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Suicide is a huge deal in general public health, representing the second cause of mortality in young people worldwide. The suicidal setting analysis is usually performed through psychological autopsy, a method of investigation commonly used to study what leads to suicide. Psychological autopsy, though, requires the involvement of family and friends, or the finding of a diary or a suicide note. Nowadays, this is not always possible, especially during adolescence, the more if we consider new categories of people that are more used to live in a web dimension, than in a real one. So, with the advent of a new kind of social system including the web, psychological autopsy, as we know it, is not enough to determine the setting of an event. We here report the case of a 17-year old girl who committed suicide by hanging down from her house, leaving no suicide note. We propose a new investigation method developed through the analysis of phone messages and Facebook profile in order to better reconstruct the event. Although the standing difficulties in reconsidering the intimate motivations leading to such a decision, psychological autopsy nowadays needs to consider also social networks in order to prevent similar situations and even reconstruct the psychological dimension of the fact. We propose a model of Social-mobile autopsy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration., Areas Covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial. The in vivo test of somatic reprogramming and cardioregenerative non-coding RNAs revived the interest in gene therapy for myocardial regeneration. The latter, together with the advent of genome editing, has prompted most recent efforts to produce genetically-modified allogeneic CSCs that secrete cardioregenerative factors to optimize effective myocardial repair., Expert Opinion: The current war against heart failure epidemics in western countries seeks to find effective treatments to set back the failing hearts prolonging human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing regenerative agents are a novel and evolving therapy set to be affordable, safe, effective and available at all times for myocardial regeneration to either prevent or treat heart failure.

Scuba diving is an increasingly common recreational activity. We describe the physiopathology of barotrauma in two cases where death was caused by pulmonary barotrauma while diving. An inspection and autopsy were carried out in both cases. The autopsy data were supported by post-mortem radiological investigation. Histological and toxicological analyses were also carried out, and dive computer and tank manometer analysis performed. In both cases, the cause of death was attributable to arterial gas embolism, resulting from pulmonary barotrauma subsequent to pulmonary over-distension. The dive computer analysis and the tank manometer allowed us to understand what happened underwater. In our opinion, a multidisciplinary approach is crucial in order to clarify the cause of death. Some pathological conditions and risk factors should be considered before diving.

