Factors associated with long hospitalisation for psychotic disorder patients in an acute ward: Tertiary care hospital.

Background: The average length of stay is often used to indicate health system efficiency; shorter stays are associated with reduced costs. In South Africa, mental healthcare expenditure is spent on inpatient care. Aim: To identify factors associated with a long stay in an acute psychiatric unit. Setting: A tertiary hospital. Methods: A case-control study review of inpatients diagnosed with psychotic symptoms was used. Sample was divided into two groups, length of stay (LOS) (LOS greater than 21 days, LOS less than 14 days). Total of 82 patients were divided into short stay group (SSG, n = 23) and long stay group (LSG) (n = 59). A comparison of demographic, clinical and system variables was conducted. Results: In demographics, LSG had fewer men compared to SSG (78.3%) and differed statistically from LSG with p = 0.05. Long stay groups were older in comparison to SSG with a p = 0.02. Illicit substance use in LSG was 44.1% and statistically less than SSG (73.91%; p = 0.02). A high proportion of LSG had medical or surgical and psychiatric comorbidities (67.8%) compared to SSG (43.5%) (p = 0.04). A total of 95% patients in SSG had family support. Conclusion: Longer stay was found to be associated with older females with primary psychotic disorders. Comorbidities with less availability of family support were associated with younger males presenting with psychotic symptoms that may be related to illicit substances that respond to rapid stabilisation. Contribution: Active surveillance of medical comorbidities amongst older female patients is necessary for early liaison services to reduce their length of stay.

Surveillance of adults with congenital heart disease: Current guidelines and actual clinical practice.

BACKGROUND AND AIM: Congenital heart disease (CHD) is the most common birth defect with prevalence of 0.8%. Thanks to tremendous progress in medical and surgical practice, nowadays, >90% of children survive into adulthood. Recently European Society of Cardiology (ESC), American College of Cardiology (ACC)/ American Heart Association (AHA) issued guidelines which offer diagnostic and therapeutic recommendations for the different defect categories. However, the type of technical exams and their frequency of follow-up may vary largely between clinicians and centres. We aimed to present an overview of available diagnostic modalities and describe current surveillance practices by cardiologists taking care of adults with CHD (ACHD). METHODS AND RESULTS: A questionnaire was used to assess the frequency cardiologists treating ACHD for at least one year administrated the most common diagnostic tests for ACHD. The most frequently employed diagnostic modalities were ECG and echocardiography for both mild and moderate/severe CHD. Sixty-seven percent of respondents reported that they routinely address psychosocial well-being. CONCLUSION: Differences exist between reported current clinical practice and published guidelines. This is particularly true for the care of patients with mild lesions. In addition, some differences exist between ESC and American guidelines, with more frequent surveillance suggested by the Americans.

Wound healing and Cadmium detoxification in the earthworm Lumbricus terrestris - a potential case for coelomocytes?

Earthworms are affected by physical stress, like injury, and by exposure to xenobiotics, such as the toxic metal cadmium (Cd), which enters the environment mainly through industry and agriculture. The stress response to the single and the combination of both stressors was examined in regenerative and unharmed tissue of Lumbricus terrestris to reveal if the stress response to a natural insult like injury (amputation) interferes with Cd detoxification mechanisms. We characterized the roles of metallothionein 1 (MT1) and MT2 isoforms, heat shock protein 70 as well as immune biomarkers such as the toll-like receptors (TLR) single cysteine cluster TLR and multiple cysteine cluster TLR. The role of the activated transcription factors (ATFs) ATF2, ATF7, and the cAMP responsive element binding protein as putative regulatory intersection as well as a stress-dependent change of the essential trace elements zinc and calcium was analyzed. Phosphorylated AMP activated protein kinase, the cellular energy sensor, was measured to explore the energy demand, while the energy status was determined by detecting carbohydrate and protein levels. Taken together, we were able to show that injury rather than Cd is the driving force that separates the four treatment groups - Control, Cd exposure, Injury, Cd exposure and injury. Interestingly, we found that gene expression differed regarding the tissue section that was analyzed and we hypothesize that this is due to the migration of coelomocytes, earthworm immune cells, that take over a key role in protecting the organism from a variety of environmental challenges. Surprisingly, we discovered a role for MT1 in the response to multiple stressors and an isoform-specific function for the two newly characterized TLRs. In conclusion, we gathered novel information on the relation of innate immunity, wound healing, and Cd detoxification mechanisms in earthworms.

