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Background: Diseases of the oral cavity (OC) with an infectious trigger such as caries and periodontal disease are extremely common in the general population and can also have effects at the cardiovascular level. The oral salivary flow, with its buffering capacity, is able to regulate the pH of the OC and, therefore, significantly contribute to the ecological balance of the microenvironment in which the oral microbiome (OM) develops. On the other side, when the quality/quantity of salivary flow is altered it is supposed the disruption of this balance with the potential increase in oral pathogens and triggered diseases. Among the endogenous substances able to exert a significant effect on the salivary flow and its characteristics, carnosine (Car), a dipeptide originally isolated in skeletal muscle, represents, thanks to the known buffering properties, a promising principle. Methods: We aimed this protocol to evaluate the quantitative/qualitative characteristics of the salivary flow in healthy volunteer subjects (n = 20) and in subjects suffering from common OC pathologies (n = 40), before and after 7 days of supplementation with SaliflussTM (Metis Healthcare srl, Milan, Italy), a Class I medical device on the market as 400 mg mucoadhesive oral tablets that has Car as the main ingredient. Discussion: Combining the characteristics of saliva with the OM and comparing them with OC pathologies, we expect to clarify their reciprocal relationship and, using quantitative proteomics techniques, to help clarify the mechanism of action of Car.

INTRODUCTION Spontaneous coronary artery dissection (SCAD) is an established cause of acute myocardial infarction (AMI), with an incidence in young women ranging from 22% to 43%. The increased use of coronary angiography contributed to better recognise this condition. Nonetheless, the presentation remains challenging mainly due to the atypical clinical onset. AIMS AND METHODS A very homogeneous case series of 10 young women (age 36 ± 9 years) admitted at our Institution over a period of 10-years with ST-elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) were analysed. All women had no congenital, coronary, cardiac and/or atherosclerotic disorders. The clinical and angiographic data were evaluated and correlated to the outcome that lasted 5 ± 5 years. RESULTS The clinical presentation was typical in 70% of cases and 30% of them developed ventricular arrhythmias and cardiogenic shock. An atypical presentation was documented in 30%. STEMI accounted for 70%, NSTEMI for 30%. Among the predisposing factors, pregnancy was related in 20%, connective tissue disorders in 30% and acute emotional stress associated to smoke habit in 50% of cases. On coronary angiogram all women were affected by distinctive pattern of non-atherosclerotic single vessel disease: LAD dissection (50% of cases with proximal localization), first obtuse marginal branch dissection in 3 cases, proximal RCA dissection in 1. Medical therapy was the first choice in 40%, while 60% were treated with PTCA-stent (multiple in 30%). The ejection fraction early after AMI was normal in 70%, mildly reduced in 1 case and moderately reduced ( CONCLUSION A high proportion of subjects presented with atypical challenging symptoms, while 30% were complicated with ventricular arrhythmias. This might be related to the high prevalence of proximal LAD dissection and anterior AMI in our subjects. An equal distribution of risk factors was recorded. No mortality events and no SCAD-recurrence were documented during follow up. Abstract P978 Figure. Image 1

Medical practice is increasingly coming under the guidance of statistical-mathematical models that are, undoubtedly, valuable tools but are also only a partial representation of reality. Indeed, given that statistics may be more or less adequate, a model is still a subjective interpretation of the researcher and is also influenced by the historical context in which it operates. From this opinion, I will provide a short historical excursus that retraces the advent of probabilistic medicine as a long process that has a beginning that should be sought in the discovery of the complexity of disease. By supporting the belonging of this evolution to the scientific domain it is also acknowledged that the underlying model can be imperfect or fallible and, therefore, confutable as any product of science. Indeed, it seems non-trivial here to recover these concepts, especially today where clinical decisions are entrusted to practical guidelines, which are a hybrid product resulting from the aggregation of multiple perspectives, including the probabilistic approach, to disease. Finally, before the advent of precision medicine, by limiting the use of guidelines to the original consultative context, an aged approach is supported, namely, a relationship with the individual patient.

Key Clinical Message Supraventricular arrhythmias can sometimes be “only” epiphenomena appearing during acute hypoxia, pneumonia, pulmonary embolism, and thrombosis. Indeed, atrial fibrillation is not rare in acute aortic dissection as it is estimated in about one half of patients and may be secondary to a perfusion deficit of the sinoatrial node artery.