Introduction: "Bolus death" or "Café Coronary syndrome" refers to death due to asphyxia caused by an occlusion of the upper airways due to food. In this kind of asphyxia, the food bolus obstructs the larynx or the bronchial branches. This kind of event often affects subjects with acute intoxication due to alcohol or drugs, or with edentulism and with neurological or psychiatric diseases., Case Report: An elderly woman, suffering from schizophrenia, was found dead in her house due to food bolus asphyxia. The post-mortem toxicological analysis on the deceased's biological fluids revealed the presence of tricyclic antidepressants, antipsychotics and neuroleptics. Study of the oral cavity showed the presence of partial edentulism and periodontal disease., Hypothesis: We hypothesize that this kind of asphyxia in adults can be prevented. We believe that there are two major preventable factors: edentulism and salivation disorders in elderly and neuropsychiatric patients. The primary prevention of these pathologies would deal with the basic physician, similarly to other screenings already effectively in place., Conclusions: It is possible to prevent fatal asphyxia in subjects who suffer from this kind of diseases through appropriate screening. This prevention strategy would greatly reduce the amount of choking deaths in adults., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The adult mammalian heart, including the human, is unable to regenerate segmental losses after myocardial infarction. This evidence has been widely and repeatedly used up-to-today to suggest that the myocardium, contrary to most adult tissues, lacks an endogenous stem cell population or more specifically a bona-fide cardiomyocyte-generating progenitor cell of biological significance. In the last 15 years, however, the field has slowly evolved from the dogma that no new cardiomyocytes were produced from shortly after birth to the present consensus that new cardiomyocytes are formed throughout lifespan. This endogenous regenerative potential increases after various forms of injury. Nevertheless, the degree/significance and more importantly the origin of adult new cardiomyocytes remains strongly disputed. Evidence from independent laboratories has shown that the adult myocardium harbours bona-fide tissue-specific cardiac stem cells (CSCs). Their transplantation and in situ activation have demonstrated the CSCs regenerative potential and have been used to develop regeneration protocols which in pre-clinical tests have shown to be effective in the prevention and treatment of heart failure. Recent reports purportedly tracking the c-kit + CSC's fate using Cre/lox recombination in the mouse have challenged the existence and regenerative potential of the CSCs and have raised scepticism about their role in myocardial homeostasis and regeneration. The validity of these reports, however, is controversial because they failed to show that the experimental approach used is capable to both identify and tract the fate of the CSCs. Despite these serious shortcomings, in contraposition to the CSCs, these publications have proposed the proliferation of existing adult fully-matured cardiomyocytes as the relevant mechanism to explain cardiomyocyte renewal in the adult. This review critically ponders the available evidence showing that the adult mammalian heart possesses a definable myocyte-generating progenitor cell of biological significance. This endogenous regenerative potential is expected to provide the bases for novel approaches of myocardial repair in the near future., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Ischemic Heart Disease (IHD) remains the developed world's number one killer. The improved survival from Acute Myocardial Infarction (AMI) and the progressive aging of western population brought to an increased incidence of chronic Heart Failure (HF), which assumed epidemic proportions nowadays. Except for heart transplantation, all treatments for HF should be considered palliative because none of the current therapies can reverse myocardial degeneration responsible for HF syndrome. To stop the HF epidemic will ultimately require protocols to reduce the progressive cardiomyocyte (CM) loss and to foster their regeneration. It is now generally accepted that mammalian CMs renew throughout life. However, this endogenous regenerative reservoir is insufficient to repair the extensive damage produced by AMI/IHD while the source and degree of CM turnover remains strongly disputed. Independent groups have convincingly shown that the adult myocardium harbors bona-fide tissue specific cardiac stem cells (CSCs). Unfortunately, recent reports have challenged the identity and the endogenous myogenic capacity of the c-kit expressing CSCs. This has hampered progress and unless this conflict is settled, clinical tests of repair/regenerative protocols are unlikely to provide convincing answers about their clinical potential. Here we review recent data that have eventually clarified the specific phenotypic identity of true multipotent CSCs. These cells when coaxed by embryonic cardiac morphogens undergo a precisely orchestrated myogenic commitment process robustly generating bona-fide functional cardiomyocytes. These data should set the path for the revival of further investigation untangling the regenerative biology of adult CSCs to harness their potential for HF prevention and treatment.

Multipotent adult resident cardiac stem cells (CSCs) were first identified by the expression of c-kit, the stem cell factor receptor. However, in the adult myocardium c-kit alone cannot distinguish CSCs from other c-kit-expressing (c-kit pos ) cells. The adult heart indeed contains a heterogeneous mixture of c-kit pos cells, mainly composed of mast and endothelial/progenitor cells. This heterogeneity of cardiac c-kit pos cells has generated confusion and controversy about the existence and role of CSCs in the adult heart. Here, to unravel CSC identity within the heterogeneous c-kit-expressing cardiac cell population, c-kit pos cardiac cells were separated through CD45-positive or -negative sorting followed by c-kit pos sorting. The blood/endothelial lineage-committed (Lineage pos ) CD45 pos c-kit pos cardiac cells were compared to CD45 neg (Lineage neg /Lin neg ) c-kit pos cardiac cells for stemness and myogenic properties in vitro and in vivo. The majority (~90%) of the resident c-kit pos cardiac cells are blood/endothelial lineage-committed CD45 pos CD31 pos c-kit pos cells. In contrast, the Lin neg CD45 neg c-kit pos cardiac cell cohort, which represents ⩽10% of the total c-kit pos cells, contain all the cardiac cells with the properties of adult multipotent CSCs. These characteristics are absent from the c-kit neg and the blood/endothelial lineage-committed c-kit pos cardiac cells. Single Lin neg c-kit pos cell-derived clones, which represent only 1-2% of total c-kit pos myocardial cells, when stimulated with TGF-β/Wnt molecules, acquire full transcriptome and protein expression, sarcomere organisation, spontaneous contraction and electrophysiological properties of differentiated cardiomyocytes (CMs). Genetically tagged cloned progeny of one Lin neg c-kit pos cell when injected into the infarcted myocardium, results in significant regeneration of new CMs, arterioles and capillaries, derived from the injected cells. The CSC's myogenic regenerative capacity is dependent on commitment to the CM lineage through activation of the SMAD2 pathway. Such regeneration was not apparent when blood/endothelial lineage-committed c-kit pos cardiac cells were injected. Thus, among the cardiac c-kit pos cell cohort only a very small fraction has the phenotype and the differentiation/regenerative potential characteristics of true multipotent CSCs.