Knock-in mice expressing a humanized arachidonic acid 15-lipoxygenase (Alox15) carry a partly dysfunctional erythropoietic system.

Arachidonic acid 15-lipoxygenases (ALOX15) play a role in mammalian erythropoiesis but they have also been implicated in inflammatory processes. Seven intact Alox genes have been detected in the mouse reference genome and the mouse Alox15 gene is structurally similar to the orthologous genes of other mammals. However, mouse and human ALOX15 orthologs have different functional characteristics. Human ALOX15 converts C20 polyenoic fatty acids like arachidonic acid mainly to the n-6 hydroperoxide. In contrast, the n-9 hydroperoxide is the major oxygenation product formed by mouse Alox15. Previous experiments indicated that Leu353Phe exchange in recombinant mouse Alox15 humanized the catalytic properties of the enzyme. To investigate whether this functional humanization might also work in vivo and to characterize the functional consequences of mouse Alox15 humanization we generated Alox15 knock-in mice (Alox15-KI), in which the Alox15 gene was modified in such a way that the animals express the arachidonic acid 15-lipoxygenating Leu353Phe mutant instead of the arachidonic acid 12-lipoxygenating wildtype enzyme. These mice develop normally, they are fully fertile but display modified plasma oxylipidomes. In young individuals, the basic hematological parameters were not different when Alox15-KI mice and outbred wildtype controls were compared. However, when growing older male Alox15-KI mice develop signs of dysfunctional erythropoiesis such as reduced hematocrit, lower erythrocyte counts and attenuated hemoglobin concentration. These differences were paralleled by an improved ex vivo osmotic resistance of the peripheral red blood cells. Interestingly, such differences were not observed in female individuals suggesting gender specific effects. In summary, these data indicated that functional humanization of mouse Alox15 induces defective erythropoiesis in aged male individuals.

Security Event-Trigger-Based Distributed Energy Management Of Cyber-Physical Isolated Power System With Considering Nonsmooth Effects.

Due to cyber-physical fusion and nonsmooth characteristics of energy management, this article proposes a security event-trigger-based distributed approach to address these issues with developed smoothing technique. To tackle with nonconvex and nondifferentiable issue, a randomized gradient-free-based successive convex approximation is developed to smooth economic objective function. Due to resilience ability against security issue, a security event-triggered mechanism-based distributed energy management is proposed to optimize social welfare, which coordinately controls both power generators and load demand. The security event-triggered mechanism is designed to reduce power system security risks, and relieve communication burden caused by smoothing calculation, the convergence of proposed distributed algorithm is also properly proved. According to those obtained results on both IEEE 9-bus and IEEE 39-bus systems, it reveals that the proposed approach can achieve good convergence performance and have less security risks than other alternatives, which also proves that the proposed approach can be a viable and promising way for tackling with energy management issue of cyber-physical isolated power system.

Humanization of the Reaction Specificity of Mouse Alox15b Inversely Modified the Susceptibility of Corresponding Knock-In Mice in Two Different Animal Inflammation Models.

Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in the pathogenesis of inflammatory diseases, and its pro- and anti-inflammatory effects have been reported for different ALOX-isoforms. Human ALOX15B oxygenates arachidonic acid to its 15-hydroperoxy derivative, whereas the corresponding 8-hydroperoxide is formed by mouse Alox15b (Alox8). This functional difference impacts the biosynthetic capacity of the two enzymes for creating pro- and anti-inflammatory eicosanoids. To explore the functional consequences of the humanization of the reaction specificity of mouse Alox15b in vivo, we tested Alox15b knock-in mice that express the arachidonic acid 15-lipoxygenating Tyr603Asp and His604Val double mutant of Alox15b, instead of the arachidonic acid 8-lipoxygenating wildtype enzyme, in two different animal inflammation models. In the dextran sodium sulfate-induced colitis model, female Alox15b-KI mice lost significantly more bodyweight during the acute phase of inflammation and recovered less rapidly during the resolution phase. Although we observed significant differences in the colonic levels of selected pro- and anti-inflammatory eicosanoids during the time-course of inflammation, there were no differences between the two genotypes at any time-point of the disease. In Freund's complete adjuvant-induced paw edema model, Alox15b-KI mice were less susceptible than outbred wildtype controls, though we did not observe significant differences in pain perception (Hargreaves-test, von Frey-test) when the two genotypes were compared. our data indicate that humanization of the reaction specificity of mouse Alox15b (Alox8) sensitizes mice for dextran sodium sulfate-induced experimental colitis, but partly protects the animals in the complete Freund's adjuvant-induced paw edema model.