Clinical studies/trials are experiments or observations on human subjects considered by the scientific community the most appropriate instrument to answer specific research questions on interventions on health outcomes. The time-line of the observations might be focused on a single time point or to follow time, backward or forward, in the so called, respectively, retrospective and prospective study design. Since the retrospective approach has been criticized for the possible sources of errors due to bias and confounding, we aimed this study to assess if there is a prevalence of retrospective vs. prospective design in the clinical studies/trials by querying MEDLINE. Our results on a sample of 1,438,872 studies/trials, (yrs 1960–2017), support a prevalence of retrospective, respectively 55% vs. 45%. To explain this result, a random sub-sample of studies where the country of origin was reported (n = 1,576) was categorized in high and low-income based onthe nominal Gross Domestic Product (GDP) and matched with the topic of the research. As expected, the absolute majority of studies/trials are carried on by high-income countries, respectively 86% vs. 14%; even if a slight prevalence of retrospective was recorded in both income groups, for the most part prospective studies are carried out by high-GDP countries, 85% vs. 15%. Finally, the differences in the design of the study are understandable when considering the topic of the research.

A standard meal is a stimulus that produces a response that consists in the redistribution of blood flow to the splanchnic district, potentially, affecting systemic blood pressure, this phenomenon was studied in animal models and in critic patient. Here we report a case of a diabetic hypertensive-in-treatment woman where two significant blood pressure peaks were recorded, during lunch and dinner, over an optimal 24/h blood pressure control. In the absence of previous normal reference values in the literature, we retrieved a series of n=10 age and sex matched subjects diagnosed normotensive on the mean of 24/h Ambulatory Blood Pressure Monitoring. We finally present our considerations on the normal response to a standard meal compared to what was found in the literature and in the present case, where an impaired control of resistance is hypothesised, and on the possible mechanisms supporting.

Clinical studies/trials are experiments or observations on human subjects considered by the scientific community the most appropriate instrument to answer specific research questions on interventions on health outcomes. The time-line of the observations might be focused on a single time point or to follow time, backward or forward, in the so called, respectively, retrospective and prospective study design. Since the retrospective approach has been criticized for the possible sources of errors due to bias and confounding, we aimed this study to assess if there is a prevalence of retrospective vs prospective design in the clinical studies/trials by querying MEDLINE. Our results on a sample of 1,438,872 studies/trials, (yrs 1960-2017), support a prevalence of retrospective, respectively 55% vs 45%. To explain this result, arandom sub-sample of studies where the country of origin was reported (n=1576) was categorized in high and low-income based onthe nominal Gross Domestic Product (GDP) and matched with the topic of the research. As expected, the absolute majority of studies/trials are carried on by high-income countries, respectively 86% vs 14%; even if a slight prevalence of retrospective was recorded in both income groups, nonetheless the most part of prospective studies are carried out by high-GDP countries, 85% vs 15%. Finally the differences in the design of the study are understandable when considering the topic of the research.

Background The simultaneous measurement of multiple cytokines in parallel by using multiplex proteome arrays (MPA) is of great interest to understanding the inflammatory response following myocardial infarction; however, since cytokines are pleiotropic and redundant, increase of information throughput (IT) attained by measuring multiple cytokines remain to be determined. We aimed this study to assess the IT of an MPA system designed to assess 8 cytokines – commercially available at the time of the study – serum levels, before (control state) and after experimental myocardial cryoinjury (activated state) in rats. Methods By assuming that redundant information do not generally increase the IT, we derived Entropy ( H ) and Redundancy ( R ) of information by using formulas of Shannon modified accordingly, where a high IT (high H and low R ) corresponds to a low level of correlation between cytokines and vice versa for a low IT. The maximum theoretical level of IT and the contribution of each cytokine were also estimated. Results In control state, no significant correlations were found between cytokines showing high IT; on the contrary, in activated state, several significant correlations were found supporting a complex cross-talk pattern between cytokines with low IT. Using as reference the maximum theoretical level of IT, in activated state, H was reduced of 67.0% and R was increased of 77.4% supporting a reduction of IT. Furthermore, the contribution of individual cytokines to H value of MPA was variable: in control state, IL-2 gave the most contribution to H value, conversely during activated state IL-10 gave most contribution. Finally during activated state, IL-1β was the only cytokine strongly correlated with values of all other cytokines, suggesting a crucial role in the inflammatory cascade. Conclusions Paradoxically, by analyzing an MPA system designed for redundant analytes such as cytokines, translating the Shannon's information theory from the field of communication to biology, the IT system in our model deteriorates during the activation state by increasing its redundancy, showing maximum value of entropy in the control conditions. Finally, the study of the mutual interdependence between cytokines by the contribution to the IT may allow formulating alternative models to describe the inflammatory cascade after myocardial infarction.