Competing Interests: Competing interests: None declared.

Death by hanging is asphyxiation when the body is suspended by means of a ligature. Most deaths by hanging are suicides, though occasionally they are accidental or a homicidal event. The characteristics of the hanging marks depend on the ligature used, the dynamics and on the node position with respect to the neck. When the crime scene is contaminated, the hanging mark must be checked with the type of suspension and ligatures used to establish how the hangings took place. We report on 20 cases (2013-2016) where the bodies were moved at or from the crime scene. We analysed the features of hanging marks, the tools of suspension and the ligatures employed in each case. Judicial inspections and an external examination were also carried out. Analysis of hanging marks enables the pathologist to clarify the manner of death and the type of hanging, and tools used especially where the crime scene has been contaminated and the body has been moved.

In adults, the most common cause of sudden death is coronary heart disease or defects in the cardiac conduction system; however, there are many cases of sudden death occurring from other causes such as fatal pulmonary thromboembolism. Several risk factors are recognized, including hospitalization, surgery, obesity, pregnancy, the use of oral contraceptives, traumatic fractures, and genetic conditions, which cause hypercoagulable states such as factor V Leiden mutations. Although many risk factors have been identified, the mortality rate is still high. An association between thyroid disease and coagulation disorders has previously been demonstrated. However, scientific literature does not yet agree on the association between thyroid diseases and pulmonary thromboembolism. Excessive thyroid hormones can determine an alteration in the hemostatic system through different mechanisms, which lead to a hypercoagulable state. In forensic literature, there are no reports of fatal thromboembolism in patients with thyroid disorders. We reported a case of a 41-year-old woman who died during sexual activity. The autopsy findings highlighted the presence of massive pulmonary embolism. Histopathological analysis showed structural anomalies of the thyroid gland. A retrospective analysis of her medical history and possible genetic alterations were performed.

Aims: To evaluate how often patients with moderate-to-severe or severe mitral regurgitation (MR) meet the anatomical criteria for MitraClip implant and to examine the role of transthoracic echocardiography (TTE) for this task., Methods and Results: From February to June 2015, all patients undergoing a TTE in nine Spanish hospitals were prospectively included. Patients with moderate-to-severe and severe mitral regurgitation were selected for analysis. Anatomical eligibility criteria for MitraClip were defined according to the EVEREST trial. A total of 39 855 consecutive TTE were reviewed, and 1403 patients with moderate-to-severe and severe MR were finally included. Primary MR was found in 779 patients (56%). Only in 74 patients (16%), all anatomical criteria for MitraClip could be assessed by TTE. Of these, 56% of patients had optimal valve morphology. Secondary MR was described in 361 patients (26%), and at least 249 of these (69%) had a high surgical risk. All five criteria for MitraClip were adequately assessed by TTE in 299 patients (83%). Of them, 118 patients (39%) had optimal valve morphology., Conclusions: A considerable proportion of patients have optimal mitral valve morphology for MitraClip. Moreover, TTE was particularly useful in determining whether or not the anatomical criteria for MitraClip implant were met in the majority of patients with secondary MR but in only a minority of those with primary MR., (© 2017, Wiley Periodicals, Inc.)

Competing Interests: Competing interests: None declared.