Are standard aquatic test species and methods adequate surrogates for use in environmental risk assessment of pesticides in tropical environments?

In regulatory risk assessment, surrogate species of fish, aquatic invertebrates, and primary producers are tested to assess toxicity and subsequently the risk of pesticides to freshwater biota. This study evaluates whether the standard, surrogate test species (mostly temperate in latitudinal distribution) used in many parts of the world are suitable surrogates for first-tier risk assessments involving tropical freshwater biota. Data for the toxicity of pesticides to tropical fish, invertebrates, and primary producer species were extracted from the USEPA ECOTOX database and peer-reviewed literature. For each pesticide, the most sensitive regulatory endpoint extracted from the US Environmental Protection Agency (USEPA) and European Food Safety Authority (EFSA) dossiers for freshwater fish, invertebrates, and primary producers was selected. The ratios of the endpoint for tropical species and for the most sensitive regulatory endpoint for the appropriate taxonomic group were determined. A value >1 indicates that the tropical species is less sensitive than the respective standard regulatory species. Tropical fish species were less sensitive than standard fish species in 84% of the comparisons, and in 93.5% of the comparisons, tropical fish were less or similarly sensitive (within a factor of 5). For aquatic invertebrates, 78.1% of the evaluated tropical species were less sensitive than standard species and 93.3% of tropical invertebrates species were less or similarly sensitive. For primary producers, 96% of tropical species were less sensitive than standard test species. Overall, standard species used globally were more sensitive or similarly sensitive compared to tropical species in more than 93% of the cases. In conclusion, the data show that freshwater toxicity data for pesticides from tests using standard test species, tested according to international accepted guidelines, are appropriate for use in first-tier risk assessments for tropical environments. Integr Environ Assess Manag 2023;19:202-212. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Two-Layered Hierarchical Optimization Strategy With Distributed Potential Game for Interconnected Hybrid Energy Systems.

Due to the existence of different stakeholders, it makes competitive game characteristic in hybrid energy systems (HESs). Combined with the high-dimensional complexity and output uncertainty of distributed energy resources, the optimal operation of HESs can be a more challenging problem. Here, this article proposes a potential game-based two-layered hierarchical optimization strategy to deal with this problem. With consideration of its high-dimensional complexity, a two-layered hierarchical HES model is created, consisting of an upper-level and a lower-level model. For properly solving competitive relationships among different stakeholders in the upper-level model, a multiagent system for stakeholders is created and a potential game is employed with a distributed primal-dual perturbed algorithm, and its convergence and optimality have been both proved. Moreover, an uncertainty and robustness analysis is done with coordination between lower and upper models, which deduces a feasible robust uncertainty interval in the lower-level model. For better dealing with the lower-level model, a gradient descent-based multiobjective differential evolution (GD-MODE) algorithm is utilized to optimize the economic cost and emission issue simultaneously, producing a set of Pareto-optimal schemes. Combined with simulation results, it is proven that the proposed method can reduce computational complexity as well as properly deal with uncertainty problems for the optimal operation of HESs.

Comparative exploration of the morphological plasticity of Trichodina centrostrigeata (Peritrichia: Mobilida), ectoparasite from the gills of two tilapia species (Oreochromis niloticus and O. mossambicus) in a global context.

Trichodina centrostrigeata Basson, Van As et Paperna, 1983 from Oreochromis mossambicus (Peters) and O. niloticus (Linnaeus) from different host populations from Argentina, Mexico and South Africa was reviewed. Although T. centrostrigeata has a distinct denticle structure that makes morphological taxonomic inferences uncomplicated, variation of the denticles within and among individuals and populations were still observed. While traditional taxonomy of mobilines is heavily reliant on morphometrics, and recently even more so on molecular analysis, this paper proposes the use of geometric morphometry, specifically elliptical Fourier analysis, to address morphological conflicts that arise when comparing different populations. By applying this technique, combined with traditional taxonomy, it was found that T. centrostrigeata in this study can be grouped into two separate morphotypes, the first (type a) from aquaculture farms in Argentina and Mexico and the second (type b) from a natural habitat in Glen Alpine Dam, South Africa. This study supports the validity of geometric morphometry as an additional technique to distinguish not only between species but also evolutionary plasticity of the same species from different localities and habitats.

