Successful pregnancy in a cystic fibrosis patient with a severe impairment of lung function receiving Elexacaftor-Tezacaftor-Ivacaftor [case report].

Before the arrival of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators women with CF and impaired lung function were experiencing a high risk of complications and mortality during and the years after pregnancy. The arrival of the highly efficient CFTR modulator, Elexacaftor-Tezacaftor-Ivacaftor (ETI) resulted in an improvement of lung function, quality of life and fertility. Here we report a case of successful pregnancy and uncomplicated delivery for a CF patient with severely impaired lung function receiving ETI prior to conception

Η επίδραση της ισορροπίας στις τεχνικές δεξιότητες νεαρών ποδοσφαιριστών

Το ποδόσφαιρο είναι ένα πολυσύνθετο άθλημα όπου η καλή απόδοση εξαρτάται από την αλληλεπίδραση διαφορετικών χαρακτηριστικών όπως φυσιολογικών, τακτικών, ψυχολογικών και τεχνικών. Το στοιχείο της τεχνικής ικανότητας αποτελεί ίσως το σημαντικότερο παράγοντα στη διάκριση των ποδοσφαιριστών και στον καθορισμό του επιπέδου τους. Επιπλέον, η διαρκώς αυξανόμενη ταχύτητα του παιχνιδιού σε συνδυασμό με τον περιορισμό του πεδίου δράσης των αθλητών όπως προκύπτει από την ανάπτυξη της σύγχρονης τακτικής επιτάσσει τη δημιουργία αρτιότερων τεχνικά ποδοσφαιριστών. Mια από τις πιο βασικές ικανότητες νευρομυϊκής συναρμογής είναι η ισορροπία (Riccoti et al., 2011). Στο ποδόσφαιρο η εκτέλεση πολλών τεχνικών δεξιοτήτων όπως είναι η μεταβίβαση, το σουτ, ο ελιγμός με μπάλα και το σταμάτημα της μπάλας πραγματοποιούνται ενώ ο ποδοσφαιριστής στηρίζεται στο ένα πόδι. Η ισορροπία επομένως παίζει σημαντικό ρόλο στις συνεχείς αλλαγές κατεύθυνσης που πραγματοποιούνται κατά τη διάρκεια του αγώνα καθώς και στις καταστάσεις εκείνες του παιχνιδιού όπου απαιτείται σωματική επαφή με τον αντίπαλο ή σε συνθήκες ολισθηρού και κακού αγωνιστικού χώρου (Bekris et al, 2012). Το γεγονός ότι οι άνθρωποι ως δίποδα μετακινούνται με το ένα πόδι να στηρίζεται στο έδαφος (περπάτημα), χωρίς κανένα πόδι να στηρίζεται στο έδαφος (τρέξιμο) ή στεκόμαστε με τα δυο πόδια σε αυτό (στάση) δημιουργεί μια σημαντική πρόκληση στο σύστημα ελέγχου της ισορροπίας (Winter, 1995). Σκοπός της παρούσας εργασίας ήταν να εξετάσει την επίδραση της ισορροπίας στις τεχνικές δεξιότητες νεαρών ποδοσφαιριστών. Για την πραγματοποίηση της παρούσας έρευνας έλαβαν μέρος 20 νεαροί ποδοσφαιριστές ηλικίας 12-13 ετών, οι οποίοι αγωνίζονται στην ίδια ποδοσφαιρική ομάδα Α΄ ερασιτεχνικής κατηγορίας της Αθήνας. Στη συγκεκριμένη έρευνα η ισορροπία συσχετίστηκε θετικά μόνο με τη δεξιότητα της πάσας. Αυτό κρίνεται απόλυτα φυσιολογικό λόγω του ότι κατά την διαδικασία της πάσας ο αθλητής στηρίζεται στο ένα πόδι. Προτείνεται να εξεταστεί η επίδραση μιας εξειδικευμένης προπόνησης ισορροπίας στην βελτίωση της και κατ επέκταση στην βελτίωση των τεχνικών ικανοτήτων. Ακόμα προτείνεται η εξερεύνηση της επίδρασης της ισορροπίας και σε άλλες ηλικιακές ομάδες.Football is a complex sport where good performance depends on the interaction of different characteristics such as physiological, tactical, psychological and technical. The element of technical capability is perhaps the most important factor to distinguish the players and determine their level. Moreover, the increasing speed of the game in conjunction with limiting the scope of the athletes as evidenced by the development of modern tactics requires the creation of more informed technical players. One of the most basic skills neuromuscular assembly is balance (Riccoti et al., 2011). In football the performance of many technical skills such as the transfer of the shot, the maneuver to pass the ball stopping place while the player rests on one leg. The balance therefore plays an important role in the continuous direction changes carried out during the race and in those situations where the game requires physical contact with the opponent or in slippery conditions, and bad pitch (Bekris et al, 2012). The fact that people as bipeds moving with one foot resting on the ground (walking), no foot rests on the ground (running) or stand with both feet on it (stop) creates a significant challenge to the balance control system (Winter, 1995). The purpose of this study was to examine the effect of the balance on the technical skills of young players. For the realization of this research took part 20 young players aged 12-13 years, who are fighting on the same football team A recreational class of Athens. In this research, the balance was associated positively with the skill of setting. This is perfectly normal because during the process of the pass the athlete relies on one leg. It is proposed to examine the effect of a specific balance training to improve and therefore to the improvement of technical skills. Even proposed to explore the effect of balance and other age groups