Heart rate variability (HRV) is the temporal beat-to-beat variation in successive RR intervals on an electrocardiographic (ECG) recording and it reflects the regulation of the heart rate (HR) by the autonomic nervous system (ANS). HRV analysis is a noninvasive tool for the assessment of autonomic function that gained momentum in the late 1980s when its clinical relevance as a predictor of mortality was established by a milestone study by Kleiger et al. in patients with postacute myocardial infarction. In the last few decades, the increasing availability of commercial ECG devices offering HRV analysis has made HRV a favorite marker for risk stratification in the setting of cardiovascular disease. The rapid aging of the world population and the growing popularity of HRV have also fueled interest for the prognostic value of HRV in the elderly, outside a specific cardiological context. However, the discussion of HRV measures in the elderly is still very much centered on the rather reductionistic model of sympathovagal balance, with the orthosympathetic and parasympathetic limbs of the ANS exercising opposing effects on the heart via autonomic tone. The expanding application of nonlinear dynamics to medicine has brought to the forefront the notion of system complexity, embedded in the mathematical concepts of chaos theory and fractals, and provides an opportunity to suggest a broader interpretation for the prognostic significance of HRV, especially in the elderly. Although the use of novel indices of HRV may be hampered by practical issues, a more holistic approach to HRV may still be safeguarded if traditional time- and frequency-domain measures are viewed in terms of autonomic modulation. This review focuses on HRV in geriatric populations. It considers studies on the prognostic value of HRV in elderly subjects, discussing the potential confounding effect of erratic rhythm, and concentrates on the conceptual distinction between autonomic tone and autonomic modulation. It also briefly addresses the question of the practicality of ECG recordings and identifies a promising area for future research in the effects of common noncardioactive drugs on HRV.

Erectile dysfunction (ED) is often associated with cardiovascular disease (CVD) and the risk of sildenafil-induced orthostatic hypotension (OH) in subjects with CVD is a matter of concern. We describe our experience in using the tilt test (TT) with continuous plethysmography to evaluate the occurrence of OH in patients with CVD and ED after a test dose of sildenafil. When sildenafil was added on top of their usual pharmacological treatment two patients out of 32 (6.2%) developed asymptomatic OH, with a maximum blood pressure fall of 40/20 mm Hg. The low prevalence and modest clinical relevance of OH in our high-risk population coupled with the known high sensitivity and reproducibility of the TT seem to suggest that sildenafil is haemodynamically safer than is generally believed even when added on top of vasoactive treatment. These findings should be put into perspective against the growing wealth of evidence that PDE5 inhibitors may have therapeutic potential for a number of CV conditions.

Myocardial fibrosis is commonly observed in left ventricular (LV) hypertrophied heart during Arterial Hypertension. This pathological change coupled with vascular stiffening with aging and diabetes may reduce the cardiovascular system elasticity contributing to the functional impairment. Both the LV adaptive response to the increasing blood pressure and the oxidative damage contribute to myocardial fibrosis; in particular, reactive oxygen species (ROS) induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which in turn react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links. The vascular wall matrix then becomes less distensible, as the formation of the adducts induces greater capacity in collagen to resist normal turnover. Therefore, monitoring cardiac fibrosis and markers of collagen synthesis, degradation and non-enzymatic cross-linking and the use of drugs that revert collagen accumulation and/or prevent/repair non-enzymatic cross-linking might represent a novel opportunity to alter the natural history of hypertensive heart disease. Recent evidences have suggested to target the excess of collagen cross-links; initial evidence seems to show that fibrosis is not affected to the same degree by all anti-hypertensive agents. ACEI and ARBs appear particularly effective. Finally, agents acting as cross-link breakers on AGEs or preventing AGEs formation or affecting the TTG activity are emerging.

Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n=7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n=8); treated with TNBS enema plus oral CysN (TNBS-CysN group; n=8); treated with CysN (CysN group; n=7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-α (TNF-α) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS-CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43±0.78 vs 3.28±0.95, microscopic score 6.62±12.01 vs 19.25±6.04, P

Uncomplicated diverticular disease is a common condition in patients older than 50 years. Symptoms are aspecific and overlapping with those of irritable bowel syndrome. Nowadays, patients are often treated with antinflammatory drugs (5-aminosalicilic acid). Our purpose was to evaluate the presence of inflammation in the colonic mucosa of patients with symptomatic uncomplicated diverticular disease compared with subjects without diverticula. Endoscopic biopsies of colon from 10 patients with symptomatic uncomplicated diverticular disease and 10 from subjects without diverticula (controls) were taken. Specimens were homogenised and IL2, IL4, IL5, IL8, IL10, IL12p70, IL13, IFN gamma, TNF alfa (searchlight multiplex technique), TGF beta, transglutaminase type 2 and caspase 9 were measured. Histochemistry for transglutaminase type 2 and TUNEL were performed on the histological sections, in addition to morphologic evaluation, as markers of tissue remodelling and apoptosis. For statistical analysis Student’s t test and Spearman correlation test were used. No histological differences were detected between the patients with an uncomplicated diverticular disease and controls. Mean values of mucosal cytokines and of the other tested parameters did not show statistically significant differences between patients with uncomplicated diverticular disease and controls. Even if based on a small number of patients, the study demonstrates the absence of inflammation in the mucosa of subjects affected by uncomplicated diverticular disease.

