BackgroundWe aimed to assess the current state of PKU screening and management in the region of southeastern Europe.MethodsA survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014.ResultsResponses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from 1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient’s PKU society existed in 7 of 11 countries.ConclusionsThe region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects.

In discussing the 1947 rebellion in the Zafimaniry village in Madagascar, cultural anthropologist Maurice E. Bloch [1] observed that children who have not been involved in the events of that period but who have had these events narrated to them by their elders, appear to ´remember´ these events in a qualitatively similar manner to the elders who have actually experienced them. Specifically, Bloch argues that the hearers of the narratives engage in an imaginative play of “what it was like” thus forming a mental mode which contains both imagery and emotion. In this way, the form, if not necessarily the content, of autobiographical and ´transmitted´memories is alike. In a related field of research in psychology, imagination has been implicated in the formation of false memories. One study has found that imagining performing a simple action can lead to false remembrance of having performed that action [2]. The authors propose that this may be because imagination and the intention to perform an action involve similar cognitive functions. Similarly, another study has demonstrated that imagination is also involved in the formation of more complex false memories involving childhood events [3]. Moreover, both of these studies indicate that while there are some qualitative differences between true and false memories, these differences disappear or diminish as the frequency of imaginings increases. Transmitted memories are not false memories, however it is not unreasonable to propose that the process of their formation is similar. Namely, the aid of imagination during the encoding stage and the repeated recollection of that imaginary scene may lead to transmitted memories being experienced in a qualitatively similar way to autobiographical memories. Thus, the present study will examine the experience of autobiographical and orally transmitted memories for the same events. The focus of events will be from the war in former Yugoslavia in the 1990s. !! References: [1] Bloch, M.E.F. (1996). Autobiographical Memory and the Historical Memory of the More Distant Past. In Bloch, M.E.F., How We Think They Think (pp. 114 - 127). Cumnor Hill, OX: Westview Press. [2] Lampinen, J.M., Odegard, T.N., & Bullington, J.L. (2003). Qualities of Memories for Performed and Imagined Actions. Applied Cognitive Psychology, 17, 881 – 893. [3] Heaps, C.M., & Nash, M. (2001). Comparing Recollective Experience in True and False Autobiographical Memories. Journal of Experimental Psychology, 27, 920 – 930.

BackgroundPatients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient.AimThe aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future.MethodsThis study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992–2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] ± positron emission tomography [PET], or PET − low-dose CT).ResultsMedian age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11–46 months). Median Breslow thickness was 2.10 mm (IQR 1.40–3.40 mm), and 26 % of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35 % of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1–2] vs. 3 [IQR 1–4] for positive deep pelvic nodes; p < 0.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10–0.25) vs. 0.33 (IQR 0.14–0.54); p < 0.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84 % of patients.ConclusionsPatients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

BackgroundNicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction.MethodsThirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later.ResultsIMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p < 0.001). There was significant difference in ST segment elevation before and after primary PCI with administration of Nicorandil (6.9 ± 3.7 mm vs. 1.6 ± 1.6 mm, p < 0.001). Transthoracic Doppler CFR measurement improved after 3 months (2.69 ± 0.38 vs. 2.92 ± 0.54, p = 0.021), as well as WMSI (1.14 ± 0.17 vs. 1.07 ± 0.09, p = 0.004).ConclusionIntracoronary Nicorandil administration after primary PCI significantly decreases IMR, resulting in improved CFR and ventricular function in patients with STEMI undergoing primary PCI.

We present a new method for enhanced sampling for constant-pH simulations in explicit water based on a two-dimensional (2D) replica exchange scheme. The new method is a significant extension of our previously developed constant-pH simulation method, which is based on enveloping distribution sampling (EDS) coupled with a one-dimensional (1D) Hamiltonian exchange method (HREM). EDS constructs a hybrid Hamiltonian from multiple discrete end state Hamiltonians that, in this case, represent different protonation states of the system. The ruggedness and heights of the hybrid Hamiltonian's energy barriers can be tuned by the smoothness parameter. Within the context of the 1D EDS-HREM method, exchanges are performed between replicas with different smoothness parameters, allowing frequent protonation-state transitions and sampling of conformations that are favored by the end-state Hamiltonians. In this work, the 1D method is extended to 2D with an additional dimension, external pH. Within the context of the 2D method (2D EDS-HREM), exchanges are performed on a lattice of Hamiltonians with different pH conditions and smoothness parameters. We demonstrate that both the 1D and 2D methods exactly reproduce the thermodynamic properties of the semigrand canonical (SGC) ensemble of a system at a given pH. We have tested our new 2D method on aspartic acid, glutamic acid, lysine, a four residue peptide (sequence KAAE), and snake cardiotoxin. In all cases, the 2D method converges faster and without loss of precision; the only limitation is a loss of flexibility in how CPU time is employed. The results for snake cardiotoxin demonstrate that the 2D method enhances protonation-state transitions, samples a wider conformational space with the same amount of computational resources, and converges significantly faster overall than the original 1D method.