Takotsubo syndrome (TTS) is an acute cause of heart failure characterized by a reversible left ventricular (LV) impairment usually induced by a physical or emotional trigger. TTS is not always a ...benign disease since it is associated with a relatively higher risk of life-threatening complications, such as cardiogenic shock, ventricular arrhythmias, respiratory failure, cardiopulmonary resuscitation and death. Despite notable advancements in the management of patients with TTS, physiopathological mechanisms underlying transient LV dysfunction remain largely unknown. Since TTS carries similar prognostic implications than acute myocardial infarction, the identification of mechanisms and predictors of worse prognosis remain key to establish appropriate treatments. The greater prevalence of TTS among post-menopausal women and the activation of the neuro-cardiac axis triggered by physical or emotional stressors paved the way forward to several studies focused on coronary microcirculation and impaired blood flow as the main physiopathological mechanisms of TTS. However, whether microvascular dysfunction is the cause or a consequence of transient LV impairment remains still unsettled. This review provides an up-to-date summary of available evidence supporting the role of microvascular dysfunction in TTS pathogenesis, summarizing contemporary invasive and non-invasive diagnostic techniques for its assessment. We will also discuss novel techniques focused on microvascular dysfunction in TTS which may support clinicians for the implementation of tailored treatments.Takotsubo syndrome (TTS) is an acute cause of heart failure characterized by a reversible left ventricular (LV) impairment usually induced by a physical or emotional trigger. TTS is not always a benign disease since it is associated with a relatively higher risk of life-threatening complications, such as cardiogenic shock, ventricular arrhythmias, respiratory failure, cardiopulmonary resuscitation and death. Despite notable advancements in the management of patients with TTS, physiopathological mechanisms underlying transient LV dysfunction remain largely unknown. Since TTS carries similar prognostic implications than acute myocardial infarction, the identification of mechanisms and predictors of worse prognosis remain key to establish appropriate treatments. The greater prevalence of TTS among post-menopausal women and the activation of the neuro-cardiac axis triggered by physical or emotional stressors paved the way forward to several studies focused on coronary microcirculation and impaired blood flow as the main physiopathological mechanisms of TTS. However, whether microvascular dysfunction is the cause or a consequence of transient LV impairment remains still unsettled. This review provides an up-to-date summary of available evidence supporting the role of microvascular dysfunction in TTS pathogenesis, summarizing contemporary invasive and non-invasive diagnostic techniques for its assessment. We will also discuss novel techniques focused on microvascular dysfunction in TTS which may support clinicians for the implementation of tailored treatments.
The successful handling of large semiconductor wafers is crucial for scaling up their production. Early-stage warpage control allows the prevention of undesirable asymmetric warpage, known as wafer ...bifurcation or buckling. Indeed, even in a gravity-free environment, thinning an 8″ or 12″ semiconductor wafer can result in warpage and bifurcation. To mitigate this issue, the taiko method, which involves creating a thicker ring region around the rim of the wafer, has been widely used. Previous research has focused on the theoretical factors affecting the warpage of a backside metalized taiko wafer. This work extends the case to a front-side metalized taiko wafer and introduces the concept of the equivalent thickness of a taiko wafer. The equivalent thickness of a taiko wafer, influenced by the ring region, lies in between the thickness of the central region and that of the annular region. Because of the limited number of taiko wafers that can be produced on a production line, modelling can be beneficial. In this work we compared the results of a developed analytical model with those obtained from a finite element analysis (FEA) approach with ANSYSY® Mechanical Enterprise 2022/R2 software to model the equivalent thickness of a taiko wafer. We investigated the curvature as a function of the stress of the metal layer, considering key design factors such as the substrate region thickness, the thickness of the thin metal film, the step height, and the width of the ring region. By systematically varying the thickness of the central region of the taiko wafer, we explored the curvature as a function of stress induced by thermal load in the linear regime and determined the slopes in the linear region of the curvature vs. stress curves. The aim of this study is to identify regularities and similarities with the Stoney equation and investigate the validity of the analytical approach for the case of a taiko substrate. The results show that there is a good agreement between the analytical model of a taiko wafer and the numerical analysis gained by the FEA methods.
Left ventricular pseudoaneurysms (LVP) are rare but may arise after myocardial infarction, trauma or cardiac surgery, tending to expand and rupture over the time. We show the case of a 75-year-old ...patient with a recurrent giant ventricular pseudoaneurysm, who presented to the emergency department with sustained ventricular tachycardia. Pseudoaneurysmatic lesion was investigated through echocardiography, angiography and Cardiac Computed Tomography, in order to evaluate the size and spatial orientation of the pseudoaneurysm and to set a tailored treatment. At emergency department, sustained ventricular tachycardia may be the first and unique clinical presentation of ventricular pseudoaneurysm late recurrence, whose management requires a multimodality imaging approach to guide surgical correction.