Cardiac performance after myocardial infarction is compromised by ventricular remodeling, which represents a major cause of late infarct-related chronic heart failure and death. In recent years, the scientists' interest has focused on the hypothesis that the administration of bone marrow progenitors, following myocardial infarction, could ameliorate left ventricular remodeling by continuing to differentiate along the haematopoietic lineage. This approach has been developed minding to the consolidated use of transfusions to restore lost or depleted blood components and, therefore, as an enriched dose of various progenitors, generally autologous, injected peripherally or directly in the infarcted area. Since the safety of this therapy was not yet established, for ethical reasons pioneering researchers involved in these studies used animal models as surrogate of the human biologic system. Herein this hypothesis of therapy resulted in an increased use of living animals and in the reappraisal of models of myocardial damage with limited discussion on the theoretical basis of animal models applied to cell-based therapies. Recently, the European Union and its commission for surveillance of laboratory animals advanced a new proposal to restrict the use of living animals. This review will focus on the history of models utilization in biomedicine, with particular attention to animal models, and delineate an operative comparison between the two best known models of myocardial injury, namely coronary ligation and cryodamage, in the perspective of adult stem cell research applied to cardiovascular regenerative medicine.

This study investigates the effects of surgery on collagen turnover in patients affected by Crohn's disease (CD).Fifteen patients affected by active CD, assessed according to the Crohn's disease activity index, and confirmed by histology, with different pharmacological treatments, were enrolled in the study. N-Terminal propeptide of type III collagen was assessed on peripheral blood before and 6 months after surgery, as an index of collagen turnover. A control group of 15 healthy age- and sex-matched subjects was also studied.In CD patients peripheral N-terminal propeptide of type III collagen serum levels were significantly higher than in controls before surgery (5.0 +/- 1.8 vs 2.7 +/- 0.7 microg/l, respectively; p = 0.0001). Six months after these values were significantly reduced (from 5.0 +/- 1.8 to 3.1 +/- 0.8 microg/l; p = 0.003). Independently on the pretreatment regimen and the duration of the disease, an improvement in the patients' symptoms was observed.The surgical resection of the affected intestinal segment in CD patients seems to be able to break down the collagen synthesis processes. Peripheral N-terminal propeptide of type III collagen could be seen as an additive marker to clinical and endoscopic observations after surgery.

Background Patients with primary multiple malignancies are progressively increasing due to prolonged survival of cancer patients and to the advances in diagnostic techniques and therapeutic options. Case presentation Here we present a 66 year-old caucasian patient with four synchronous primary malignant tumors affecting the lung, oropharynx, large bowel and prostate gland, respectively, treated with multidisciplinary approach. Conclusions The increased incidence of multiple malignant tumors is a real challenge to the clinician and clinical attention should be made to avoid a misdiagnosis. In addition an early diagnosis is essential to achieve a radical treatment. We believe that the treatment modality should be carefully made and tailored on the individual patient suffering from this disease.

It's time to rethink prevention as a strategy to fight diseases? In this opinion I'll try to question preventive medicine as a strategy starting from the evidences on the randomness of disease, as suggested by recent and very questioned data on variation in cancer risk among different tissues. To understand the scope of this refutation we must remember that the preventive strategy was developed since the introduction of the concept of risk factor, that date back to the Framingham Heart Study (FHS) started in 1948. Indeed, prior to the FHS, doctors were still engaged in the study of causation by following the established paradigm of aetiology, and had not yet focused on the concept of multifactorial diseases and prevention or prophylaxis of risk factors was not yet a paradigm in medicine. After having metabolised these new concepts and made prevention of risk factors the main strategy to fight multifactorial diseases for years, today, in a Western world that is aging, we are facing a new challenge since prevention seems to be no longer enough to cope with diseases such as cancer and, possibly, we need new strategies that we still have not. And this why? Possibly because the randomness appears ever more like the engine that drives the physical universe even if, for living organisms, we must admit several deterministic or, at least, very reproducible events since they are able to actively interact with the environment.

