Structural right ventricular (RV) abnormalities are present in a substantial proportion of patients with hypertrophic cardiomyopathy (HCM), but the trigger for RV hypertrophy remains unclear. The aim ...of this study was to assess the relationship between RV and left ventricular (LV) remodeling and the impact of biventricular involvement on clinical status in this setting.
Ninety-nine patients with HCM and 30 normal subjects with a similar age and gender distribution were prospectively enrolled. Comprehensive echocardiography was performed in all, including the assessment of LV and RV function by tissue Doppler and speckle-tracking echocardiography. Measurement of RV free wall thickness (RVWT) was performed at end-diastole, in a zoomed subcostal view, focusing on the RV midwall.
Patients with HCM had increased RVWT (6.4 ± 1.9 vs 3.6 ± 0.8 mm, P < .001) and lower values of RV global longitudinal strain (-19.4 ± 4.4% vs -23.8 ± 2.7%, P < .001) compared with control subjects. RVWT was independently related to LV mass and LV global longitudinal strain. Increased RVWT was correlated with New York Heart Association class (r = 0.20, P = .04) and calculated sudden cardiac death risk score (r = 0.52, P < .001) and was independently related to the presence of ventricular arrhythmias (odds ratio, 2.02; 95% CI, 1.28-3.19; P = .002).
In patients with HCM, the presence of RV hypertrophy was associated with increased LV mass and reduced LV longitudinal strain, correlated with increased calculated sudden cardiac death risk score, and independently related to the presence of ventricular arrhythmias. These data suggest more severe disease in patients with biventricular HCM.
Obstructive sleep apnea (OSA) can lead to cardiac complications: brady and tachyarrhythmias and sudden cardiac death. Continuous positive airway pressure (CPAP) is the gold standard for the treatment ...of OSA. The present study aims to demonstrate the efficiency of CPAP in the treatment of cardiac arrhythmias in patients with OSA. The study also recorded the frequency of arrhythmias in patients with untreated OSA and assessed the association between the severity of OSA and the occurrence of arrhythmias.
This is a prospective cohort study. Ninety-three patients with OSA were included, aged 60 (58-64) years, with female/male sex ratio of 1:4. They were subjected simultaneously to home respiratory polygraphy examination and Holter electrocardiogram monitoring, in two different stages: at diagnosis and at the 3-month checkup after CPAP treatment. The presence of supraventricular and ventricular arrythmias was noted. Respiratory parameter values were also recorded.
Statistically significant decrease in the occurrence of supraventricular (
< 0.001) and ventricular extrasystoles (
< 0.001), atrial fibrillation (AF) (
= 0.03), nonsustained ventricular tachycardia (NSVT) (
= 0.03), and sinus pauses (
< 0.001) was observed 3 months after treatment with CPAP, compared with baseline. The apnea-hypopnea index (AHI) was correlated with the ventricular extrasystoles (
= 0.273;
= 0.008). The ejection fraction of the left ventricle was inversely correlated with the episodes of NSVT (
= -0.425;
< 0.001). AF was associated with the longest apnea (
= 0.215;
= 0.04). Cardiac activity pauses were correlated with AHI (
= 0.320;
= 0.002), longest apnea (
= 0.345;
= 0.01), and oxygen desaturation index (
= 0.325;
= 0.04).
The prevalence of cardiac arrhythmias in patients with OSA was reduced after 3 months of CPAP therapy. Cardiac arrhythmias were correlated with the severity of OSA.
Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor ...(P2Y12R) has been implicated in CB; however, the exact role of the receptor in O
sensing and signal transduction is unknown.
The presence of P2Y12R was established by immunoblotting, RT qPCR and immunohistochemistry. Primary glomus cells were used to assess P2Y12R function during hypoxia and hypercapnia, where monoamines were measured by HPLC; calcium signal was recorded utilizing OGB-1 and N-STORM Super-Resolution System. Ingravescent hypoxia model was tested in anaesthetized mice of mixed gender and cardiorespiratory parameters were recorded in control and receptor-deficient or drug-treated experimental animals.
