Wittgenstein's Non-non-cognitivism

In this paper, we present one of the main starting points of naturalism in ethics: Geach’s challenge against non-cognitivism. We try to find an answer to Geach’s challenge in the notion of family resemblance applied to ethics. In doing so we recover a not much-discussed influence of Moore on Wittgenstein’s conception of family resemblance, which leads us to define Wittgenstein as non-non-cognitivist in ethics

PVF velocity pattern in patients with heart failure: Transesophageal echocardiographic assessment

In order to assess the role of the pulmonary venous flow (PVF) velocity pattern in the evaluation of patients with congestive heart failure (CHF), we studied 41 CHF patients by means of transthoracic echocardiography (TTE) and multiplane transesophageal echocardiography (TEE). The etiology of CHF was idiopathic or ischemic dilated cardiomyopathy in 19 patients and hypertensive heart disease in 22. Sixteen subjects without cardiovascular disease were selected as normal controls. PVF peak systolic and peak early diastolic (D) velocities were recorded by TEE and TTE and the systolic fraction (SF) was measured (i.e., the systolic velocity-rime integral - VTI - expressed as a fraction of the sum of systolic and early diastolic VTI). TEE tracings were obtained in all patients and had more laminar-appearing spectral signals, thus were used for analysis. By TTE the mitral flow velocity patterns were also evaluated: peak early diastolic velocity (E), peak velocity at atrial contraction, E velocity normalized for VTI (E/VTI), deceleration time (DT), and left ventricular isovolumic relaxation time (LVIRT). The left ventricular ejection fraction (LVEF) was calculated by two-dimensional echocardiographic images using the modified Simpson method. The SF was lower in CHF patients as compared with normal controls (p 50 cm/s; type B: SF similar to 50%, D > 50 cm/s) were recognized in patients with a low LVEF (type A) and a nearly normal or normal LVEF (type B). Patients with LVEF 40% (33.26 +/- 10.84 vs. 51.00 +/- 4.00%, p 40%. Thus in CHF patients TEE PVF velocity patterns help in distinguishing patients with systolic dysfunction (low LVEF and SF) from patients with predominant diastolic impairment (normal or nearly normal LVEF, high D velocities)

Repair or prosthesis insertion in ischemic mitral regurgitation: Two faces of the same medal

AbstractObjectiveThe proper treatment of chronic ischemic mitral regurgitation (CIMR) is still under evaluation. The different role of mitral valve repair (MVr) or mitral valve prosthesis insertion (MVPI) is still not defined.MethodsFrom May 2009 to December 2011 167 patients with ejection fraction (EF) ≤ 40% had MV surgery for CIMR, MVr in 135 (80.8%) and MVPI in 32 (19.2%). Indication to MVPI was a MV coaptation depth > 10 mm. EF was lower (26 ± 7 vs 32 ± 6, p = 0.0000) in MVPI, whereas MR grade (3.6 ± 0.8 vs 2.7 ± 0.9, p = 0.0000), left ventricle dimensions (end diastolic, LVEDD, 62 ± 7 vs 57 ± 6 mm, p = 0.0001; end systolic, LVESD, 49 ± 8 vs 44 ± 8 mm, p = 0.0018), systolic pulmonary artery pressure (51 ± 22 vs 41 ± 16 mm Hg, p = 0.0037) and NYHA Class (3.6 ± 0.5 vs 2.8 ± 0.6, p = 0.0000) were higher.ResultsIn-hospital mortality was similar (3.1 vs 3.7%) as well as 3-year survival (86 ± 6 vs 88 ± 4) and survival in NYHA Class I/II (80 ± 5 vs 83 ± 4). One hundred thirty nine patients had an echocardiographic evaluation after a minimum of 4 months (13 ± 8). EF rose significantly in both groups (from 26 ± 7% to 30 ± 4%, p = 0.0122, and from 32 ± 6% to 35 ± 8%, p = 0.0018). LVESD reduced significantly in both groups (from 49 ± 8 to 43 ± 9 mm, p = 0.0109, and from 44 ± 8 to 41 ± 7 mm, p = 0.0033). MR grade was significantly lower in patients who had MVPI (0.1 ± 0.2 vs 0.3 ± 0.3, p = 0.0011).ConclusionsWith appropriate indications, MVPI is a safe procedure which provides similar results to MVr with lower MR return, even if addressed to patients with worse preoperative parameters

Transesophageal dipyridamole echocardiography for diagnosis of coronary artery disease.

