High-frequency QRS analysis compared to conventional ST-segment analysis in patients with chest pain and normal ECG referred for exercise tolerance test

Background: The novel analysis of high-frequency QRS components (HFQRS-analysis) has been proposed in patients with chest pain (CP) and normal electrocardiography (ECG) referred for exercise tolerance test (ex-ECG). The aim of the study was to compare the diagnostic value of ex-ECG with ex-HFQRS-analysis. Methods: Patients with CP and normal ECG, troponin, and echocardiography were consid­ered. All patients underwent ex-ECG for conventional ST-segment-analysis and ex-HFQRS-analysis. A decrease ≥ 50% of the HFQRS signal intensity recorded in at least 2 contiguous leads was considered an index of ischemia, as ST-segment depression ≥ 2 mm or ≥ 1 mm and CP on ex-ECG. Exclusion criteria were: QRS duration ≥ 120 ms and inability to exercise. End-point: The composite of coronary stenosis ≥ 70% or acute coronary syndrome, revascu­larization, cardiovascular death at 3-month follow-up. Results: Three-hundred thirty-seven patients were enrolled (age 60 ± 15 years). The percent­age of age-adjusted maximal predicted heart rate was 89 ± 10 beat per minute and the maximal systolic blood pressure was 169 ± 23 mm Hg. Nineteen patients achieved the end-point. In multivariate analysis, both ex-ECG and ex-HFQRS were predictors of the end-point. The ex-HFQRS-analysis showed higher sensitivity (63% vs. 26%; p < 0.05), lower specificity (68% vs. 95%; p < 0.001), and comparable negative predictive value (97% vs. 96%; p = 0.502) when compared to ex-ECG-analysis. Receiver operator characteristics analysis showed the incremental diagnostic value of HFQRS (area: 0.655, 95% CI 0.60–0.71) over conventional ex-ECG (0.608, CI 0.55–0.66) and CP score (0.530, CI 0.48–0.59), however without statistical significance in pairwise comparison by C-statistic. Conclusions: In patients with CP submitted to ex-ECG, the novel ex-HFQRS-analysis shows a valuable incremental diagnostic value over ST-segment-analysis

Paediatric-type diffuse high-grade gliomas in the 5th CNS WHO Classification

As a relevant element of novelty, the fifth CNS WHO Classification highlights the distinctive pathobiology underlying gliomas arising primarily in children by recognizing for the first time the families of paediatric-type diffuse gliomas, both high-grade and low-grade. This review will focus on the family of paediatric-type diffuse high-grade gliomas, which includes four tumour types: 1) Diffuse midline glioma H3 K27-altered; 2) Diffuse hemispheric glioma H3 G34-mutant; 3) Diffuse paediatric-type high-grade glioma H3-wildtype and IDH-wildtype; and 4) Infant-type hemispheric glioma. The essential and desirable diagnostic criteria as well as the entities entering in the differential will be discussed for each tumour type. A special focus will be given on the issues encountered in the daily practice, especially regarding the diagnosis of the diffuse paediatric-type high-grade glioma H3-wildtype and IDH-wildtype. The advantages and the limits of the multiple molecular tests which may be utilised to define the entities of this tumour family will be evaluated in each diagnostic context

Il ruolo dell’Apratassina (APTX) nel riparo delle rotture del DNA a singolo filamento

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. Il ruolo dell’apratassina (APTX) nel riparo delle rotture del dna a singolo filamento

