Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

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Is Going Beyond Rasch Analysis Necessary to Assess the Construct Validity of a Motor Function Scale?

Objective

To examine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.

Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [11C] Harmine Positron Emission Tomography Study

Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [¹¹C] harmine PET to measure MAO-A total distribution volume (MAO-A V_T), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A V_T were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F_2,33=6.8, P=0.003; OFC and VS MAO-A V_T each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F_7,28=2.7, P=0.029). In ASPD, VS MAO-A V_T was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=−0.50 to −0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity.     

Liver sinusoids and sinusoidal cells in patients with agnogenic myeloid metaplasia

The origin of sinusoidal portal hypertension often remains unknown in patients with agnogenic myeloid metaplasia. Four consecutive patients with agnogenic myeloid metaplasia had liver biopsies examined under light and electron microscopy. Two of the four had obvious clinical portal hypertension; of these two, only one had portal vein thrombosis. All four cases showed sinusoidal infiltration by myeloid cells (from very mild to obvious) and an increased perisinusoidal collagen network. Under electron microscopy we observed (a) the collagenization of the Disse space, (b) myeloid cells in the lumen and the Disse space, (c) the transformation of perisinusoidal cells into transitional cells, and (d) fragments of basement membrane-like material. It is possible that all these abnormalities, and not only sinusoidal infiltration, contribute to increase vascular resistance, even when there is no clinical evidence of portal hypertension unrelated to vascular thrombosis.     

Silent ischemia and acute cardiac insufficiency with normal systolic function: diagnostic value of troponin I measurement

The physiopathological mechanisms resulting in increased left ventricular pressures in acute cardiac failure with normal systolic function are not well understood. Although coronary artery disease is commonly associated with acute episodes, the diagnostic value of troponin I measurement and the prevalence of ischaemia as the predisposing factor are not known. Twenty coronary patients (mean age 77 +/- 9 years) in acute cardiac failure with left ventricular ejection fractions of 50% or over and without angina, were studied retrospectively. The diagnostic value of troponin I (cTnI, AxSYM, method) was assessed by comparing with a control group of 16 acute cardiac failure patients without coronary disease. The frequency of hypertension and diabetes in the coronary group was 50 and 45% respectively. At the time of investigation, the pulmonary capillary and systemic arterial pressures were comparable in the coronary patients irrespective of the cTnl value. At threshold levels of 0.5 microgram/l, cTnl had a specificity of 100% and confirmed ischaemia in 60% of the coronary patients. Ischaemia was the commonest predisposing factor for increased cardiac pressures. Over a 268 +/- 101 days follow-up period, half the coronary patients were readmitted for acute cardiac failure and a third of them died. The authors conclude that silent ischaemia is a common predisposing factor for acute cardiac failure in coronary patients with normal systolic function and troponin I measurement is a useful diagnostic help.