The value of transthoracic dipyridamole echocardiography has been extensively documented. However, in some patients, because of a poor acoustic window, the rest transthoracic examination is not always feasible and the transesophageal approach is more convenient. Therefore, transesophageal echocardiography with high dose dipyridamole (up to 0.84 mg/kg body weight over 10 min) was performed in 32 patients in whom the transthoracic dipyridamole test either was not feasible (n = 29) or yielded ambiguous results (n = 3). The transesophageal echocardiographic test results were considered abnormal when new dipyridamole-induced regional wall motion abnormalities were observed. All 32 patients underwent coronary angiography; significant coronary artery disease was defined as greater than or equal to 70% lumen diameter narrowing in at least one major vessel. All patients also performed a bicycle exercise test 1 day before transesophageal dipyridamole echocardiography. Transesophageal stress studies were completed in all patients, with a maximal imaging time (in tests with a negative result) of 20 min. No side effects or intolerance to drug or transducer was observed. The left ventricle was always visualized in the four-chamber and transgastric short-axis views. High quality two-dimensional echocardiographic images were obtained in all patients both at rest and at peak dipyridamole infusion and were digitally analyzed in a quad-screen format. Coronary angiography showed coronary artery obstruction in 24 patients: 6 had single-, 9 double- and 9 triple-vessel disease. The transesophageal dipyridamole test showed a specificity of 100% and an overall sensitivity of 92%. The sensitivity of this test for single-, double- and triple-vessel disease was 67%, 100% and 100%, respectivel

Paraoxonase 1 L55M, Q192R and paraoxonase 2 S311C alleles in atherothrombosis

Increased oxidative stress is known to play a role in the pathogenesis of atherosclerosis, and polymorphisms in genes encoding for enzymes involved in modulation of oxidant stress, such as paraoxonases (PONs), provide a potentially powerful approach to study the risk of disease susceptibility. Aim of our study is to investigate the possible association among PONs polymorphisms, clinical and metabolic factors, and atherothrombotic events in an Italian population. We evaluated in 105 subjects, with or without atherosclerotic risk factors, the presence of PON1 L55M, PON1 Q192R, and PON2 S311C genetic variants, as well as lipid profile, the concentration of aminothiols (blood reduced glutathione, plasma total glutathione, homocysteine, cysteine, cysteinyl glycine), and malondialdehyde as markers of lipid peroxidation

Different ataxin-3 amyloid aggregates induce intracellular Ca2+ deregulation by different mechanisms in cerebellar granule cells

AbstractThis work aims at elucidating the relation between morphological and physicochemical properties of different ataxin-3 (ATX3) aggregates and their cytotoxicity. We investigated a non-pathological ATX3 form (ATX3Q24), a pathological expanded form (ATX3Q55), and an ATX3 variant truncated at residue 291 lacking the polyQ expansion (ATX3/291Δ). Solubility, morphology and hydrophobic exposure of oligomeric aggregates were characterized. Then we monitored the changes in the intracellular Ca2+ levels and the abnormal Ca2+ signaling resulting from aggregate interaction with cultured rat cerebellar granule cells. ATX3Q55, ATX3/291Δ and, to a lesser extent, ATX3Q24 oligomers displayed similar morphological and physicochemical features and induced qualitatively comparable time-dependent intracellular Ca2+ responses. However, only the pre-fibrillar aggregates of expanded ATX3 (the only variant which forms bundles of mature fibrils) triggered a characteristic Ca2+ response at a later stage that correlated with a larger hydrophobic exposure relative to the two other variants. Cell interaction with early oligomers involved glutamatergic receptors, voltage-gated channels and monosialotetrahexosylganglioside (GM1)-rich membrane domains, whereas cell interaction with more aged ATX3Q55 pre-fibrillar aggregates resulted in membrane disassembly by a mechanism involving only GM1-rich areas. Exposure to ATX3Q55 and ATX3/291Δ aggregates resulted in cell apoptosis, while ATX3Q24 was substantially innocuous. Our findings provide insight into the mechanisms of ATX3 aggregation, aggregate cytotoxicity and calcium level modifications in exposed cerebellar cells