Venous disease, including varicose veins and chronic venous insufficiency, is one of the most common chronic medical conditions. Haemorrhage from rupture of varicose veins in the legs is rare and can lead to sudden death. Nevertheless, this condition is not included among the causes of sudden death. In this case, an 88-year-old man was found dead in a large pool of blood at home. Initially, investigators mistakenly assumed that it was a case of homicide. Bloodstain pattern analysis was performed. An external examination of the victim showed an ulcer on the left foot and evident varicose veins untreated on the lower limbs. The aim of this study is to emphasize the role of treatment of varicose veins in the prevention of adverse events such as sudden death from acute haemorrhage.

Three-dimensional (3D) transesophageal echocardiography (TEE) is the gold standard for mitral valve (MV) anatomic and functional evaluation. Currently, dedicated MV analysis software has limitations for its use in clinical practice. Thus, we tested here a complete and reproducible evaluation of a new fully automatic software to characterize MV anatomy in different forms of mitral regurgitation (MR) by 3D TEE.Sixty patients were included: 45 with more than moderate MR (28 organic MR [OMR] and 17 functional MR [FMR]) and 15 controls. All patients underwent TEE. 3D MV images obtained using 3D zoom were imported into the new software for automatic analysis. Different MV parameters were obtained and compared. Anatomic and dynamic differences between FMR and OMR were detected. A significant increase in systolic (859.75 vs 801.83 vs 607.78 mm; P = 0.002) and diastolic (1040.60 vs. 1217.83 and 859.74 mm; P < 0.001) annular sizes was observed in both OMR and FMR compared to that in controls. FMR had a reduced mitral annular contraction compared to degenerative cases of OMR and to controls (17.14% vs 32.78% and 29.89%; P = 0.007). Good reproducibility was demonstrated along with a short analysis time (mean 4.30 minutes).Annular characteristics and dynamics are abnormal in both FMR and OMR. Full 3D software analysis automatically calculates several significant parameters that provide a correct and complete assessment of anatomy and dynamic mitral annulus geometry and displacement in the 3D space. This analysis allows a better characterization of MR pathophysiology and could be useful in designing new devices for MR repair or replacement., Competing Interests: The authors have no conflicts of interest to disclose.

Aims: A specialized three-dimensional transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced; the system automatically configures a geometric model of the aortic root from the images obtained by 3D-TOE and performs quantitative analysis of these structures. The aim of this study was to compare the measurements of the aortic annulus (AA) obtained by the new model to that obtained by 3D-TOE and multidetector computed tomography (MDCT) in candidates to transcatheter aortic valve implantation (TAVI) and to assess the reproducibility of this new method., Methods and Results: We included 31 patients who underwent TAVI. The AA diameters and area were evaluated by the manual 3D-TOE method and by the automatic software. We showed an excellent correlation between the measurements obtained by both methods: intra-class correlation coefficient (ICC): 0.731 (0.508-0.862), r: 0.742 for AA diameter and ICC: 0.723 (0.662-0.923), r: 0.723 for the AA area, with no significant differences regardless of the method used. The interobserver variability was superior for the automatic measurements than for the manual ones. In a subgroup of 10 patients, we also found an excellent correlation between the automatic measurements and those obtained by MDCT, ICC: 0.941 (0.761-0.985), r: 0.901 for AA diameter and ICC: 0.853 (0.409-0.964), r: 0.744 for the AA area., Conclusion: The new automatic 3D-TOE software allows modelling and quantifying the aortic root from 3D-TOE data with high reproducibility. There is good correlation between the automated measurements and other 3D validated techniques. Our results support its use in clinical practice as an alternative to MDCT previous to TAVI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: 3D transesophageal echocardiography (TEE) is superior to 2D TEE in quantitative anatomic evaluation of the mitral valve (MV) but it shows limitations regarding automatic quantification. Here, we tested the inter-/intra-observer reproducibility of a novel full-automated software in the evaluation of MV anatomy compared to manual 3D assessment., Methods: Thirty-six out of 61 screened patients referred to our Cardiac Imaging Unit for TEE were retrospectively included. 3D TEE analysis was performed both manually and with the automated software by two independent operators. Mitral annular area, intercommissural distance, anterior leaflet length and posterior leaflet length were assessed., Results: A significant correlation between both methods was found for all variables: intercommissural diameter (r = 0.84, p < 0.01), mitral annular area (r = 0.94, p > 0, 01), anterior leaflet length (r = 0.83, p < 0.01) and posterior leaflet length (r = 0.67, p < 0.01). Interobserver variability assessed by the intraclass correlation coefficient was superior for the automatic software: intercommisural distance 0.997 vs. 0.76; mitral annular area 0.957 vs. 0.858; anterior leaflet length 0.963 vs. 0.734 and posterior leaflet length 0.936 vs. 0.838. Intraobserver variability was good for both methods with a better level of agreement with the automatic software., Conclusions: The novel 3D automated software is reproducible in MV anatomy assessment. The incorporation of this new tool in clinical MV assessment may improve patient selection and outcomes for MV interventions as well as patient diagnosis and prognosis stratification. Yet, high-quality 3D images are indispensable.