In normal myocardium, myocytes represent only one-third of all cells, with the remaining two-thirds including fibroblasts and small cellular populations. While several weeks post partum the myocyte count stops increasing, the connective tissue cell count does not. In the early phases of arterial hypertension, adaptive left ventricular (LV) hypertrophy (LVH) is characterised by the growth of cardiac myocytes, which may or may not be accompanied by other alterations in tissue structure. In hypertensive heart disease, however, complex changes in myocardial composition occur, with a disproportionate involvement of noncardiomyocyte cells accounting for a pathological remodelling of tissue structure (pathological hypertrophy). Myocardial fibrosis is the result of both haemodynamic and nonhaemodynamic factors playing a synergistic role and reflects the loss of the physiological reciprocal regulation between stimulatory and inhibitory factors acting on the turnover of fibrillar collagen. Cardiac biopsy is the gold standard for assessing myocardial fibrosis; in the last decades different non-invasive approaches have been developed and validated to detect and follow-up cardiac fibrosis, including biochemical markers of collagen synthesis and degradation, cardiac hormones and ultrasonographic procedures. Due to the clinical implications of myocardial fibrosis and pathological LVH, it is of great interest to ascertain the effect of antihypertensive agents on cardiac structure: the optimal treatment of hypertensive patients should target a parallel decrease in cardiac mass and fibrosis. Preliminary evidence suggests that not all antihypertensive drugs affect fibrosis to the same extent: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) appear particularly effective, in contrast to β-blockers and diuretics. Finally, the impact of fibrosis and its regression on subsequent cardiovascular events when compared with LV mass and its reduction remain to be investigated.

Objective: Inflammatory bowel diseases are characterized by disorders of immunity, thrombosis of large vessels, and microthrombosis of mucosal vessels. The expression of endothelial protein C receptor (EPCR) and thrombomodulin-two receptors of the protein C pathway involved in thrombin scavenging and inflammation-was studied in intestinal resection specimens or mucosal biopsies from patients with inflammatory bowel disease and from controls. The soluble forms of the receptors in plasma were measured. Data Source: This study involved patients from two large university hospitals. After surgery or biopsy, tissue samples were either frozen or fixed in formalin and embedded in paraffin. Sections for immunohistochemistry examination were cut and tested with the specific antibodies to EPCR and thrombomodulin. RNA was extracted from frozen tissue for amplification via reverse-transcriptase polymerase chain reaction. Normal intestinal and diverticulitis tissue was used as a control. Resection samples from 36 patients with ulcerative colitis, 38 with Crohn's disease, 38 with colonic cancer, and 32 with diverticulitis were studied by immunohistochemistry, and frozen sections from the same patients were studied by immunofluorescence. Twelve biopsy specimens of adjacent intestinal areas from six patients with inflammatory bowel disease were included in the study for reverse-transcriptase polymerase chain reaction. Soluble receptors were measured in the plasma of 52 inflammatory bowel disease patients and 52 controls. Data Summary: EPCR and thrombomodulin were expressed on the mucosal endothelium of controls, and the intensity of the signal decreased in inflammatory bowel disease patients. EPCR was expressed by dendritic-like cells in controls, which also stained positive for CD21. The EPCR + /CD21 + dendritic-like cells were not as commonly observed in sections from ulcerative colitis patients as they were in sections from control patients (12.0 ± 3.6 cells per high-power field vs. 23.8 ± 10.4 cells per high-power field, p = .03), and this decrease was less evident in sections from Crohn's disease patients. Levels of messenger RNA for EPCR paralleled protein expression. Soluble thrombomodulin and EPCR levels were both higher in patients than in controls: 41.5 vs. 26.0 ng/mL (p

BACKGROUND: The selective homing of peripherally injected marrow MNCs (MMNCs) has recently been demonstrated in a model of cryodamaged heart. However, the mechanism underlying this phenomenon is still unknown. In the hypothesis that this process is related to the necrotic area extension, the infarcted area was correlated with the number of homed MMNCs in a model of experimental cryodamaged heart. STUDY DESIGN AND METHODS: A total of 12 donor and 12 recipient inbred isogenic adult (4 weeks old) Fisher rats were used to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by cryoinjury. MMNCs were purified, labeled with PKH26 (a red fluorescent cell dye), and infused 7 days after the injury through the femoral vein of recipient rats. One week after peripheral administration, the number of homed MMNCs was assessed and the infarct size was correlated with the number of cells present in the target. RESULTS: Labeled cells were found only in the injured myocardium of the treated animals (n = 6), where a mean of 12 ± 3 PKH26+ cells per section examined were found; a significant correlation was found between the infarct size and the estimated number of cells (p = 0.008) CONCLUSION: These data indicate that the homing of MMNCs is related to the extent of the myocardial injury, suggesting that cellular therapy for regeneration of damaged myocardium should be individualized by taking into consideration the extension of the area to repair.