Automatic Morphological Analysis of Medial Temporal Lobe

n/

IPO-V2: A prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction

AbstractObjectives. This study was conducted to assess the efficacy of sulodexide, a glycosaminoglycan compound with antithrombotic properties, in preventing death and thromboembotic events after acute myocardial infarction.Background. Antithrombotic therapy has been found to play an important role in the prevention of cardiovascular events and death after acute myocardial infarction. Glycosaminoglycan-containing compounds, including sulodexide, show profibrinolytic and antithrombotic properties that render them suitable for use in patients after infarction.Methods. A total of 3,986 patients who had recovered from acute myocardial infarction were randomized to receive either the standard therapy routinely administered at each study center, excluding antiplatelet and anticoagulant drugs (control group, 1,970 patients), or the standard therapy plus sulodexide (treated group, 2,016 patients). Between 7 and 10 days after the episode of acute myocardial infarction, sulodexide was administered as a single daily 600-lipoprotein-lipase-releasing unit (LRU) intramuscular injection for the 1st month, followed by oral capsules of 500 LRU twice daily. Patients were evaluated for ≥12 months.Results. At the end of the study, 140 (7.1%) were recorded in the control group and 97 (4.8%) in the sulodexide group (32% risk reduction, p = 0.0022, chi-square test). A total of 90 patients (4.6%) in the control group had a further infarction, compared with 66 (33%) in the sulodexide group (28% risk reduction, p = 0.035). Furthermore, a reduction in left ventricular thrombus formation (evaluated by echocardiography) was observed in the sulodeside group (n = 12; 0.6%), compared with values in the control group (n = 25; 1.3%) (53% risk reduction, p = 0.027). Sulodexide was well tolerated and devoid of significant adverse events. All significant results were confirmed by “actual treatment” analyses.Conclusions. The study provides evidence that long-term therapy with sulodexide started early after an episode of acute myocardial infarction is associated with reductions in total mortality, rate of reinfarction and mural thrombus formation

Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study

Serious bacterial infections (SBI) in children are associated with considerable morbidity and mortality, and their early identification remains challenging. The role of laboratory tests in this setting is still debated, and new biomarkers are needed. This prospective, observational, single-center study aims to evaluate the diagnostic role of blood biomarkers in detecting SBI in children presenting with signs of systemic inflammatory response syndrome (SIRS). A panel of biomarkers was performed, including C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), absolute neutrophil count (ANC), interleukin (IL)-6, IL-8, IL-10, human terminal complement complex (C5b-9), Plasmalemma-Vesicle-associated protein 1 (PV-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Phospholipase A2 (PLA2). Among 103 patients (median age 2.9 years, 60% males), 39 had a diagnosis of SBI (38%). Significant predictors of SBI were CRP (p = 0.001) and ICAM-1 (p = 0.043). WBC (p = 0.035), ANC (p = 0.012) and ANC/WBC ratio (p = 0.015) were also significantly associated with SBI in children without pre-existing neutropenia. ROC curves, however, revealed suboptimal performance for all variables. Nevertheless, a model that combined CRP and ANC/WBC ratio had more in-depth diagnostic accuracy than either of the two variables. Overall, this study confirms the limited usefulness of blood biomarkers for the early diagnosis of SBI. WBC, ANC, ANC/WBC ratio, CRP, and ICAM-1 showed the best, albeit moderate, diagnostic accuracy