Human activities involving water may result in a crime scene. Typically, death may be due to natural causes, homicide, or mass disasters. Decomposition in water is a complex process where many factors may interplay. Human remains in water are subject to many potential interactions, depending upon the remains themselves, the type of water and the characteristics of the water. A number of studies are focused on the decomposition process of the corpse in water, on the identification of the post mortem submersion interval (PMSI) and on the diagnosis of drowning, but very few studies consider the fate of floating remains in any aquatic environment. The following case describes a corpse found on a shore of the Tyrrhenian Sea (South West of Italy, Calabria Region). The corpse and the soles of his shoes were colonized by the barnacle Lepas anatifera L. (Crustacea: Cirripedia: Pedunculata). The analyses of the barnacles present on the corpse aided in the evaluation of the floating time of the corpse which assisted in estimating the minimum time since death., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ingesting caustic substances represents a common event which may result in serious injuries of the gastrointestinal system. Severity of injury depends on the type of ingested substance: Caustic burns are more frequently associated with acid ingestion and their severity depends on type, concentration, time of exposure, and amount of the ingested substance. We report a case of phosphoric acid ingestion leading to death in a patient with depressive disorder. While reports ingestion of other acids and organophosphates can be found in the literature, there are no reports detailing a death due to phosphoric acid ingestion. We hope that presenting the findings in this case can aid death investigators in future cases that may involve ingestion of such a substance. After autopsy pH, phosphate and calcium ions concentration in the blood were analyzed. The cause of death was due to systemic effects: metabolic acidosis, hypophosphatemia, hypocalcemia, and hyperkalemia., (© 2014 American Academy of Forensic Sciences.)

This protocol describes the isolation of endogenous c-Kit (also known as CD117)-positive (c-Kit(+)), CD45-negative (CD45(-)) cardiac stem cells (eCSCs) from whole adult mouse and rat hearts. The heart is enzymatically digested via retrograde perfusion of the coronary circulation, resulting in rapid and extensive breakdown of the whole heart. Next, the tissue is mechanically dissociated further and cell fractions are separated by centrifugation. The c-Kit(+)CD45(-) eCSC population is isolated by magnetic-activated cell sorting technology and purity and cell numbers are assessed by flow cytometry. This process takes ∼4 h for mouse eCSCs or 4.5 h for rat eCSCs. We also describe how to characterize c-Kit(+)CD45(-) eCSCs. The c-Kit(+)CD45(-) eCSCs exhibit the defining characteristics of stem cells: they are self-renewing, clonogenic and multipotent. This protocol also describes how to differentiate eCSCs into three main cardiac lineages: functional, beating cardiomyocytes, smooth muscle, and endothelial cells. These processes take 17-20 d.

Management of a crime is the process of ensuring accurate and effective collection and preservation of physical evidence. Forensic botany can provide significant supporting evidences during criminal investigations. The aim of this study is to demonstrate the importance of forensic botany in the crime scene. We reported a case of a woman affected by dementia who had disappeared from nursing care and was found dead near the banks of a river that flowed under a railroad. Two possible ways of access to crime scene were identified and denominated "Path A" and "Path B." Both types of soil and plants were identified. Botanical survey was performed. Some samples of Xanthium Orientalis subsp. Italicum were identified. The fall of woman resulted in external injuries and vertebral fracture at autopsy. The botanical evidence is important when crime scene and autopsy findings are not sufficient to define the dynamics and the modality of death., (© 2014 American Academy of Forensic Sciences.)

