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.

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-cellderived cardiomyocytes does occur in the absence of any neural elements. Even in L. polyphemus, the heart rhythm is myogenic at embryonic stages.

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.

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Background Acute myocardial infarction (MI) is associated with high morbidity and mortality. A robust differentiation between type 1 and type 2 MI (T1/T2MI) has prognostic and therapeutic implications. We investigated whether serial high-sensitivity cardiac troponin I measurements could reliably discriminate T1MI from T2MI in patients presenting with a non-ST elevation myocardial infarction (NSTEMI). Methods We used data from a prospective acute coronary syndrome biomarker registry of patients with suspected MI that presented at or were transferred to one of two study centres. Here, we analysed an unselected group of 265 NSTEMI patients (67.2% males). Blood was drawn on admission and after 3 hours. High-sensitivity troponin I (hs-cTnI) was measured in frozen samples by a technician blinded to patient characteristics. T1MI or T2MI was defined as the gold-standard study diagnosis by two independent cardiologists based on all available data according to the Third Universal Definition of MI. Results A diagnosis of T2MI was made in 55 patients (20.8%) in the NSTEMI cohort. T2MI patients did not differ from T1MI patients regarding age, gender, traditional risk factors, or percentage of those with a history of coronary artery disease. Median baseline hs-cTnI levels were higher in T1MI (436.25; IQR 63.7–1918.8 ng/L) than in T2MI patients (48.4; IQR 11.7–305.9 ng/L; p<0.001). Absolute change in hs-cTnI concentration between 0 and 3 h was greater in T1MI than in T2MI patients with Dhs-cTnI 93.6 ng/L (IQR 13.5–815.3 ng/L) vs. 20.4 ng/L (IQR 2.5–106.5 ng/L) (p<0.001). hs-cTnI yielded an area under the receiver operator characteristics (AUROC) curve for identifying T2MI at baseline of 0.71 (IQR 0.64–0.79) and after 3 h of 0.7 (IQR 0.61–0.78).Dhs-cTnI was associated with an AUROC of 0.68 (IQR 0.6–0.76). Regarding a rule-out approach, Youden-optimized cut-offs for hs-cTnI at baseline as well as for the absolute change in hs-cTnI concentration were calculated (186.5 ng/L; 154.4 ng/L). Use of these two criteria yielded a sensitivity of 89% (78–96%) and a negative predictive value of 95% (89–98%) to exclude T2MI. 49 of 55 T2MI patients would have been ruled out using this algorithm. Conclusion Our data show that hs-cTnI concentrations differ between patients presenting with T1 and T2MI. The concentration of hs-cTnI and its change over time has the potential to rule out T2MI and therefore to identify patients who might benefit from an early invasive management. The differentiation between T1MI and T2MI by using hs-cTnI is nevertheless challenging, and further research on specific algorithms is needed. Acknowledgement/Funding 3German Center for Cardiovascular Research (DZHK), Partnersite Rhein Main, Bad Nauheim, Germany

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Background Cardiac troponins have become the gold standard for appropriate and rapid diagnosis of an acute myocardial infarction (AMI). However, elevated cardiac troponins levels can be observed in the absence of AMI in elderly patients and therefore a loss of specificity is seen in the diagnosis of AMI in elderly patients. Purpose This study aims to define old age in suspected AMI and to evaluate the effect of older age on the diagnostic specificity of a high sensitivity troponin I (hs-cTnI) and high sensitivity troponin T (hs-cTnT) assay in elderly women and men. Methods This study used data from patients with suspected AMI who were enrolled between 08–2011 and 10–2016 to a multicentre biomarker registry and an University Hospital and with available hs-cTnI and hs-cTnT upon admission (n=564 patients). First, we investigated the effect of age on the specificity of both hs-cTnI and hs-cTnT to detect AMI continuously. We then classified over seventy-year-olds as elderly (n=281; 49,8%) and compared the specificity of hs-cTnI and hs-cTnT between elderly and younger patients. Results In the group of older patients, 62.6% (n=176) were diagnosed with AMI compared with 50.9% (n=144) in younger age patients (p&lt;0.01). Elderly patients had higher median levels of hs-cTnI and hs-cTnT than younger patients: 45.4 ng/L vs. 13.1 ng/L hs-cTnI (p&lt;0.001) and 36.8 ng/L vs. 12.8 ng/L hs-cTnT (p&lt;0.001) irrespective of the final diagnosis. Figure1 shows a shift in diagnostic specificity for the whole troponin concentration range in elderly patients compared to younger patients starting at the age of 60 years with clear impact in patients older than 70 years used as threshold for old age in further analyses. Applying the 99th percentile cut-off led to a specificity of 93.5% (95% CI: 88.1–97.0%) in younger patients vs. 88.6% (95% CI: 80.9–94.0%) in elderly patients for hs-cTnI and of 91.4% (95% CI: 85.4–95.5%) vs. 65.7% (95% CI: 55.8–74.7%) for hs-cTnT. To achieve the same specificity in elderly patients as in younger patients, optimized rule-in cut-offs were calculated with 2.6-fold of the 99th percentile for hs-cTnI (68.9 ng/L) and 3.1-fold of the 99th percentile for hs-TnT (43.9 ng/L). Conclusions The specificity of both, hs-cTnI and hs-cTnT is significantly reduced in elderly patients due to higher hs-cTnT and hs-cTnI levels in elderly patients at admission irrespective of the final diagnosis. A relevant loss in diagnostic specificity is observed at 70 years of age starting already at 60 years. Use of assay-specific adjusted cut-offs for hs-cTnI and hs-cTnT for elderly patients regains diagnostic specificity that leads to a more accurate decision-making concerning “rule-in” for older patients with suspected AMI. Funding Acknowledgement Type of funding source: None