Extracellular vesicles in cardiomyopathies: A narrative review.

Extracellular vesicles (EVs) are membrane-bound particles released by all cells under physiological and pathological conditions. EVs constitute a potential tool to unravel cell-specific pathophysiological mechanisms at the root of disease states and retain the potential to act as biomarkers for cardiac diseases. By being able to carry bioactive cargo (such as proteins and miRNAs), EVs harness great potential as accessible "liquid biopsies", given their ability to reflect the state of their cell of origin. Cardiomyopathies encompass a variety of myocardial disorders associated with mechanical, functional and/or electric dysfunction. These diseases exhibit different phenotypes, including inappropriate ventricular hypertrophy, dilatation, scarring, fibro-fatty replacement, dysfunction, and may stem from multiple aetiologies, most often genetic. Thus, the aims of this narrative review are to summarize the current knowledge on EVs and cardiomyopathies (e.g., hypertrophic, dilated and arrhythmogenic), to elucidate the potential role of EVs in the paracrine cell-to-cell communication among cardiac tissue compartments, in aiding the diagnosis of the diverse subtypes of cardiomyopathies in a minimally invasive manner, and finally to address whether certain molecular and phenotypical characteristics of EVs may correlate with cardiomyopathy disease phenotype and severity.

Pancreas-sparing, ampulla-preserving duodenectomy for major duodenal (D1-D2) perforations.

BACKGROUND: Ideal surgical treatment for acute duodenal injuries should offer a definitive treatment, with low morbidity and mortality. It should be simple and easily reproducible by acute care surgeons in an emergency. Duodenal injury, due to major perforated or bleeding peptic ulcers or iatrogenic/traumatic perforation, represents a surgical challenge, with high morbidity and mortality. The aim was to review definitive surgery with pancreas-sparing, ampulla-preserving duodenectomy for these patients. METHODS: Pancreas-sparing, ampulla-preserving D1-D2 duodenectomy was used for patients presenting with major duodenal injuries over a 5-year interval. The ampulla was identified and preserved using a transcystic/transpapillary tube. The outcomes were recorded. RESULTS: Ten patients were treated with this technique; seven had perforated or bleeding peptic ulcers, two had iatrogenic perforations and one blunt abdominal trauma. Their mean age was 78 (range 65-84) years. Four patients were haemodynamically unstable. The location of the duodenal injury was always D1 and/or D2, above or in close proximity to the ampulla of Vater. The surgical approach was open in nine patients and laparoscopic in one. The mean duration of surgery was 264 (range 170-377) min. All patients were transferred to the ICU after surgery (mean ICU stay 4·4 (range 1-11) days), and the overall mean hospital stay was 17·8 (range 10-32) days. Six patients developed major postoperative complications: cardiorespiratory failure in five and gastrointestinal complications in four. Surgical reoperation was needed in one patient for postoperative necrotizing and bleeding pancreatitis. Two patients died from their complications. CONCLUSION: Pancreas-sparing, ampulla-preserving D1-D2 duodenectomy for emergency treatment of major duodenal perforations is feasible and associated with satisfactory outcomes.

Likely Transiting Exocomets Detected By Kepler.

We present the first good evidence for exocomet transits of a host star in continuum light in data from the Kepler mission. The Kepler star in question, KIC 3542116, is of spectral type F2V and is quite bright at Kp = 10. The transits have a distinct asymmetric shape with a steeper ingress and slower egress that can be ascribed to objects with a trailing dust tail passing over the stellar disk. There are three deeper transits with depths of ≃ 0.1% that last for about a day, and three that are several times more shallow and of shorter duration. The transits were found via an exhaustive visual search of the entire Kepler photometric data set, which we describe in some detail. We review the methods we use to validate the Kepler data showing the comet transits, and rule out instrumental artefacts as sources of the signals. We fit the transits with a simple dust-tail model, and find that a transverse comet speed of ∼35-50 km s-1 and a minimum amount of dust present in the tail of ∼ 1016 g are required to explain the larger transits. For a dust replenishment time of ∼10 days, and a comet lifetime of only ∼300 days, this implies a total cometary mass of ≳ 3 × 1017 g, or about the mass of Halley's comet. We also discuss the number of comets and orbital geometry that would be necessary to explain the six transits detected over the four years of Kepler prime-field observations. Finally, we also report the discovery of a single comet-shaped transit in KIC 11084727 with very similar transit and host-star properties.

The plasmatic and salivary levels of IL-1ß, IL-18 and IL-6 are associated to emotional difference during stress in young male.

Saliva collection is considered a non-invasive method to detect inflammatory markers in response to emotional states within natural social contexts. Numerous studies have prompted an important role of cytokines in modulating distinct aspects of social and emotional behavior. The aim of this study was to investigate the reliability of plasma and saliva as investigative tools for measure some inflammatory marker levels (CRP, IL-1ß, IL-18, and IL-6). At the same time, the relationships between these markers and emotional states in response to a socio-cognitive stress (Academic Exam, AE), were considered. It was demonstrated that the plasma and saliva concentrations of all immune-mediators analyzed were significantly related across the socio-cognitive stress. In addition, when there was a close correlation to AE, the anger state, the IL-1ß, the IL-18 salivary and plasmatic concentrations were significantly higher, while they decreased during the AE. On the other hand, the anxiety state and the IL-6 levels significantly increased throughout the AE. The IL-1ß and IL-6 were positively associated to the anger and the anxiety state, respectively. In conclusion, our data highlight that different immune markers are similarly detectable in plasma and saliva during socio-cognitive stress. Also, they could be related to different emotional responses.

