Progressive long-term synaptic depression at cortical inputs into the amygdala.

The convergence of conditioned and unconditioned stimuli (CS and US) into the lateral amygdala (LA) serves as a substrate for an adequate fear response in vivo. This well-known Pavlovian paradigm modulates the synaptic plasticity of neurons, as can be proved by the long-term potentiation (LTP) phenomenon in vitro. Although there is an increasing body of evidence for the existence of LTP in the amygdala, only a few studies were able to show a reliable long-term depression (LTD) of excitation in this structure. We have used coronal brain slices and conducted patch-clamp recordings in pyramidal neurons of the lateral amygdala (LA). After obtaining a stable baseline excitatory postsynaptic current (EPSC) response at a holding potential of -70 mV, we employed a paired-pulse paradigm at 1 Hz at the same membrane potential and could observe a reliable LTD. The different durations of stimulation (ranging between 1.5-24 min) were tested first in the same neuron, but the intensity was kept constant. The latter paradigm resulted in a step-wise LTD with a gradually increasing magnitude under these conditions.

Myeloid-related protein 8/14 and high-sensitivity cardiac troponin I to differentiate type 2 myocardial infarction.

Myocardial infarction (MI) not only defines acute MI with obstructed coronary arteries (T1MI) but also myocardial necrosis caused by myocardial oxygen supply/demand mismatch as type 2 MI (T2MI); only T1MI patients benefit from an early invasive management. Myeloid-related protein(MRP)-8/14 is a biomarker described in various inflammatory diseases and in MI patients. Here we evaluate the potential of MRP-8/14 and high-sensitivity troponin I (hs-cTnI) to differentiate T2MI from T1MI. Patients with final diagnosis NSTEMI (n = 254; 33.1% female) enrolled in a prospective biomarker registry between 08/2011 and 10/2016 were analysed. Median baseline MRP-8/14 levels were higher in T2MI (n = 55; 3.37(1.88-6.48)µg/mL) than in T1MI (n = 199; 2.4 [1.4-3.79]µg/mL) (p = .013) patients, in contrast to hs-cTnI (T2MI:52[11.65-321.4]ng/L vs. T1MI:436.5 [61.25-1973.8]ng/L; p < .001). To detect the strength of this association odds ratios(OR) were calculated with MRP-8/14 yielding 2.13(1.16-3.92; p = .015) to predict T2MI and 0.47(0.26-0.87; p = .015) for T1MI. As expected, hs-cTnI yielded an OR of to predict T2MI 0.34(0.17-0.65; p = .001) and 2.98(1.53-5.81; p = .001) for T1MI. Both markers show comparable and independent results if adjust to hs-cTnI/MRP-8/14, TIMI risk score and CRP. T2MI is associated with higher MRP-8/14 and lower hs-cTnI concentrations than T1MI. Our data suggest that MRP-8/14 as a marker of inflammation might provide usable discriminatory information complementing hs-cTnI in a diagnostic procedure evaluating the type of MI directly upon hospital admission.

Limulus and heart rhythm.

Great interest in the comparative physiology of hearts and their functions in Animalia has emerged with classic papers on Limulus polyphemus and mollusks. The recurrent cardiac activity-heart rate-is the most important physiological parameter and when present the kardia (Greek) is vital to the development of entire organs of the organisms in the animal kingdom. Extensive studies devoted to the regulation of cardiac rhythm in invertebrates have revealed that the basics of heart physiology are comparable to mammals. The hearts of invertebrates also beat spontaneously and are supplied with regulatory nerves: either excitatory or inhibitory or both. The distinct nerves and the source of excitation/inhibition at the level of single neurons are described for many invertebrate genera. The vertebrates and a majority of invertebrates have myogenic hearts, whereas the horseshoe crab L. polyphemus and a few other animals have a neurogenic cardiac rhythm. Nevertheless, the myogenic nature of heartbeat is precursor, because the contraction of native and stem-cell-derived cardiomyocytes does occur in the absence of any neural elements. Even in L. polyphemus, the heart rhythm is myogenic at embryonic stages.

Aortic root volume is associated with contained rupture of the aortic annulus in balloon-expandable transcatheter aortic valve replacement.

BACKGROUND: Aortic annulus rupture is a rare, but potentially fatal complication of transcatheter aortic valve replacement (TAVR), especially when it occurs by balloon-expandable devices. In order to improve the predictability of procedures and avoid ruptures we investigated whether or not the aortic root volume measures is a useful indicator of risk, and if it could be useful for the prosthesis size selection. METHODS AND RESULTS: From a retrospective series of 172 TAVR patients, seven experienced contained aortic annulus ruptures. The receiver operating curves were used to illustrate sensitivity and specificity of the different aortic annulus size and aortic root volume measures. The annulus area oversizing of ≥20% resulted in a sensitivity of 100%, specificity of 55.76%, and positive predictive value (PPV) of 8.75%. In patients receiving 26 mm prostheses, the aortic root volume (ARV <13600 mm(3)) provided a better specificity and PPV (79.63 and 18.52%, respectively). A two-step testing procedure considering the area derived average annulus diameter (Darea <23 mm) as a first separating parameter and then the ARV (<13,600 mm(3)) as a further indicator showed the most promising results with the PPV of 31.25%. Regardless of the procedure steps no false negative results were predicted. CONCLUSIONS: Our data show that the ARV provides a better predictive value for correct prosthesis sizing than established annulus measurements, especially in 'borderline' annuli. We suggest a two-step testing procedure for prostheses size selection, considering Darea and ARV to minimize the risk of annulus rupture. Prospective studies and examination of larger datasets are warranted to confirm these findings.

Endogenous cannabinoids trigger the depolarization-induced suppression of excitation in the lateral amygdala.

The amygdala is a key area of the brain where the emotional memories are stored throughout the lifespan. It is well established that synapses in the lateral nucleus of amygdala (LA) can undergo long-term potentiation, a putative cellular correlate of learning and memory. However, a type of short-term synaptic plasticity, known as depolarization-induced suppression of excitation (DSE), has not been studied previously in the amygdala in general and in the LA in particular. In this study we aimed to prove either the absence or the presence of this phenomenon in the LA. Our data demonstrate for the first time that DSE is present in the LA and that it modulates the cortical excitatory synaptic input into this region. The existence of this type of retrograde neurotransmission in glutamatergic pyramidal neurons of the LA suggests that the axonal terminals of cortical inputs do possess functional type 1 cannabinoid receptors, and provides a novel insight regarding inputs into the LA. Further experiments indeed revealed endocannabinoids as the messenger for this retrograde signaling in the LA. In conclusion, the DSE may play a functional role in synaptic plasticity and related emotional memory processing in the LA.