patients as compared with control subjects had more RCABs (7 6–8 vs. 6 5–7, p<0.001) and increased RCAB_sum (9.4 8.2–10.5 vs. 7.3 6.6–7.40 mm; p<0.001) although comparable LCAB count (4 4–5 vs. 4 4–5; p=0.50). In a stepwise multivariable linear regression model, RA area (β=0.152 0.062–0.242; p=0.002) and diastolic wall stress (β=0.025 0.005–0.045; p=0.02) were significant predictors of RCAB_sum (model R2=0.65; p<0.0001).
Right ventricular epicardial vasculature is more extensive in PAH patients as compared with control subjects, and it is in linear relation to potential markers of RV diastolic dysfunction.
INTRODUCTION Rare cardiovascular diseases and disorders (RCDDs) constitute an important clinical problem, and their proper classification is crucial for expanding knowledge in the field of RCDDs. ...OBJECTIVES The aim of this paper is to provide an updated classification of rare arrhythmogenic and conduction disorders, and rare arrhythmias (RACDRAs). METHODS We performed a search for RACDRAs using the Orphanet inventory of rare diseases, which includes diseases with a prevalence of no more than 5 per 10 000 in the general population. We supplemented this with a search of PubMed and Scopus databases according to a wider definition proposed by the European Parliament and the Council of the European Union. RESULTS RACDRAs are categorized into 2 groups, primary electrical disorders of the heart and arrhythmias in specific clinical settings. The first group is further divided into subgroups of major clinical presentation: disorders predisposing to supraventricular tachyarrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and others. The second group includes iatrogenic arrhythmias or heart rhythm disturbances related to medical treatment, arrhythmias associated with metabolic disorders, and others. We provide a classification of RACDRAs and supplement them with respective RCDDs codes. CONCLUSION The clinical classification of RACDRAs may form a basis to facilitate research and progress in clinical practice, both in diagnostic and therapeutic approaches.
Background:
Significant achievements in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) have provided effective therapeutic options for most patients. However, the true impact ...of the changed landscape of CTEPH therapies on patients’ management and outcomes is poorly known. We aimed to characterize the incidence, clinical characteristics, and outcomes of CTEPH patients in the modern era of CTEPH therapies.
Methods:
We analyzed the data of CTEPH adults enrolled in the prospective multicenter registry.
Results:
We enrolled 516 patients aged 63.8 ± 15.4 years. The incidence rate of CTEPH was 3.96 per million adults per year. The group was burdened with several comorbidities. New oral anticoagulants (n = 301; 58.3%) were preferred over vitamin K antagonists (n = 159; 30.8%). Pulmonary endarterectomy (PEA) was performed in 120 (23.3%) patients and balloon pulmonary angioplasty (BPA) in 258 (50%) patients. PEA was pretreated with targeted pharmacotherapy in 19 (15.8%) patients, and BPA in 124 (48.1%) patients. Persistent CTEPH was present in 46% of PEA patients and in 65% of patients after completion of BPA. Persistent CTEPH after PEA was treated with targeted pharmacotherapy in 72% and with BPA in 27.7% of patients. At a mean time period of 14.3 ± 5.8 months, 26 patients had died. The use of PEA or BPA was associated with better survival than the use of solely medical treatment.
Conclusions:
The modern population of CTEPH patients comprises mostly elderly people significantly burdened with comorbid conditions. This calls for treatment decisions that are tailored individually for every patient. The combination of two or three methods is currently a frequent approach in the treatment of CTEPH.
Clinical Trial Registration:
clinicaltrials.gov/ct2/show/NCT03959748
•Birds may avoid recapture for some time after they have been captured.•Period between capture-recapture of Great Tits was depended from their sex and age.•Size of the human settlements did not ...affect time to recapture of tits.
Urban and rural habitats provide different conditions to wintering birds mainly due to different access to bird feeders. Returning to the food sources, even under the stress related to trapping, could play an important role in the energetic budget of wintering birds. We studied the duration of period between the first and the second capture of the Great Tits (Parus major) caught and ringed at bird feeders. We expected that recapturing of birds, which could be connected with their experience, would depend on their sex, age and on the size of human settlements (urban vs. rural areas), which could modify the behavior of wintering birds. We found that the length of the period was the shortest for immature females and the longest for adult males (the difference being 3.8 days in average). In contrast to more experienced adults, more frequent visits in case of immature tits, which increased probability of being trapped, could be affected by their weaker condition and smaller size, which resulted in feeding whenever it was possible. At the same time we did not find any differences between urban (duration of 29.5 days in average) and rural (28.5 days) areas. Differentiation in bird densities, access to feeders and various environmental factors seems to be the reason why this issue awaits further, more detailed studies including influence of weather on the behavior of birds.
Winter is one of the crucial periods of the bird’s year-round life cycle. Fat reserves in bird species are prone to a wide range of factors, with weather conditions and a bird’s social status being ...two major ones. In our study we analysed the variation in fat reserves in birds with stable, constant access to food resources in three of the most common wintering species: the great tit Parus major, the blue tit Cyanistes caeruleus and the greenfinch Chloris chloris. The highest mean value of fat score was found in the greenfinch, whereas in both species of tits these values were equally lower. For all three species the amount of fat reserve was correlated with the same factors. It increased together with the decrease of mean average temperature, and with the course of daytime as well as the season-site index (calculated as data collected at a given site in a particular year). Contrary to many previous surveys we did not find dependence of the fat score level on individual dominance status, which is probably linked to the abundance of food in catching sites.
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