The prognostic relevance of periprocedural myocardial infarction (PMI) in patients with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI) is still matter of debate, ...particularly regarding the type (cardiac troponin or creatin kinase-MB) and different thresholds of biomarkers elevation, as the importance of associated ancillary criteria of ischemia or concomitant angiographic complications. There are still uncertainties regarding the value of PMI as event which is prognostically equivalent to spontaneous myocardial infarction or if it simply represents a marker of baseline risk, atherosclerotic burden and procedural complexity. In the present review, we will present the mechanisms and predictors of PMI occurring during PCI and potential treatment strategies to reduce its occurrence. We will also overview all commonly adopted definitions of PMI, which carry different prevalence and prognostic implications in daily practice and clinical trials. Finally, we will discuss the impact of different PMI definitions on the interpretation of trials results, emphasizing the importance of adequate endpoints selection in the planning and interpretation of clinical trials.The prognostic relevance of periprocedural myocardial infarction (PMI) in patients with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI) is still matter of debate, particularly regarding the type (cardiac troponin or creatin kinase-MB) and different thresholds of biomarkers elevation, as the importance of associated ancillary criteria of ischemia or concomitant angiographic complications. There are still uncertainties regarding the value of PMI as event which is prognostically equivalent to spontaneous myocardial infarction or if it simply represents a marker of baseline risk, atherosclerotic burden and procedural complexity. In the present review, we will present the mechanisms and predictors of PMI occurring during PCI and potential treatment strategies to reduce its occurrence. We will also overview all commonly adopted definitions of PMI, which carry different prevalence and prognostic implications in daily practice and clinical trials. Finally, we will discuss the impact of different PMI definitions on the interpretation of trials results, emphasizing the importance of adequate endpoints selection in the planning and interpretation of clinical trials.
Radial deficiencies (RDs), defined as under/abnormal development or absence of any of the
structures of the forearm, radial carpal bones and thumb, occur with a live birth incidence ranging
from 1 ...out of 30,000 to 1 out 6,000 newborns and represent about one third/one fourth of all the congenital
upper limb anomalies. About half of radial disorders have a mendelian cause and pattern of
inheritance, whereas the remaining half appears sporadic with no known gene involved. In sporadic
forms certain anomalies, such as thumb or radial hypoplasia, may occur either alone or in association
with systemic conditions, like vertebral abnormalities or renal defects. All the cases with a mendelian inheritance are syndromic
forms, which include cardiac defects (in Holt-Oram syndrome), bone marrow failure (in Fanconi anemia), platelet
deficiency (in thrombocytopenia-absent-radius syndrome), ocular motility impairment (in Okihiro syndrome). The
genetics of radial deficiencies is complex, characterized by genetic heterogeneity and high inter- and intra-familial clinical
variability: this review will analyze the etiopathogenesis and the genotype/phenotype correlations of the main radial deficiency
disorders in humans.
Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic disorder of progressive heterotopic ossification (HO). Here, we report a patient with an ultra-rare point mutation c.619C>G, p.Q207E ...located in a codon adjacent to the most common FOP mutation c.617G>A, p.R206H of Activin A Receptor, type 1 (ACVR1) and that affects the same intracellular amino acid position in the GS activation domain as the engineered constitutively active (c.a.) variant p.Q207D. It was predicted that both mutations at residue 207 have similar functional effects by introducing a negative charge. Transgenic p.Q207D-c.a. mice have served as a model for FOP HO in several in vivo studies. However, we found that the engineered ACVR1(Q207D-c.a.) is significantly more active than the classic FOP mutation ACVR1(R206H) when overexpressed in chicken limbs and in differentiation assays of chondrogenesis, osteogenesis and myogenesis. Importantly, our studies reveal that the ACVR1(Q207E) resembles the classic FOP receptor in these assays, not the engineered ACVR1(Q207D-c.a.). Notably, reporter gene assays revealed that both naturally occurring FOP receptors (ACVR1(R206H) and ACVR1(Q207E)) were activated by BMP7 and were sensitive to deletion of the ligand binding domain, whereas the engineered ACVR1(Q207D-c.a.) exhibited ligand independent activity. We performed an in silico analysis and propose a structural model for p.Q207D-c.a. that irreversibly relocates the GS domain into an activating position, where it becomes ligand independent. We conclude that the engineered p.Q207D-c.a. mutation has severe limitations as a model for FOP, whereas the naturally occurring mutations p.R206H and p.Q207E facilitate receptor activation, albeit in a reversible manner.
We investigate the microstructural evolution of electrochemically deposited poly-crystalline Cu films during subsequent thermal process cycles at mild maximum temperatures, compatible with the ...integration in advanced metallization schemes for electronic device manufacturing. The modifications induced by the thermal budget have been characterized at different scales (from the film-substrate interface to the wafer scale) with different complementary techniques: X-ray Diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and dynamical warpage measurements. Moreover, the film internal grains’ evolution has been modelled by a tri-dimensional on-cell model, derived by the Pott-like multi-states configurational energy dependence, able to consider multiple orientation of the grains and densification kinetics in the canonical ensemble. Finally, a macroscopic model of the warpage dependence on the process conditions is discussed. The presented joint theoretical and experimental analysis provides a complete and consistent scenario of the grain densification phenomenon and its impact for the Cu film microstructure and the composite system morphology, indicating several strategies for the integration of the process in real device structures.
PDF