OBJECTIVE Ultrasonic tissue characterization of epi-aortic vessels may be useful to define the composition of atherosclerotic plaques. Videodensitometry provides a histogram representing the frequency distribution of gray levels corresponding to different compositions of the carotid wall. However, lack of standardization limits the clinical application of this technique. In the present study, the echoreflectivity (ER) pattern of atherosclerotic plaques in vivo was compared with their histological pattern after surgical removal, and the reproducibility of measurement was tested. DESIGN AND METHODS We studied 19 hypertensive patients with a carotid artery stenosis >or= 70%, eligible for carotid thromboendarterectomy (TEA). Before TEA, all patients underwent standard high-resolution B-mode carotid ultrasound. ER parameters (mean gray level, broad band, skewness, and kurtosis) were obtained in a region of interest selected along the whole plaque, between the intima-blood and the media-adventitia interfaces. The plaques removed during TEA were examined by a histologist and classified into three groups on the basis of fibrous tissue (FT) content: lipidic (FT 50%). Discriminant function analysis was used to evaluate classification efficacy of different histological groups based on ER parameters. RESULTS Histologically, five lesions were classified as lipidic, six as fibrolipidic and eight as fibrous. Analysis of variance showed significant between group differences in all ER parameters. The combined use of all ER parameters provided correct classification of plaques in 94.73% of cases (P < 0.0001), improving the classification made using single parameters. Intra-observer and inter-observer variabilities (Bland-Altman method) of mean gray level measurements were small. CONCLUSIONS Videodensitometry can discriminate between tissue composition of carotid lesions and complement the quantitative assessment of intima-media thickness by additionally providing a well-reproducible semiquantitative evaluation of vascular wall constituents.

Here we report the case of an 86-year-old woman with advanced dementia addressed to our service for routinary ECG Holter Monitoring (EHM) for bradycardia in AV block type I. Several day-time episodes of fall-asleep while sitting had been previously reported by the nurse and generally attributed to the dementia itself, without taking into consideration the hypothesis of an AV block. The EHM reading reported several and often subsequent pauses (561), many of them critical, the longest lasting 15,9 s with no changes in clinical condition of the patient. The results of the EHM were reported to the physicians in charge for the patient and subsequently the woman was referred to the arrhythmology unit for pace-maker device implantation. Generalizing our experience, we suggest that advanced dementia, often associated with episodes of fall-asleep, could mask a conduction disturbance causing critical pauses with syncope; therefore we suggest screening those patients for possible arrhythmic disorders. Finally, we remark that in our patient the pauses weren’t associated with a worsening of the patient as seen in the follow-up, and this fact supports the hypothesis that vascular dementia could increase cerebral ischaemic tolerance.

Objective Acromegaly is frequently associated with an increase in left ventricular mass, even in the absence of systemic hypertension. Pathological studies on acromegalic hearts have shown an extensive interstitial fibrosis, suggesting the existence of a specific acromegalic cardiomyopathy. The aim of this study was to assess left ventricular wall structure in acromegaly by ultrasonic tissue characterization. Design and methods We studied 10 untreated acromegalic patients and 10 age-matched healthy control subjects. The echo patterns of two-dimensional long-axis end-diastolic echocardiograms were assessed by colour-scale analysis of the interventricular septum, with estimates of the mean colour scale value, the broad band (Bb) and the derived collagen volume fraction (dCVF). We also measured electrocardiographic QT interval dispersion (QTd) as a marker of dyshomogeneous ventricular repolarization. Results Seven patients had left ventricular hypertrophy according to the sex-independent criteria; of these, two had arterial hypertension. None of our patients had echocardiographic evidence of diastolic or systolic dysfunction. All patients showed significantly increased myocardial echoreflectivity (Bb = 106.4 ± 12.1 versus 79.3 ± 6.5; dCVF% = 2.78 ± 0.53 versus 1.58 ± 0.29; P

Echocardiographic image texture has been demonstrated to reflect the physical properties of the tissue under examination. To evaluate the role of collagen in determining the echo pattern of the left ventricular wall, we studied nine hypertensive patients with left ventricular hypertrophy (left ventricular mass index > 125 gm/m2) and biopsy-proven different degrees of myocardial fibrosis by analyzing the echocardiographic examinations performed before the biopsy. Myocardial tissue was sampled under fluoroscopy and two-dimensional echo guidance in the interventricular septum. Collagen volume fraction (CVF; normal range up to 2%) was taken as an index of fibrosis. The echo patterns were assessed by analyzing standard two-dimensional parasternal long-axis echocardiograms recorded on videotape. Images were color-coded at 256 levels (0 = yellow, 256 = black) and digitized off-line onto a personal computer. The region of analysis was set using a selection tool (20 x 10 mm) in the general area of septum where the specimen was taken. For each selection a color-level histogram, representing the frequency distribution, was derived with estimates of the average pixel intensity (mCS), skewness (SK), kurtosis (K), and the broad band (Bb) of the echoes about the distribution. Echo-derived parameters in each patient were compared with corresponding CVF values. CVF was out of range in all patients, ranging from 2.6% to 7.6% (mean 4.3% +/- 1.6%). No correlation was found between CVF and mCS, whereas a significant correlation was found at end diastole between CVF and the parameters describing histogram morphology, respectively, SK (r = 0.73), K (r = 0.69), Bb (r = 0.72). These findings for the first time demonstrate in vivo in hypertensive patients with left ventricular hypertrophy an agreement between echo amplitude and histologically assessed collagen volume. Thus in our studied patients collagen content appears to be the major determinant of regional echo intensity, its increase resulting in a significant and progressive wider asymmetrical left shift (yellow) of the color histogram.