Soft X-Ray Second Harmonic Generation as an Interfacial Probe.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Super-oxide anion production and antioxidant enzymatic activities associated with the executive functions in peripheral blood mononuclear cells of healthy adult samples.

Executive Functions (EFs) involve a set of high cognitive abilities impairment which have been successfully related to a redox omeostasis imbalance in several psychiatric disorders. Firstly, we aimed to investigate the relationship between executive functioning and some oxidative metabolism parameters in Peripheral Blood Mononuclear Cells (PBMCs) from healthy adult samples. The Brown Attention-Deficit Disorder Scales were administered to assess five specific facets of executive functioning. Total superoxide anion production, Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) activities were evaluated on proteins extracted from the PBMCs. We found significant positive correlations between superoxide anion production and the total score of the 'Brown' Scale and some of its clusters. The GPx and CAT activities were negatively associated with the total score and some clusters. In a linear regression analysis, these biological variables were indicated as the most salient predictors of the total score, explaining the 24% variance (adjusted R(2)=0.24, ANOVA, p<.001). This study provides novel evidence that Executive Functions have underpinnings in the oxidative metabolism, as ascertained in healthy subjects.

The SHP-1 expression is associated with cytokines and psychopathological status in unmedicated first episode schizophrenia patients.

BACKGROUND: Recent lines of research have boosted awareness of the immunological facets of schizophrenia. However, associations with protein tyrosine phosphatase regulators have never been reported. The aim of our study was to investigate the expression and promoter status methylation of phosphatase SHP-1, a key negative regulator of the inflammatory process, in Peripheral blood mononuclear cells (PBMCs) of Schizophrenic patients. METHODS: We enrolled fifty-four (28 men and 26 women) unmedicated first episode subjects (SC) who met DSM-IV and thirty-eight (22 men and 16 women) healthy controls (HC). The SC psychopathological status was assessed using the Positive and Negative Syndrome Scale. We evaluated SHP-1 expression by Quantitative Real-time PCR (qPCR) and Western blotting (WB) methods and promoter status methylation through PCR bisulfate. IKK/NFkB signaling was detected by WB, and medium and plasma levels of pro-inflammatory cytokines (IL-1ß, IL-2, and TNF-α) by the ELISA method. SHP-1 was silenced by treating cells with specific siRNA. RESULTS: We found a significantly lower level of SHP-1 gene expression in PBMCs from SC vs. HC, consistently with which the promoter region analyzed presented significant hypermethylation. Silencing of SHP-1 expression induced higher activation of IKK/NF-kB signaling and pro-inflammatory cytokine production in ex vivo PBMCs from both SC and HC. Linear regression among patients generated a model in which SHP-1 expression explained 30% of the clinical negative symptom variance (adjusted R(2)=0.30, ANOVA p<0.001). CONCLUSIONS: Our findings are the first to suggest that impairment of SHP-1 expression is involved in the physiopathology of schizophrenia, opening fruitful new avenues for ameliorating treatment at least of negative symptoms.

[Early diagnosis and prevention of renal disease: collaboration between nephrologists and general practitioners]. / Diagnosi precoce e prevenzione delle nefropatie: collaborazione integrata con i medici di medicina generale.

Our outpatient clinic activity has taught us that a working relationship between general practitioners (GPs) and nephrologists may improve the definition of the diagnostic-therapeutic course for the benefit of the patient. We have therefore contacted the 7 teams comprising 104 GPs and pediatricians working in the area of the Agnelli Hospital in Pinerolo (132,000 inhabitants in 1,404 square kilometers) to assess the possibility of improving and strengthening the collaboration between GPs and nephrologists. The starting point was a direct telephone link aimed at dealing with patients' kidney problems in real time, evaluating history and clinical data, establishing the best timing of treatment, and defining the diagnostic and therapeutic options. The initiative was welcomed at all team meetings and it stimulated further requests for collaboration. One of the main requests was for simple clinical guidelines to deal with the most frequent clinical nephrological issues. This is the program we are carrying out: 1) We have established consulting hours during which GPs can call nephrologists at the hospital to discuss the best diagnostic-therapeutic approach for individual kidney patients. 2) We have identified diseases of common interest (isolated urinary abnormalities; hypertension; nephrotoxicity; abnormal renal function; chronic renal failure; urinary infections; kidney stones). 3) We have planned to draw up clinical guidelines. 4) We will discuss each draft with the team of GPs. On the basis of the gathered suggestions, we will prepare a final version of the guidelines to be sent to the GPs and pediatricians of our area.

Stroke in young patients: etiopathogenesis and risk factors in different age classes.