Recentemente è stato dimostrato che l’apratassina (APTX), la proteina mutata nell’Atassia con Aprassia Oculomotoria di tipo 1 (AOA1), gioca un ruolo nella riparazione delle rotture a singolo filamento del DNA (SSBs). Per confermare il coinvolgimento dell’apratassina nel “SSB Repair”, i linfociti primari di un paziente AOA1, omozigote per la mutazione troncante G837A, sono stati trattati con camptotecina (CPT), un inibitore della Topoisomerasi I (topo I) e potente induttore di rotture a singolo filamento. Il danno indotto è stato valutato attraverso lo studio delle aberrazioni cromosomiche. L’analisi citogenetica ha messo in evidenza un aumento significativo di aberrazioni cromosomiche indotte dalla CPT nei linfociti del paziente AOA1. Nello stesso paziente, nei linfociti in G0, è stato riscontrato un aumento significativo di cromosomi dicentrici indotti dai raggi X, rispetto alla risposta osservata in un controllo normale. Mentre la frequenza di cellule con aberrazioni cromosomiche è la stessa nell’individuo di controllo e nel paziente, indicando una risposta normale delle cellule AOA1 alle radiazioni ionizzanti, l’aumento della frequenza di dicentrici nei linfociti del paziente AOA1 sembra essere influenzata da un difetto di riparazione dei SSBs. Tale ipotesi è stata ulteriormente confermata trattando le cellule con Ara-C, un inibitore dei sistemi di escissione e riparo del DNA. Inoltre, cellule derivate dalla linea linfoblastoide di un altro paziente AOA1, omozigote per una nuova mutazione C739T, sono state trattate con H2O2, KBrO3, MMS, EMS, induttori di SSBs sia diretti che indiretti. Il trattamento con queste sostanze non ha evidenziato nessun aumento di aberrazioni cromosomiche nella linea del paziente rispetto a quella di un individuo eterozigote e di un controllo intrafamiliare. Per tale paziente era stata precedentemente dimostrata ipersensibilità alla CPT

Study of a Family Presenting Novel Mutation of the TCOF1 Gene Associated with Treacher Collins Syndrome

Treacher Collins syndrome (TCS), due to a mutation in the treacle gene (5q31-32), is the most common type of Mandibulofacial Dysostosis (MDF). The most important features of the considered diseases are hypoplasia, micrognathia, microtia, conductive hearing loss, and cleft palate. In this paper molecular and clinical analysis in a family with several members affected by MFD are reported. Clinical signs as well as inheriting pattern have been considered to reach a correct diagnosis. As genealogic tree showed Autosomic Dominant pattern (AD), Autosomic recessive diseases were not considered in different diagnosis. Furthermore, pathognomonic signs drew us to focus the attention on the possibility that Treacher Collins Syndrome occurred.The molecular research of gene TCOF1 confirmed the presence of a mutation that have never been described in literature before now (c.599delG.). MFD occurs in clinical and genetic different typologies of diseases, and in most cases a certain diagnosis can be reached by means of molecular genetics analysis

Hormonal and psychological influences on performance anxiety in adolescent female volleyball players: a multi-approach study

Background The neuroendocrine system has important implications for affiliation behavior among humans and can be used to assess the correlation between social relationships, stress, and health. This can be influenced by social closeness; this aspect is the closeness towards another individual or a group of individuals such as a sports team. Sports performance anxiety is considered an unpleasant emotional reaction composed of physiological, cognitive, affective, and behavioral components. This motivates us to learn about the process that can influence the outcome of competition. Hormones and genetics would seem to influence outcome and performance. In this regard, many studies have focused on the exercise response as a function of ovarian hormones and it has been observed that progesterone is a hormone that plays a key role in reducing anxiety, and thus stress, in humans and other animals. On the other hand, high cortisol concentrations are known to contribute to increased anxiety levels. However, the salivary alpha-amylase (sAA) enzyme has been suggested as marker of acute stress than cortisol. Genetics also seem to influence anxiety and stress management as in the case of brain-derived neurotrophic factor (BDNF) and striatal dopamine transporter (DAT). Therefore, the study aims to investigate social closeness, as a measure of sports team cohesion that can influence athletes’ performance results, and its ability to influence the secretion of hormones, such as progesterone and cortisol, that affect the management of sports anxiety while also taking into account genetic background during a volleyball match. Methods Twenty-six female volleyball players who volunteered participated in this study (mean ± SD: age, 12.07 ± 0.7 years), and played in the final of the provincial volleyball championship in Palermo. All girls were during the ovarian cycle, in detail between the follicular and early ovulatory phases. Results The results showed a significant decrease in salivary cortisol only in the winning group (p < 0.039). In fact, whilst in the latter the pre-match level was 7.7 ng/ml and then decreased to 4.5 ng/ml after the match, in the losers group change was not statistically significant (7.8 ng/ml vs 6.6 ng/ml pre- and post-match). As to the sAA concentration, the winning team showed a statistically significant variation between pre- and post-match than the losers (166.01 ± 250 U/ml vs 291.59 ± 241 U/ml) (p = 0.01). Conclusion Analyzing the results of the SAS-2 psychological test it is highlighted that, on average, the loser group was more anxious than the winning group, and this contributed to the final result. In conclusion, there is strong evidence supporting the state of the art that many factors can affect performance anxiety and thus the performance itself