Quantum-Safe Group Key Establishment Protocol from Lattice Trapdoors.

Group communication enables Internet of Things (IoT) devices to communicate in an efficient and fast manner. In most instances, a group message needs to be encrypted using a cryptographic key that only devices in the group know. In this paper, we address the problem of establishing such a key using a lattice-based one-way function, which can easily be inverted using a suitably designed lattice trapdoor. Using the notion of a bad/good basis, we present a new method of coupling multiple private keys into a single public key, which is then used for encrypting a group message. The protocol has the apparent advantage of having a conjectured resistance against potential quantum-computer-based attacks. All functions-key establishment, session key update, node addition, encryption, and decryption-are effected in constant time, using simple linear-algebra operations, making the protocol suitable for resource-constrained IoT networks. We show how a cryptographic session group key can be constructed on the fly by a user with legitimate credentials, making node-capture-type attacks impractical. The protocol also incorporates a mechanism for node addition and session-key generation in a forward- and backward-secrecy-preserving manner.

Male Knock-in Mice Expressing an Arachidonic Acid Lipoxygenase 15B (Alox15B) with Humanized Reaction Specificity Are Prematurely Growth Arrested When Aging.

Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in cell differentiation and in the pathogenesis of inflammation. The mouse genome involves seven functional Alox genes and the encoded enzymes share a high degree of amino acid conservation with their human orthologs. There are, however, functional differences between mouse and human ALOX orthologs. Human ALOX15B oxygenates arachidonic acid exclusively to its 15-hydroperoxy derivative (15S-HpETE), whereas 8S-HpETE is dominantly formed by mouse Alox15b. The structural basis for this functional difference has been explored and in vitro mutagenesis humanized the reaction specificity of the mouse enzyme. To explore whether this mutagenesis strategy may also humanize the reaction specificity of mouse Alox15b in vivo, we created Alox15b knock-in mice expressing the arachidonic acid 15-lipoxygenating Tyr603Asp+His604Val double mutant instead of the 8-lipoxygenating wildtype enzyme. These mice are fertile, display slightly modified plasma oxylipidomes and develop normally up to an age of 24 weeks. At later developmental stages, male Alox15b-KI mice gain significantly less body weight than outbred wildtype controls, but this effect was not observed for female individuals. To explore the possible reasons for the observed gender-specific growth arrest, we determined the basic hematological parameters and found that aged male Alox15b-KI mice exhibited significantly attenuated red blood cell parameters (erythrocyte counts, hematocrit, hemoglobin). Here again, these differences were not observed in female individuals. These data suggest that humanization of the reaction specificity of mouse Alox15b impairs the functionality of the hematopoietic system in males, which is paralleled by a premature growth arrest.

A Three-Stage Optimal Operation Strategy of Interconnected Microgrids With Rule-Based Deep Deterministic Policy Gradient Algorithm.

The ever-increasing requirements of demand response dynamics, competition among different stakeholders, and information privacy protection intensify the challenge of the optimal operation of microgrids. To tackle the above problems, this article proposes a three-stage optimization strategy with a deep reinforcement learning (DRL)-based distributed privacy optimization. In the upper layer of the model, the rule-based deep deterministic policy gradient (DDPG) algorithm is proposed to optimize the load migration problem with demand response, which enhances dynamic characteristics with the interaction between electricity prices and consumer behavior. Due to the competition among different stakeholders and the information privacy requirement in the middle layer of the model, a potential game-based distributed privacy optimization algorithm is improved to seek Nash equilibriums (NEs) with encoded exchange information by a distributed privacy-preserving optimization algorithm, which can ensure the convergence as well as protect privacy information of each stakeholder. In the lower layer of the model of each stakeholder, economic cost and emission rate are both taken as operation objectives, and a gradient descent-based multiobjective optimization method is employed to approach this objective. The simulation results confirm that the proposed three-stage optimization strategy can be a viable and efficient way for the optimal operation of microgrids.

The Reaction Specificity of Mammalian ALOX15 Orthologs is Changed During Late Primate Evolution and These Alterations Might Offer Evolutionary Advantages for Hominidae.