The aim of our study was to evaluate the etiopathogenesis and the vascular risk factors in a consecutive series of patients with juvenile ischemic stroke. We enrolled 273 patients (158 males and 115 females), aged between 16 and 49 years, with ischemic cerebrovascular events (ICVE), including transient ischemic attack (TIA) or stroke, referred to our neurology ward between January 1994 and December 2001. Our protocol included medical history, cardiac and neurological examinations, assessment of risk factors and laboratory tests. The instrumental assessment included transthoracic echocardiography (70%), transesophageal echocardiography (60%), conventional angiography (30%), MR angiography (30%), cranial computed tomography (100%) and brain MRI (48%). The ICVE was a stroke in 60% of the cases, a reversible ischemic neurologic deficit in 14% and a TIA in 26%. Thirty-three patients were aged less than 29, 59 were aged between 30 and 39 and 181 between 40 and 49. The percentage of females was higher in patients aged less than 29 while males were prevalent in the 4th and 5th decade. The patients were subtyped according to etiopathogenesis. A large-vessel disease (LVD) was diagnosed in 43 patients (16% of the cases), mostly in patients aged more than 40 years (36 cases). A small-vessel disease (SVD) was found in 48 patients (17% of cases), mostly in patients aged more than 40 years (41 cases). A cardioembolic stroke (CE) was diagnosed in 66 patients (24% of the cases). In the majority of the cases, the cardiopathies were at low-uncertain embolic risk: patent foramen ovale (PFO, 39 cases, in 8 patients associated with an atrial septal aneurism), atrial septal aneurism (12 cases) and myxomatous mitral valve prolapse (3 cases). Stroke due to other causes was found in 51 patients (19% of the cases). Arterial dissection, more frequently involving the carotid region, was diagnosed in 35 patients. Coagulopathies and vasculitis were found in 5 and 6 patients, respectively. Stroke of unknown etiology was found in 65 patients (24% of the cases) with a homogeneous distribution among decades. Our study highlights the role of minor cardiac sources of embolism and arterial dissection in the etiology of juvenile ischemic stroke, whereas coagulopathies and vasculitis are less relevant. LVD and SVD were relevant only in the 5th decade.

Metaphors of a bodily mind.

Patients' metaphors in analysis may allow access to ineffable experiences. This is understandable, since the mind is a bodily mind, and language is a fully embodied function of this mind. That is, both are dependent for their existence upon the physical body. The ontogenic accumulation of perceived sensory impressions and affective processes far exceeds what can be put into words. Research in cognitive psychology suggests that the active mind functions in such a manner that later perceptions are organized by means of earlier ones. However, since the mind can know only its own representations, it inhabits two ever unknown realms: the external world itself, and the domain of internal unconscious processes that sustain the mind's functions. As a result, the world and the self we know are constructed by the mediation of our bodies. In language also, the active mode by which we perceive, process, and feel makes our understanding of words dependent on previous experience. The fact that the limbic system is activated immediately in the moment of processing experience means that all modalities of representation include an affective valuation. This inevitable processing of information through the mediation of affectively valued bodily perceptions gives the metaphorical function-the human capacity to organize experience and life in metaphoric ways-the ability to create linguistic metaphors that can capture and express otherwise inexpressible psychic experiences. This manner of understanding metaphor has implications for psychoanalytic technique.

First person personal pronouns and their psychic referents.

This paper presents a psychoanalytic description of the psychic referents for the personal pronouns I, me, myself. The referents are related to memorial processes of experiences of satisfaction is early bodily dialogues. Later interpersonal dialogues, bodily and verbal, factual or fantazised, add to the memories available as potential referents for the pronouns. The linguistically spoken pronoun has a narrower referential field because a speech act can only tap a limited number of memories. The 'I'/'me' of each spoken sentence is a selected libidinal and narcissistically organised self-perception at the service of an exchange with the interlocutor at hand, the specific 'you' of that linguistic act. The linguistic 'I' is a transient pronominal function linked to memories about oneself and others. It reveals in the selection of referential sources, libidinal and narcissistic regulatory functions in the service of satisfaction of wishes, defence, and modulation of self-esteem.

Freud's speech apparatus and spontaneous speech.

Freud's first book published in 1891 was a monograph entitled On Aphasia. In it he challenges the main authorities of the time by asserting that their manner of understanding aphasias is no longer tenable. Freud proves their theories wrong and presents his own conception of a speech apparatus. The apparatus is the foundation of his clinical and theoretical explanations about the speech function and its pathological manifestations. He built the model of an apparatus capable of explaining spontaneous speech, a function that the competing models of his contemporaries could not fully integrate. Freud's speech apparatus is the first of several models he created to facilitate the understanding of psychic functions. This paper is part of a series dedicated to an in-depth study of the earliest model which would provide the foundations for the understanding of its reappearance in Freud's later theories, and in particular in his analytic technique.

Respect in clinical practice.

Respect is naturally presumed to be a component of the therapeutic relationship. Therapists, however, need to go beyond the everyday understanding of respect and be prepared to provide a dimension that we do not expect to find in other human relations.