A simplified way for the urgent treatment of somatic pain in patients admitted to the emergency room: the SUPER algorithm

Somatic pain is one of the most frequent symptoms reported by patients presenting to the emergency department (ED), but, in spite of this, it is very often underestimated and under-treated. Moreover, pain-killers prescriptions are usually related to the medical examination, leading to a delay in its administration, thus worsening the patient's quality of life. With our study, we want to define and validate a systematic and homogeneous approach to analgesic drugs administration, testing a new therapeutic algorithm in terms of earliness, safety, and efficacy. 442 consecutive patients who accessed our ED for any kind of somatic pain were enrolled, and then randomly divided into two groups: group A follow the normal process of access to pain-control drugs, and group B follow our SUPER algorithm for early administration of drugs to relieve pain directly from triage. We excluded from the study, patients with abdominal pain referred to the surgeon, patients with headache, recent history of trauma, history of drug allergies, and life-threatening conditions or lack of cooperation. Drugs used in the study were those available in our ED, such as paracetamol, paracetamol/codeine, ketorolac-tromethamine, and tramadol-hydrochloride. Pain level, risk factors, indication, and contraindication of each drug were taken into account in our SUPER algorithm for a rapid and safe administration of it. The Verbal Numeric Scale (VNS) and the Visual Analog Scale (VAS) were used to verify the patient's health and perception of it. Only 59 patient from group A (27.1 %) received analgesic therapy (at the time of the medical examination) compared to 181 patients (100 %) of group B (p < 0.001). Group B patients, received analgesic therapy 76 min before group A subjects (p < 0.01), resulting in a significant lower VNS (7.31 ± 1.68 vs 4.75 ± 2.3; p < 0.001), and a superior VAS after discharge (54.43 ± 22.16 vs 61.30 ± 19.13; p < 0.001) compared to group A subjects. No significant differences concerning side effects were observed between group A and group B patients. Early administration of a pain-control therapy directly from triage is safe and effective, and significantly improves patients perceptions of their own health

Different Mechanisms Cause Hypomethylation of Both H19 and KCNQ1OT1 Imprinted Differentially Methylated Regions in Two Cases of Silver-Russell Syndrome Spectrum

Silver-Russell syndrome is an imprinting disorder characterised by pre- and post-natal growth retardation and several heterogeneous molecular defects affecting different human genomic loci. In the majority of cases, the molecular defect is the loss of methylation (LOM) of the H19/IGF2 differentially methylated region (DMR, also known as IC1) at the telomeric domain of the 11p15.5 imprinted genes cluster, which causes the altered expression of the growth controlling genes, IGF2 and H19. Very rarely, the LOM also affects the KCNQ1OT1 DMR (also known as IC2) at the centromeric domain, resulting in an SRS phenotype by an unknown mechanism. In this study, we report on two cases with SRS features and a LOM of either IC1 and IC2. In one case, this rare and complex epimutation was secondary to a de novo mosaic in cis maternal duplication, involving the entire telomeric 11p15.5 domain and part of the centromeric domain but lacking CDKN1C. In the second case, neither the no 11p15.5 copy number variant nor the maternal-effect subcortical maternal complex (SCMC) variant were found to be associated with the epimutation, suggesting that it arose as a primary event. Our findings further add to the complexity of the molecular genetics of SRS and indicate how the LOM in both 11p15.5 DMRs may result from different molecular mechanisms

Expanding the spectrum of EWSR1-PATZ1 rearranged CNS tumors: An infantile case with leptomeningeal dissemination

We report on a case of EWSR1-PATZ1 rearranged brain tumor occurring in a 17 month-old child, originally interpreted as an infantile glioblastoma. Our case shows important analogies with the 2 previously reported cases, including the intraventricular location, the histologic appearance (pushing borders, oligodendrocyte-like morphology, rich vascular network) and the glioneural immunophenotype, supporting the role of these features as relevant clues to the diagnosis. On the other hand, our case displays unique characteristics, i.e. the onset in an infant, the presence of a focal high-grade component and the leptomeningeal dissemination, pointing to the importance of considering this entity in the differential diagnosis of an infantile glial/glioneural tumor