Arachidonic acid lipoxygenases (ALOXs) have been implicated in the immune response of mammals. The reaction specificity of these enzymes is decisive for their biological functions and ALOX classification is based on this enzyme property. Comparing the amino acid sequences and the functional properties of selected mammalian ALOX15 orthologs we previously hypothesized that the reaction specificity of these enzymes can be predicted based on their amino acid sequences (Triad Concept) and that mammals, which are ranked in evolution below gibbons, express arachidonic acid 12-lipoxygenating ALOX15 orthologs. In contrast, Hominidae involving the great apes and humans possess 15-lipoxygenating enzymes (Evolutionary Hypothesis). These two hypotheses were based on sequence data of some 60 mammalian ALOX15 orthologs and about half of them were functionally characterized. Here, we compared the ALOX15 sequences of 152 mammals representing all major mammalian subclades expressed 44 novel ALOX15 orthologs and performed extensive mutagenesis studies of their triad determinants. We found that ALOX15 genes are absent in extant Prototheria but that corresponding enzymes frequently occur in Metatheria and Eutheria. More than 90% of them catalyze arachidonic acid 12-lipoxygenation and the Triad Concept is applicable to all of them. Mammals ranked in evolution above gibbons express arachidonic acid 15-lipoxygenating ALOX15 orthologs but enzymes with similar specificity are only present in less than 5% of mammals ranked below gibbons. This data suggests that ALOX15 orthologs have been introduced during Prototheria-Metatheria transition and put the Triad Concept and the Evolutionary Hypothesis on a much broader and more reliable experimental basis.

Resilient Optimal Defensive Strategy of Micro-Grids System via Distributed Deep Reinforcement Learning Approach Against FDI Attack.

The ever-increasing false data injection (FDI) attack on the demand side brings great challenges to the energy management of interconnected microgrids. To address those aspects, this article proposes a resilient optimal defensive strategy with the distributed deep reinforcement learning (DRL) approach. To evaluate the FDI attack on demand response (DR), an online evaluation approach with the recursive least-square (RLS) method is proposed to evaluate the extent of supply security or voltage stability of the microgrids system is affected by the FDI attack. On the basis of evaluated security confidence, a distributed actor network learning approach is proposed to deduce optimal network weight, which can generate an optimal defensive scheme to ensure the economic and security issue of the microgrids system. From the methodology's view, it can also enhance the autonomy of each microgrid as well as accelerate DRL efficiency. According to those simulation results, it can reveal that the proposed method can evaluate FDI attack impact well and an improved distributed DRL approach can be a viable and promising way for the optimal defense of microgrids against the FDI attack on the demand side.

DNA Methylation and Detoxification in the Earthworm Lumbricus terrestris Exposed to Cadmium and the DNA Demethylation Agent 5-aza-2'-deoxycytidine.

Earthworms are well-established model organisms for testing the effects of heavy metal pollution. How DNA methylation affects cadmium (Cd) detoxification processes such as the expression of metallothionein 2 (MT2), however, is largely unknown. We therefore exposed Lumbricus terrestris to 200 mg concentrations of Cd and 5-aza-2'-deoxycytidine (Aza), a demethylating agent, and sampled tissue and coelomocytes, cells of the innate immune system, for 48 h. MT2 transcription significantly increased in the Cd- and Cd-Aza-treated groups. In tissue samples, a significant decrease in MT2 in the Aza-treated group was detected, showing that Aza treatment inhibits basal MT2 gene activity but has no effect on Cd-induced MT2 levels. Although Cd repressed the gene expression of DNA-(cytosine-5)-methyltransferase-1 (DNMT1), which is responsible for maintaining DNA methylation, DNMT activity was unchanged, meaning that methylation maintenance was not affected in coelomocytes. The treatment did not influence DNMT3, which mediates de novo methylation, TET gene expression, which orchestrates demethylation, and global levels of hydroxymethylcytosine (5hmC), a product of the demethylation process. Taken together, this study indicates that Aza inhibits basal gene activity, in contrast to Cd-induced MT2 gene expression, but does not affect global DNA methylation. We therefore conclude that Cd detoxification based on the induction of MT2 does not relate to DNA methylation changes.

Discrimination of the Activity of Low-Affinity Wild-Type and High-Affinity Mutant Recombinant BoNT/B by a SIMA Cell-Based Reporter Release Assay.

Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data.

Static and Dynamic Event-Triggered Mechanisms for Distributed Secondary Control of Inverters in Low-Voltage Islanded Microgrids.

