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Inotropes are prescribed to enhance myocardial contractility while vasopressors serve to improve vascular tone. Although these medications remain a life-saving therapy in cardiovascular clinical scenarios with hemodynamic impairment, the paucity of evidence on these drugs makes the choice of the most appropriate vasoactive agent challenging. As such, deep knowledge of their pharmacological and hemodynamic effects becomes crucial to optimizing hemodynamic profile while reducing the potential adverse effects. Given this perspective, it is imperative for cardiologists to possess a comprehensive understanding of the underlying mechanisms governing these agents and to discern optimal strategies for their application across diverse clinical contexts. Thus, we briefly review these agents' pharmacological and hemodynamic properties and their reasonable clinical applications in cardiovascular settings. Critical interpretation of available data and the opportunities for future investigations are also highlighted.
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It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.
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In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents.
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Mitochondrial mutations have been linked to changes in phenotypes such as fertility or longevity, however, these changes have been often inconsistent across populations for unknown reasons. A hypothesis that could explain this inconsistency is that some still uncharacterized mitochondrial products are mediating the phenotypic changes across populations. It has been hypothesized that one such product could be the small RNAs encoded in the mitochondrial genome, thus this work will provide new evidence for their existence and function. By using data from the 1000 genome project and knowledge from previously characterized nuclear small RNAs, this study found that 10 small RNAs encoded in tRNA fragments are consistently expressed in 450 individuals from five different populations. Furthermore, this study demonstrated that the expression of some small mitochondrial RNAs is different in individuals of African ancestry, similar to what was observed before in nuclear and mitochondria mRNAs. Lastly, we investigate the causes behind these differences in expression, showing that at least one of the mt-tRFs might be regulated by TRMT10B. The analyses presented in this work further support the small mitochondrial RNAs as functional molecules, and their population-specific expression supports the hypothesis that they act as a mediator between the nucleus and mitochondria differently across populations.
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Linfócitos , RNA Mitocondrial , Humanos , RNA Mitocondrial/genética , Linfócitos/metabolismo , Transcrição Gênica , Mitocôndrias/genética , Mitocôndrias/metabolismoRESUMO
Epidermal club cells (ECCs) are present in many species of teleost fish. In an attempt to justify their presence in the epidermis of fish, they have been associated with numerous functions. One proposed function is communication with conspecifics during a predation event, as these cells may passively release substances upon rupture, which may occur during predation. We identified the presence and distribution of ECCs in the body skin of adult cardinal tetra, Paracheirodon axelrodi (Schultz, 1956) and analyzed the animal's behavioral response to conspecific skin extract in a laboratory setting. The identification and distribution of ECCs in the epidermis of the animals were confirmed by conventional histology and immunohistochemistry. Our results demonstrated that: ECCs are present in the skin of the entire body; a high density is observed in the dorsal side from head to tail, in the insertion of the fins and in the epidermis covering them; and ventral distribution is less extensive and more dispersed than dorsal distribution. Treatment of P. axelrodi specimens with skin preparations of conspecifics resulted in behavioral changes in the animals: they showed erratic swimming movements, they showed avoidance of the area of stimulus application and they decreased the time spent moving. Overall, these results allow us to conclude that P. axelrodi possesses ECCs throughout the body, with a greater presence in areas of high exposure to predation events (dorsal area and fins). Animals exposed to conspecific skin extract showed a significant increase in behaviors described as anti-predatory in other species. This supports the hypothesis that ECCs may be the origin of chemical alarm cues that are passively released when skin damage occurs, alerting the rest of the group to the risk of predation.
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Comportamento Predatório , Animais , Comportamento Predatório/fisiologia , Células Epidérmicas/fisiologia , Epiderme/fisiologia , Comportamento Animal/fisiologiaRESUMO
Recognizing and remembering another individual in a social context could be beneficial for individual fitness. Especially in agonistic encounters, remembering an opponent and the previous fight could allow for avoiding new conflicts. Considering this, we hypothesized that this type of social interaction forms a long-term recognition memory lasting several days. It has been shown that a second encounter 24 h later between the same pair of zebrafish males is resolved with lower levels of aggression. Here, we evaluated if this behavioral change could last for longer intervals and a putative mechanism associated with memory storage: the recruitment of NMDA receptors. We found that if a pair of zebrafish males fight and fight again 48 or 72 h later, they resolve the second encounter with lower levels of aggression. However, if opponents were exposed to MK-801 (NMDA receptor antagonist) immediately after the first encounter, they solved the second one with the same levels of aggression: that is, no reduction in aggressive behaviors was observed. These amnesic effect suggest the formation of a long-term social memory related to recognizing a particular opponent and/or the outcome and features of a previous fight.