Background: Diabetes mellitus (DM) has multifactorial detrimental effects on myocardial tissue. Recently, carbonic anhydrases (CAs) have been shown to play a major role in diabetic microangiopathy but their role in the diabetic cardiomyopathy is still unknown., Methods and Results: We obtained left ventricular samples from patients with DM type 2 (DM-T2) and nondiabetic (NDM) patients with postinfarct heart failure who were undergoing surgical coronary revascularization. Myocardial levels of CA-I and CA-II were 6- and 11-fold higher, respectively, in DM-T2 versus NDM patients. Elevated CA-I expression was mainly localized in the cardiac interstitium and endothelial cells. CA-I induced by high glucose levels hampers endothelial cell permeability and determines endothelial cell apoptosis in vitro. Accordingly, capillary density was significantly lower in the DM-T2 myocardial samples (mean±SE=2152±146 versus 4545±211/mm(2)). On the other hand, CA-II was mainly upregulated in cardiomyocytes. The latter was associated with sodium-hydrogen exchanger-1 hyperphosphorylation, exaggerated myocyte hypertrophy (cross-sectional area 565±34 versus 412±27 μm(2)), and apoptotic death (830±54 versus 470±34 per 10(6) myocytes) in DM-T2 versus NDM patients. CA-II is activated by high glucose levels and directly induces cardiomyocyte hypertrophy and death in vitro, which are prevented by sodium-hydrogen exchanger-1 inhibition. CA-II was shown to be a direct target for repression by microRNA-23b, which was downregulated in myocardial samples from DM-T2 patients. MicroRNA-23b is regulated by p38 mitogen-activated protein kinase, and it modulates high-glucose CA-II-dependent effects on cardiomyocyte survival in vitro., Conclusions: Myocardial CA activation is significantly elevated in human diabetic ischemic cardiomyopathy. These data may open new avenues for targeted treatment of diabetic heart failure.

Traffic accidents have increased in the last decade, pedestrians being the most affected group. At autopsy, it is evident that the most common cause of pedestrian death is central nervous system injury, followed by skull base fractures, internal bleeding, lower limb haemorrhage, skull vault fractures, cervical spinal cord injury and airway compromise. The attribution of accident responsibility can be realised through reconstruction of road accident dynamics, investigation of the scene, survey of the vehicle involved and examination of the victim(s). A case study concerning a car accident where both humans and pets were involved is reported here. Investigation and reconstruction of the crime scene were conducted by a team consisting of forensic pathologists and forensic veterinarians. At the scene investigation, the pedestrian and his dog were recovered on the side of the road. An autopsy and a necropsy were conducted on the man and the dog, respectively. In addition, a complete inspection of the sports utility vehicle (SUV) implicated in the road accident was conducted. The results of the autopsy and necropsy were compared and the information was used to reconstruct the collision. This unusual case was solved through the collaboration between forensic pathology and veterinary forensic medicine, emphasising the importance of this kind of co-operation to solve a crime scene concerning both humans and animals., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The epidemic of heart failure has stimulated interest in understanding cardiac regeneration. Evidence has been reported supporting regeneration via transplantation of multiple cell types, as well as replication of postmitotic cardiomyocytes. In addition, the adult myocardium harbors endogenous c-kit(pos) cardiac stem cells (eCSCs), whose relevance for regeneration is controversial. Here, using different rodent models of diffuse myocardial damage causing acute heart failure, we show that eCSCs restore cardiac function by regenerating lost cardiomyocytes. Ablation of the eCSC abolishes regeneration and functional recovery. The regenerative process is completely restored by replacing the ablated eCSCs with the progeny of one eCSC. eCSCs recovered from the host and recloned retain their regenerative potential in vivo and in vitro. After regeneration, selective suicide of these exogenous CSCs and their progeny abolishes regeneration, severely impairing ventricular performance. These data show that c-kit(pos) eCSCs are necessary and sufficient for the regeneration and repair of myocardial damage., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We report the case of a 70-year-old woman found dead in her apartment in the South of Italy in February 2011. The detailed data showed that the victim was affected by familiar-type paranoid schizophrenia. This finding was confirmed by the discovery of antipsychotic and tricyclic antidepressant drugs in the house and the deposition of her psychiatric therapist. Before the autopsy, a multislice computed tomography (MSCT) scanning of the thoracic and facial maxillo-cervical area was performed that has allowed anatomical identification and diagnosis of a mechanical obstruction as the cause of death. The autopsy has showed the presence of materials obstructing the trachea totally. Histological and toxicological investigations were carried out on the victim. The toxicological investigation has shown the presence of metabolites of tricyclic antidepressants and antipsychotics in the blood and urine. The histology showed the presence of foreign-origin materials (starch fibres) inside the pulmonary alveolus. The cause of death was asphyxia due to obstruction by food-origin material. In this case the radiological data have been compared with the autopsy and toxicological and histological data. The comparison of results has shown that MSCT scanning may aid in identification of occlusion and then in determination of the cause of death. In conclusion, MSCT scanning can be proposed in the cases of suspected asphyxia, as the screening procedure of first instance to produce preliminary information useful to rapidly develop the successive autopsy performance., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Rationale: MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown., Objective: The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo., Methods and Results: We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression., Conclusions: Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases.