Due to the high resistance/reactance (R/X) ratio of a low-voltage microgrid (LVMG), virtual complex impedance-based P-· V/Q-ω droop control is adopted in this article as the primary control (PC) technique for stabilizing the system. A distributed event-triggered restoration mechanism (ETSM) is proposed as the secondary control (SC) technique to restore the output-voltage frequency and improve power sharing accuracy. The proposed ETSM ensures that neighboring communication happens only at some discrete instants when a predefined event-triggering condition (ETC) is fulfilled. In general, the design of the ETC is the crucial challenge of an event-triggered mechanism (ETM). Thus, in this article, a static ETM (SETM) is proposed as the ETC at first, where two static parameters are utilized to reduce the triggering frequency. Bounded stability is ensured under the SETM, which means that the output-voltage frequency is restored to the vicinity of its nominal value, and close to fair utilization of the distributed generators (DGs) is achieved. To further improve the power sharing accuracy and accelerate the regulation process, a dynamic ETM (DETM) is then introduced. In the DETM, two dynamic parameters that converge to zero in the steady state are designed, which promises asymptotic stability of the system. Besides, Zeno behavior is excluded in both mechanisms. An LVMG consisting of four DGs is constructed in MATLAB/Simulink to illustrate the effectiveness of the proposed methods, and the simulations correspond with our theoretical analysis.

Common mechanisms cannot explain time- and dose-dependent DNA methylation changes in earthworms exposed to cadmium.

DNA hypermethylation caused by environmental pollutants like cadmium (Cd) has already been demonstrated in many invertebrates, including earthworms. However, the exact epigenetic mechanisms that drive this hypermethylation are largely unknown and even basic DNA methylation and demethylation processes are hardly characterized. Therefore, we used an important bioindicator, the earthworm Lumbricus terrestris, as a model organism to determine time- and dose-dependent effects of Cd on global and gene-specific DNA methylation and its underlying mechanisms. We revealed Cd-induced adenine and cytosine hypermethylation using specific antibodies in dot blots and found that the methylation level of adenine compared to cytosine changed even to a bigger extent. However, the levels of hydroxymethylated cytosine did not differ between treatment groups. General methylation and demethylation components like methyltransferases (DNMT1 and 3), and ten-eleven translocation (TET) genes were confirmed in L. terrestris by quantitative RealTime PCR. However, neither gene expression, nor DNMT and TET enzyme activity showed significant differences in the Cd exposure groups. Using bisulfite conversion and sequencing, gene body methylation (gbm) of metallothionein 2 (MT2), one of the most important detoxification proteins, was characterized. Cd-dependent changes in MT2 gbm could, however, not be correlated to MT2 gene activity evaluated by quantitative RealTime PCR. Future directions as well as missing links are discussed in the present study hinting towards the importance of studying epigenetic marks and mechanistic insights in a broad variety of species to deepen our knowledge on the effects of changing environmental conditions.

Predicting Survival in Repaired Tetralogy of Fallot: A Lesion-Specific and Personalized Approach.

OBJECTIVES: This study sought to identify patients with repaired tetralogy of Fallot (rTOF) at high risk of death and malignant ventricular arrhythmia (VA). BACKGROUND: To date there is no robust risk stratification scheme to predict outcomes in adults with rTOF. METHODS: Consecutive patients were prospectively recruited for late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to define right and left ventricular (RV, LV) fibrosis in addition to proven risk markers. RESULTS: The primary endpoint was all-cause mortality. Of the 550 patients (median age 32 years, 56% male), 27 died (mean follow-up 6.4 ± 5.8; total 3,512 years). Mortality was independently predicted by RVLGE extent, presence of LVLGE, RV ejection fraction ≤47%, LV ejection fraction ≤55%, B-type natriuretic peptide ≥127 ng/L, peak exercise oxygen uptake (V02) ≤17 mL/kg/min, prior sustained atrial arrhythmia, and age ≥50 years. The weighted scores for each of the preceding independent predictors differentiated a high-risk subgroup of patients with a 4.4%, annual risk of mortality (area under the curve [AUC]: 0.87; P < 0.001). The secondary endpoint (VA), a composite of life-threatening sustained ventricular tachycardia/resuscitated ventricular fibrillation/sudden cardiac death occurred in 29. Weighted scores that included several predictors of mortality and RV outflow tract akinetic length ≥55 mm and RV systolic pressure ≥47 mm Hg identified high-risk patients with a 3.7% annual risk of VA (AUC: 0.79; P < 0.001) RVLGE was heavily weighted in both risk scores caused by its strong relative prognostic value. CONCLUSIONS: We present a score integrating multiple appropriately weighted risk factors to identify the subgroup of patients with rTOF who are at high annual risk of death who may benefit from targeted therapy.