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Agressão , Maleato de Dizocilpina , Consolidação da Memória , Memória de Longo Prazo , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Masculino , Agressão/fisiologia , Agressão/efeitos dos fármacos , Consolidação da Memória/fisiologia , Consolidação da Memória/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Memória de Longo Prazo/fisiologia , Memória de Longo Prazo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Reconhecimento Psicológico/fisiologia , Reconhecimento Psicológico/efeitos dos fármacos , Comportamento Social , Antagonistas de Aminoácidos Excitatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologiaRESUMO
Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.
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Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.
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It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.
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Fármacos Cardiovasculares , Doenças Cardiovasculares , Masculino , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Procedimentos Clínicos , Fatores de Risco de Doenças CardíacasRESUMO
Lakes are essentially interlinked to humans as they provide water for drinking, agriculture, industrial and domestic purposes. The upsurge of plastic usage, its persistence, and potential detrimental effects on organisms cause impacts on the trophic food web of freshwater ecosystems; this issue, however, still needs to be explored. Zooplankton worldwide is commonly studied as an indicator of environmental risk in aquatic ecosystems for several pollutants. The aim of the review is to link the existing knowledge of microplastic pollution in zooplankton to assess the potential risks linked to these organisms which are at the first level of the lacustrine trophic web. A database search was conducted through the main databases to gather the relevant literature over the course of time. The sensitivity of zooplankton organisms is evident from laboratory studies, whereas several knowledge gaps exist in the understanding of mechanisms causing toxicity. This review also highlights insufficient data on field studies hampering the understanding of the pollution extent in lakes, as well as unclear trends on ecosystem-level cascading effects of microplastics (MPs) and mechanisms of toxicity (especially in combination with other pollutants). Therefore, this review provides insight into understanding the overlooked issues of microplastic in lake ecosystems to gain an accurate ecological risk assessment.
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In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.
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Terapia de Ressincronização Cardíaca , Cardiologistas , Exposição à Radiação , Proteção Radiológica , Humanos , Exposição à Radiação/prevenção & controle , Radiação IonizanteRESUMO
It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.
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Chronic coronary syndrome (CCS), which encompasses a broad spectrum of clinical presentations of coronary artery disease (CAD), is the leading cause of morbidity and mortality worldwide. Recent guidelines for the management of CCS emphasize the dynamic nature of the CAD process, replacing the term "stable" with "chronic", as this disease is never truly "stable". Despite significant advances in the treatment of CAD, patients with CCS remain at an elevated risk of major cardiovascular events (MACE) due to the so-called residual cardiovascular risk. Several pathogenetic pathways (thrombotic, inflammatory, metabolic, and procedural) may distinctly contribute to the residual risk in individual patients and represent a potential target for newer preventive treatments. Identifying the level and type of residual cardiovascular risk is essential for selecting the most appropriate diagnostic tests and follow-up procedures. In addition, new management strategies and healthcare models could further support available treatments and lead to important prognostic benefits. This review aims to provide an overview of the diagnostic and therapeutic challenges in the management of patients with CCS and to promote more effective multidisciplinary care.
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The Sardinian grass snake, Natrix helvetica cetti, is an endangered endemic snake subspecies with a restricted and highly fragmented geographic distribution. Information on its ecology and detailed geographic distribution are scarce and may negatively impact on its conservation status. Therefore, a literature review on its taxonomy, morphology, ecology, and conservation is presented here. Moreover, field records from the authors, citizen science and the existing literature provide an updated geographic distribution highlighting its presence within 13 new and 7 historic 10 × 10 km cells. Bioclimatic niche modelling was then applied to explore patterns of habitat suitability and phenotypic variation within N. h. cetti. The geographic distribution of the species was found to be positively correlated with altitude and precipitation values, whereas temperature showed a negative correlation. Taken together, these outcomes may explain the snake's presence, particularly in eastern Sardinia. In addition, analysis of distribution overlap with the competing viperine snake (N. maura) and the urodeles as possible overlooked trophic resources (Speleomantes spp. and Euproctus platycephalus) showed overlaps of 66% and 79%, respectively. Finally, geographical or bioclimatic correlations did not explain phenotypic variation patterns observed in this highly polymorphic taxon. Perspectives on future research to investigate N. h. cetti's decline and support effective conservation measures are discussed.
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Nowadays, a progressive and exponential increase in the use of invasive and non-invasive instrumental diagnostics and therapeutic services has been shown. Although unnecessary, instrumental examinations are often largely prescribed, replacing clinical evaluation. Their correct use, on the contrary, would address precise epidemiological and clinical contexts. Therefore identifying whether a test or procedure is appropriate or not plays a crucial role in clinical practice. Several documents from scientific societies and expert groups indicate the most appropriate cardiovascular diagnostic and therapeutic procedures. The international Choosing Wisely campaign invited the main scientific societies to identify five techniques or treatments used in their field that are often unnecessary and may potentially damage patients. The Italian Association of Hospital Cardiologists (ANMCO) joined the project identifying the five cardiological practices in our country at greater risk of inappropriateness in 2014. This list has recently been updated. Moreover, possible solutions to this problem have been proposed.