For a long time the heart has been considered a terminally differentiated organ without any regenerative potential. The latter has been classically based on the terminally differentiated nature of cardiomyocytes and the absence of a pool of tissue-specific stem cells. This view has been radically changed due to the discovery of resident cardiac stem and progenitor cells in the adult mammalian heart. However, at minimum, 5 apparently different cardiac stem and/or progenitor cell types have been described so far. Thus, we have changed from a view of the heart as a static tissue to an organ with the highest number of tissue-specific stem cell populations. Most likely, the different putative adult cardiac stem and progenitor cells represent different developmental and/or physiological stages of a unique resident adult cardiac stem cell. Notably, it is not yet known the origin of all these cells. A better understanding of the origin, biology and physiology of the myocardial stem and progenitor cells will impact the development of regenerative medicine as an effective therapy for heart disease and failure.

cAMP inhibits proliferation in most cell types, triggering different and sometimes opposing molecular pathways. p85alpha (phosphatidylinositol 3-kinase regulatory subunit) is phosphorylated by cAMP/PKA in certain cell lineages, but its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are unknown. In the present study, we evaluated 1) the role of p85alpha in the integration of cAMP/PKA-dependent signaling on the regulation of VSMC and EC growth in vitro; and 2) the effects of PKA-modified p85alpha on neointimal hyperplasia and endothelial healing after balloon injury in vivo. Plasmid constructs carrying wild-type and PKA-modified p85alpha were employed in VSMCs and ECs in vitro and after balloon injury in rat carotid arteries in vivo. cAMP/PKA reduced VSMC proliferation through p85alpha phosphorylation. Transfected PKA-activated p85alpha binds p21ras, reducing ERK1/2 activation and VSMC proliferation in vitro. In contrast, EC proliferation inhibition by cAMP is independent from PKA modification of p85alpha and ERK1/2 inhibition; indeed, PKA-activated p85alpha did not inhibit per se ERK1/2 activation and proliferation in ECs in vitro. Interestingly, cAMP reduced both VSMC and EC apoptotic death through p85alpha phosphorylation. Accordingly, PKA-activated p85alpha triggered Akt activation, reducing both VSMC and EC apoptosis in vitro. Finally, compared with controls, vascular gene transfer of PKA-activated p85alpha significantly reduced neointimal formation after balloon injury in rats, without inhibiting endothelial regeneration of the injured arterial segment. In conclusions, PKA-activated p85alpha integrates cAMP/PKA signaling differently in VSMCs and ECs. By reducing neointimal hyperplasia without inhibiting endothelial regeneration, it exerts a protective effect against restenosis after balloon injury.