The origin and the meaning of life on the earth was traditionally attributed to an intelligent creator as an independent act until 1859 when Charles Darwin compiled the book The Origin of Species (Darwin, 1859). In this book Darwin introduced the theory of evolution by natural selection (Figure 1, central panel) opening a new perspective to read what looks like the largest experiment on earth called biological life. This new perspective has proposed a reversal of the traditional view where the intelligence is placed above the experiment by introducing the concept of transformation or evolution (Dennett, 2009). In this upside down view intelligence is not excluded but, rather, is within the experiment and drives the so called "struggle for life" in a dynamic planet where habitats are continuously destroyed and created.

Heart rate variability (HRV) is the temporal beat-to-beat variation in successive RR intervals on an electrocardiographic (ECG) recording and it reflects the regulation of the heart rate (HR) by the autonomic nervous system (ANS). HRV analysis is a noninvasive tool for the assessment of autonomic function that gained momentum in the late 1980s when its clinical relevance as a predictor of mortality was established by a milestone study by Kleiger et al. in patients with postacute myocardial infarction. In the last few decades, the increasing availability of commercial ECG devices offering HRV analysis has made HRV a favorite marker for risk stratification in the setting of cardiovascular disease. The rapid aging of the world population and the growing popularity of HRV have also fueled interest for the prognostic value of HRV in the elderly, outside a specific cardiological context. However, the discussion of HRV measures in the elderly is still very much centered on the rather reductionistic model of sympathovagal balance, with the orthosympathetic and parasympathetic limbs of the ANS exercising opposing effects on the heart via autonomic tone. The expanding application of nonlinear dynamics to medicine has brought to the forefront the notion of system complexity, embedded in the mathematical concepts of chaos theory and fractals, and provides an opportunity to suggest a broader interpretation for the prognostic significance of HRV, especially in the elderly. Although the use of novel indices of HRV may be hampered by practical issues, a more holistic approach to HRV may still be safeguarded if traditional time- and frequency-domain measures are viewed in terms of autonomic modulation. This review focuses on HRV in geriatric populations. It considers studies on the prognostic value of HRV in elderly subjects, discussing the potential confounding effect of erratic rhythm, and concentrates on the conceptual distinction between autonomic tone and autonomic modulation. It also briefly addresses the question of the practicality of ECG recordings and identifies a promising area for future research in the effects of common noncardioactive drugs on HRV.

The normal cell is confined by its genetic program to a rather narrow range of morphofunctional characteristics within which it is nevertheless able to handle normal physiological demands (Kumar et al., 2011). A single cell, placed in an appropriate environment, contains, enclosed in its genome, sufficient information to generate a variety of differentiated cell types, whose spatial and temporal dynamics interact to form detailed morphological patterns (Geard and Wiles, 2005). Similarly, in multicellular organisms, it is the genetic program that establishes networks basics -including differentiation, functional hierarchy and interaction patternswith each level in the system representing an increase in organizational complexity. Indeed the emergence from a single or few stem cells of multicellular organisms with a complex organization must be seen as a necessity in evolution since it alone can ensure an optimal use of resources (Furusawa and Kaneko, 2000). From such evolutionary perspective, the development of a cardiovascular system in complex organisms fulfills the need for transport of nourishment, oxygen and metabolic waste as well as the need for communication between distant districts. All closed biological systems facing the external environment, whatever their level of complexity, are characterized by the ability to maintain a stable, constant condition by regulating themselves and the internal environment. In the early 19th century Cannon (Cannon, 1926) defined this property “homeostasis”, from the Greek: ὅμοιο┪, homoios, "similar" and ┫┬ά┫ι┪, stasis, "standing still". This condition of relative equilibrium grants the biological system a certain degree of independence from the environment and enables what we call life. Any change, either decremental or incremental, in the internal/external environment of the cell/organism such that it requires an active response from the cell/organism can be termed demand. In the case of complex organisms demands are met by the functional reserve of the cell/tissue/organ. The functional reserve is involved in the process of adaptation by which a cell/organism acquires morphofunctional features that allow it to better fit in with the changed environment and thus attain a new equilibrium (Figure 1). Adaptation is driven by the genetic program, via the activation of appropriate subsets of genes, and is influenced by the qualitative and quantitative characteristics of the demand such as its nature, intensity and duration. Adaptation can be considered to include both plasticity and adaptability. Plasticity is