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Cardiologistas , Cardiologia , Humanos , HospitaisRESUMO
Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.
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This work investigates the effectiveness of deep neural networks within the realm of battery charging. This is done by introducing an innovative control methodology that not only ensures safety and optimizes the charging current, but also substantially reduces the computational complexity with respect to traditional model-based approaches. In addition to their high computational costs, model-based approaches are also hindered by their need to accurately know the model parameters and the internal states of the battery, which are typically unmeasurable in a realistic scenario. In this regard, the deep learning-based methodology described in this work was been applied for the first time to the best of the authors' knowledge, to scenarios where the battery's internal states cannot be measured and an estimate of the battery's parameters is unavailable. The reported results from the statistical validation of such a methodology underline the efficacy of this approach in approximating the optimal charging policy.
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The interaction between environmental plastic and trace elements is an issue of concern. Understanding their interaction mechanisms is key to evaluate the potential threats for the environment. To this regard, consolidating confidence in extraction protocols can help in understanding the amount of different species present on plastic surface, as well as the potential mobility of trace elements present inside the plastic matrix (e.g., additives). Here we tested the efficacy of different reagents to mimic the elemental phases bonded to meso- and microplastic in the environment, in relation to the grade of ageing and the polymer composition. Results showed that a relatively high portion of trace elements is bonded in a weak phase and that other phases abundant in other matrices (e.g., oxides and bonded to organic matter) are only present to a limited degree in the plastic samples. The comparison of different sample types highlighted the important role of plastic ageing in governing interactions with trace elements, while the polymer composition has a limited influence on this process. Finally, the future steps toward a tailored extraction scheme for environmental plastic are proposed.
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Pollution by plastic and microplastic impacts the environment globally. Knowledge on the ageing mechanisms of plastics in natural settings is needed to understand their environmental fate and their reactivity in the ecosystems. Accordingly, the study of ageing processes is gaining focus in the context of the environmental sciences. However, laboratory-based experimental research has typically assessed individual ageing processes, limiting environmental applicability. In this study, we propose a multi-tiered approach to study the environmental ageing of polyethylene plastic fragments focusing on the combined assessment of physical and biological processes in sequence. The ageing protocol included ultraviolet irradiation in air and in a range of water solutions, followed by a biofouling test. Changes in surface characteristics were assessed by Fourier transform infrared spectroscopy, scanning electron microscopy, and water contact angle. UV radiation both in air and water caused a significant increase in the density of oxidized groups (i.e., hydroxyl and carbonyl) on the plastic surface, whereby water solution chemistry influenced the process both by modulating surface oxidation and morphology. Biofouling, too, was a strong determinant of surface alterations, regardless of the prior irradiation treatments. All biofouled samples present (i) specific infrared bands of new surface functional groups (e.g., amides and polysaccharides), (ii) a further increase in hydroxyl and carbonyl groups, (iii) the diffuse presence of algal biofilm on the plastic surface, and (iv) a significant decrease in surface hydrophobicity. This suggests that biological-driven alterations are not affected by the level of physicochemical ageing and may represent, in real settings, the main driver of alteration of both weathered and pristine plastics. This work highlights the potentially pivotal role of biofouling as the main process of plastic ageing, providing useful technical insights for future experimental works. These results also confirm that a multi-tiered laboratory approach permits a realistic simulation of plastic environmental ageing in controlled conditions.
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Plásticos , Poluentes Químicos da Água , Polietileno/análise , Ecossistema , Poluentes Químicos da Água/análise , Água , Monitoramento AmbientalRESUMO
The incidence of atrial fibrillation (AF) during pregnancy increases with maternal age and with the presence of structural heart disorders. Early diagnosis and prompt therapy can considerably reduce the risk of thromboembolism. The therapeutic approach to AF during pregnancy is particularly challenging, and the maternal and fetal risks associated with the use of antiarrhythmic and anticoagulant drugs must be carefully evaluated. Moreover, the currently used thromboembolic risk scores have yet to be validated for the prediction of stroke during pregnancy. At present, electrical cardioversion is considered to be the safest and most effective strategy in women with hemodynamic instability. Beta-selective blockers are also recommended as the first choice for rate control. Antiarrhythmic drugs such as flecainide, propafenone and sotalol should be considered for rhythm control if atrioventricular nodal-blocking drugs fail. AF catheter ablation is currently not recommended during pregnancy. Overall, the therapeutic strategy for AF in pregnancy must be carefully assessed and should take into consideration the advantages and drawbacks of each aspect. A multidisciplinary approach with a "Pregnancy-Heart Team" appears to improve the management and outcome of these patients. However, further studies are needed to identify the most appropriate therapeutic strategies for AF in pregnancy.