Characterisation and functional analysis of connexins expressed in the retina

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Expression of phosphatase and tensin homologue in imprint smears of endometrial carcinoma

Objective The aims of this study were to determine the expression of phosphatase and tensin homologue (PTEN) in endometrial adenocarcinomas (as a potential prognostic indicator before treatment) in imprint smears and to correlate the results with clinicopathological parameters of primary untreated endometrial cancer patients. Methods Results A total of 126 patients with endometrial carcinoma were evaluated with samples freshly resected after a total abdominal hysterectomy during a 29-month period. The expression of PTEN was assessed by immunocytochemistry. In total, 102 cases were type I and 24 type II endometrial adenocarcinomas. High expression of PTEN was more frequent in type I (42/102) compared to type II (6/24) adenocarcinomas, to less advanced and aggressive clinical stage (stage I: 41/79, stage II: 5/13, stage III: 2/19, stage IV: 1/15) as well as in low grade (grade 1: 26/42, grade 2: 20/57) compared to high-grade (grade 3: 8/27) carcinomas. The nonaffected lymph nodes showed high expression of PTEN (in 43.3%) than the affected lymph nodes (in 5.9%). Also, in 45 out of 74 cases with myometrial invasion <50%, there was positive expression of PTEN in contrast to 12 out of 52 cases with depth of myometrial invasion >50%. Conclusions Immunocytochemical findings from PTEN stain, in addition to cytomorphological features, appeared to be a useful marker in the diagnosis and in the postoperative prognosis of endometrial carcinoma in endometrial cytology with imprint smears and that high PTEN expression is related to morphological features of less aggressiveness tumours

Clinical implementation of preemptive pharmacogenomics in psychiatryResearch in context

Summary: Background: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. Funding: European Union Horizon 2020

First genetic evidence of GABAA receptor dysfunction in epilepsy: A mutation in the γ2-subunit gene

Major advances in the identification of genes implicated in idiopathic epilepsy have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign familial neonatal convulsions and nocturnal frontal lobe epilepsy, three autosomal dominant idiopathic epilepsies, result from mutations affecting voltage-gated sodium and potassium channels, and nicotinic acetylcholine receptors, respectively1-6. Disruption of GABAergic neurotransmission mediated by γ-aminobutyric acid (GABA) has been implicated in epilepsy for many decades7. We now report a K289M mutation in the GABAA receptor γ2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes1,2. The K289M mutation affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. We thus provide the first genetic evidence that a GABAA receptor is directly involved in human idiopathic epilepsy.link_to_subscribed_fulltex