The aim of this paper is to focus attention on complex cases of lung disease that may benefit from being managed outside formal guidelines. A 52 year-old man who had previously undergone a laryngectomy for squamous cell carcinoma, presented with a 1.2 cm nodule in the right upper pulmonary lobe. Three months later a new CT scan found that the nodule had slightly increased in size and also detected two new smaller nodules in the middle lobe. A PET/CT scan showed metabolic hyperactivity of all nodules. Since needle aspiration of the upper one revealed malignant cells, the patient was considered to be suffering from metastatic cancer and started on chemotherapy. At follow-up both CT and PET scans found a significant reduction in volume and activity of the lower nodules but no change in the upper one. At diagnostic thoracoscopy, histology demonstrated that the upper nodule was an adenocarcinoma while the lower ones were inflammatory. An upper lobectomy and systematic nodal dissection were therefore performed. Histology established a diagnosis of upper pulmonary adenocarcinoma and sarcoidosis. Our report suggests that in complicated oncologic cases in which non-invasive diagnostic tools yield incongruous results surgery should be considered without delay.

Tight junctions play a pivotal role in maintaining the integrity of the intestinal barrier. Their alteration is involved in the pathogenesis of celiac disease. Our aim was to investigate the gliadin effect on the tight junction proteins in an in vitro three-dimensional cell culture model through imaging analyses. Lovo multicellular spheroids were treated with enzymatically digested (PT) gliadin 500 μg/mL and its effect on actin, occludin and zonula occludens-1, was evaluated by means of confocal laser microscopy, transmission electron microscopy and image capture analysis. Compared to untreated spheroids, PT-gliadin-treated ones showed enlargement of the paracellular spaces (9.0±6.9 vs. 6.2±1.7 nm, p

The purpose of this experiment was to study the impact of simulated microgravity and of chronic removal of hydrostatic pressure gradients on blood pressure maturation and body growth in rats. A special device was developed in our laboratory to transfer prolonged "dry" water immersion (a technique that has been used for training astronauts under hypogravic conditions) to six Sprague-Dawley test rats (immersion-G group). The time course of heart rate, systolic blood pressure, urinary output, and body weight was monitored from weaning to maturity and then compared with those responses from six sex- and age-matched Sprague-Dawley rats grown in a gravity environment (group G). A downward shift in systolic blood pressure and body weight maturation curves was observed in immersion-G rats from the age of 60 days. Cessation of dry water immersion produced a gradual, significant rise in systolic blood pressure but not in body weight to control values. No marked changes in heart rate and urinary output between G and immersion-G rats were noticed throughout the investigation. Our results provide indirect evidence that an interference in the natural history of blood pressure maturation was introduced by immersion, which dissociated the effects of body weight increase during growth from the effects of ageing per se. It is concluded that the physiological increase in systolic blood pressure during growth is partly gravity-dependent.

Bronchopleural fistula following pneumonectomy is a serious and frightening complication in chest surgery with a high mortality rate. The possibility of curing this complication using a conservative treatment is extremely poor. Below we describe a case of a patient affected by left pleural empyema due to a postpneumonectomy bronchopleural fistula. The patient had previously undergone an aortic prosthesis implantation. He was successfully treated using omental pedicle in order to cover the bronchial stump, to fill the pleural space and to protect the aortic prosthesis. He also underwent thoracoplasty to collapse the residual pleural space. The postoperative course was uneventful. During the follow-up, after thirty months, the patient was asymptomatic, and no recurrence of the fistula was present.

Background: The clinical manifestations of resistance to thyroid hormone (RTH) are highly variable, and the impact of RTH on the cardiovascular system has been poorly investigated. Aim: The objective of the study was to evaluate the cardiovascular characteristics of 16 untreated and asymptomatic patients with RTH compared with 16 euthyroid healthy controls to define the cardiovascular involvement in RTH syndrome. Patients and Methods: Sixteen untreated and asymptomatic RTH patients (eight males; aged 33 ± 12 yr, range 21–45 yr) and 16 controls (nine males; aged 33 ± 5 yr, range 24–42 yr) were enrolled. Clinical data, thyroid status, and echocardiographic results were recorded. Results: Heart rate was comparable with that of controls, whereas arterial pressure was higher than controls. Mean interventricular septum diastolic thickness and mean left ventricular (LV) posterior wall diastolic thickness were significantly lower in RTH patients than controls with a consequent significant decrease of the mean LV mass and LV mass indexed by body surface area. Patients also had abnormalities of myocardial relaxation as indicated by a significant increase of peak A and consequent reduction of the early to late ratio. Finally, systemic vascular resistance was significantly higher in RTH patients than controls. Conclusions: Our results suggest the presence of cardiovascular alterations in asymptomatic and untreated RTH patients similar to those reported in hypothyroid patients. Our strict selection likely created a bias in the inclusion of a particular type of RTH patients, who could represent a minority of patients with RTH. However, no correlation was found between the type of mutation and cardiovascular characteristics of RTH patients.