Initially, the expression of P2Y12R in adult murine CB was confirmed. Hypoxia induced a P2Y12R-dependent release of monoamine transmitters from isolated CB cells. Receptor activation with the endogenous ligand ADP promoted release of neurotransmitters under normoxic conditions, while blockade disrupted the amplitude and duration of the intracellular calcium concentration. In anaesthetised mice, blockade of P2Y12R expressed in the CB abrogated the initiation of compensatory cardiorespiratory changes in hypoxic environment, while centrally inhibited receptors (i.e. microglial receptors) or receptor-deficiency induced by platelet depletion had limited influence on the physiological adjustment to hypoxia.
Peripheral P2Y12R inhibition interfere with the complex mechanisms of acute oxygen sensing by influencing the calcium signalling and the release of neurotransmitter molecules to evoke compensatory response to hypoxia. Prospectively, the irreversible blockade of glomic receptors by anti-platelet drugs targeting P2Y12Rs, propose a potential, formerly unrecognized side-effect to anti-platelet medications in patients with pulmonary morbidities.
In vivo studies in humans and mice have implicated the pseudokinase Tribbles 3 (TRIB3) in various aspects of energy metabolism. Whilst cell-based studies indicate a role for TRIB3 in adipocyte ...differentiation and function, it is unclear if and how these cellular functions may contribute to overall metabolic health.
We investigated the metabolic phenotype of whole-body Trib3 knockout (Trib3
) mice, focusing on adipocyte and adipose tissue functions. In addition, we combined lipidomics, transcriptomics, interactomics and phosphoproteomics analyses to elucidate cell-intrinsic functions of TRIB3 in pre- and mature adipocytes.
Trib3
mice display increased adiposity, but their insulin sensitivity remains unaltered. Trib3
adipocytes are smaller and display higher Proliferating Cell Nuclear Antigen (PCNA) levels, indicating potential alterations in either i) proliferation-differentiation balance, ii) impaired expansion after cell division, or iii) an altered balance between lipid storage and release, or a combination thereof. Lipidome analyses suggest TRIB3 involvement in the latter two processes, as triglyceride storage is reduced and membrane composition, which can restrain cellular expansion, is altered. Integrated interactome, phosphoproteome and transcriptome analyses support a role for TRIB3 in all three cellular processes through multiple cellular pathways, including Mitogen Activated Protein Kinase- (MAPK/ERK), Protein Kinase A (PKA)-mediated signaling and Transcription Factor 7 like 2 (TCF7L2) and Beta Catenin-mediated gene expression.
Our findings support TRIB3 playing multiple distinct regulatory roles in the cytoplasm, nucleus and mitochondria, ultimately controlling adipose tissue homeostasis, rather than affecting a single cellular pathway.
Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis ...and management of HAE provides up‐to‐date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on‐demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast‐feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.
Aquatic non-targeted organisms are more likely to be exposed to herbicides in multiple pulse events then long continuous exposure. The potential of an organism to recover between exposures has an ...important role in the overall effects of the toxicant. Common duckweeds show high potential for recovery after a single exposure to isoproturon. To evaluate the growth patterns and recovery potential between multiple exposures,
L. minor
plants were exposed to isoproturon in three repetitive 7-day treatment cycles in three time-variable exposure scenarios with equivalent time-weighted average concentrations. The growth was significantly inhibited during each exposure phase with significant cumulative effects in every subsequent treatment cycle resulting in a cumulative decrease in biomass production. However, inhibitory effects were reversible upon transferring plants to a herbicide-free nutrient solution. These results indicate that
L. minor
plants have a high recovery potential even after multiple exposures to isoproturon. Observed cumulative decrease in biomass production, as well as the potential for fast and efficient recovery from repeated herbicide exposure, might affect the competitiveness of
L. minor
in surface water communities. The observations made during each exposure period, recovery patterns, and the resulting cumulative effects over time may contribute to further development, calibration and validation of mechanistic toxicokinetic/toxicodynamic models for simulating the effects of pesticides on aquatic plants populations in the laboratory and environmental conditions.
Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled ...gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice.
Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging.
Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.
Does chromatin function as a metabolite reservoir? Nirello, Vinícius D.; Rodrigues de Paula, Dieggo; Araújo, Nathália V.P. ...
Trends in biochemical sciences (Amsterdam. Regular ed.),
September 2022, 2022-09-00, 20220901, Letnik:
47, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Alternative histone acylations integrate gene expression with cellular metabolic states. Recent measurements of cellular acyl-coenzyme A (acyl-CoA) pools highlight the potential that histone ...post-translational modifications (PTMs) contribute directly to the regulation of metabolite pools. A metabolite-centric view throws new light onto roles and evolution of histone PTMs.
The range of hosts exploited by a parasite is determined by several factors, including host availability, infectivity and exploitability. Each of these can be the target of natural selection on both ...host and parasite, which will determine the local outcome of interactions, and potentially lead to coevolution. However, geographical variation in host use and specificity has rarely been investigated. Maculinea (= Phengaris) butterflies are brood parasites of Myrmica ants that are patchily distributed across the Palæarctic and have been studied extensively in Europe. Here, we review the published records of ant host use by the European Maculinea species, as well as providing new host ant records for more than 100 sites across Europe. This comprehensive survey demonstrates that while all but one of the Myrmica species found on Maculinea sites have been recorded as hosts, the most common is often disproportionately highly exploited. Host sharing and host switching are both relatively common, but there is evidence of specialization at many sites, which varies among Maculinea species. We show that most Maculinea display the features expected for coevolution to occur in a geographic mosaic, which has probably allowed these rare butterflies to persist in Europe. This article is part of the theme issue 'The coevolutionary biology of brood parasitism: from mechanism to pattern'.
Food waste is a problem for which solutions are recognised but not readily put into practice. What should be the primary objective, reducing or eliminating surplus food production, requires great ...change within social, cultural and economic structures. The secondary approach of redistributing surplus food to areas of deficit (in terms of socio-economic groups and/or geographic regions) involves a significant logistical burden, and suffers the same issues as with the elimination of waste. The least desirable, but perhaps most practicable approach, is the use of food waste as a feedstock for Anaerobic Digestion (AD). The strategic adoption of AD can therefore be seen as an important step towards mitigating food waste, but the implementation of efficient AD systems on a large (county/region) scale involves significant complexity. The optimal number, size and location of AD plants, and whether they are centralised versus decentralised, may be determined by considering factors such as supply and proximity to feedstock, transport links, emission hazards and social impact. Reaching balanced and objective decisions when faced with such disparate criteria is inevitably very difficult. To address this problem we prototype and evaluate a decision support tool for county-scale AD planning. Our approach is a hybridised Agent Based Model (ABM) with a Multi Objective Optimisation. We capture the spatio-temporal dependencies that exist in the water, energy and food systems associated with energy derived from food waste using Agent Based Modelling (ABM). The use of Interactive Multi Criteria Analysis as visual analytics offers a means to communicate the co-benefits and trade-offs that may emerge, as well as prioritise the AD strategies, based on the prioritization of criteria. Specifically, the method supports exploration of the social, environmental and economic impact of different AD strategies and decisions, linked to current issues, namely AD scale and adoption. The results highlight a trade-off between transport costs and social acceptability for the AD centralised versus decentralised strategies. When low carbon options are weighted higher then slow, steady and aggressive decentralised strategies are the best strategic adoption of AD. Conversely, when Energy production is considered a priority, then aggressive scaling up in a centralised approach is best with slow and steady approaches being further from the ideal. The framework has demonstrated that it permits a space for dialogue and transparent prioritization of AD strategies based on WEF nexus impacts.
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