Συγκριτική Διερεύνηση Υλοτομιών με Φωτοερμηνεία Ορθοφωτοχαρτών και Αντικειμενοστρεφή Ανάλυση Landsat Απεικονίσεων. Μελέτη Περίπτωσης Λίμνη Πλαστήρα

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Περιβάλλον και Ανάπτυξη

Σύνδρομο Koolen de Vries

H αναγνώριση των συνδρόμων μικροελλείμματος και μικροδιπλασιασμού της χρωμοσωμικής περιοχής 17q21.31 έχει γίνει δυνατή μόνο μετά την εφαρμογή της νέας τεχνολογίας του μοριακού καρυοτύπου ή μικροσυστοιχίας του συγκριτικού γενωμικού υβριδισμού (array-CGH). Στη βιβλιογραφία έχουν αναφερθεί τουλάχιστον 80 περιστατικά με το σύνδρομο Koolen de Vries (KdVS). Με τη μοριακή ανάλυση αναδείχθηκε ότι στην περιοχή 17q21.31 εντοπίζονται τουλάχιστον 6 κρίσιμα για το φαινότυπο γονίδια, με σημαντικότερα τα STH και MAPT. Η συχνότητα του συνδρόμου μικροελλείματος 17q21.31 εκτιμάται στις 1/16000 γεννήσεις ενώ, μέχρι στιγμής έχουν περιγραφεί μόνο επτά ασθενείς με σύνδρομο μικροδιπλασιασμού 17q21.31. Ο φαινότυπος που σχετίζεται με μικροδιπλασιασμούς 17q21.31 φαίνεται να είναι ηπιότερος σε σχέση με τα σύνδρομα μικροελλείμματος 17q21.31. Πρόσφατα περιγράφηκε επίσης ό,τι η απλοανεπάρκεια του KANSL1 και μόνο αρκεί να οδηγήσει στον πλήρη φαινότυπο του συνδρόμου, εξαιτίας ενός πολυμορφισμού ή ενός γονιδιακού ελλείματος. Στην παρούσα μελέτη καταγράφηκαν από το τμήμα Kλινικής Γενετικής του Πανεπιστημίου Αθηνών, 19 ασθενείς με το σύνδρομο Koolen de Vries, 6 απο αυτούς ήταν ενήλικες. Η πλειοψηφία των ασθενών παραπέμφθηκαν από τον παιδίατρο ή τον αναπτυξιολόγο για γενετικό έλεγχο λόγω ψυχοκινητικών διαταραχών . Σε 17 ασθενείς διαγνώσθηκε έλλειμα στην περιοχή 17q21.31, σε έναν ασθενή μικροδιπλασιασμό στην περιοχή 17q21.31 και στον τελευταίο μια παθολογική de novo σημειακή μετάλλαξη (c.1448G>A) του KANSL1 γονιδίου. Oι ψυχοκινητικές διαταραχές, η νοητική στέρηση, τα δυσμορφικά χαρακτηριστικά προσώπου και η καθυστέρηση λόγου φαίνεται να είναι οι πιο συχνές εκδηλώσεις του συνδρόμου. Ενδιαφέρον εύρημα στην μελέτη μας είναι ο,τι η ανάλυση μέσω του μοριακού καρυρότυπου ανέδειξε ο,τι σε 4 ασθενείς με ψυχοκινητική καθυστέρηση εκτός από το ελλείμμα στην περιοχή 17q21.31 υπήρχε και έλλειμμα ή μικροδιπλασιασμός στην περιοχή του μακριού σκέλους του χρωμοσώματος 15 .The deletion or microduplication of the 17q21.31 region was recognised only with the development of the array-CGH technique. The 17q21.31 region, typically encompassing at least 6 critical genes related to the phenotype (ie STH and MAPT). Recently, it has been shown that haploinsufficiency of KANSL1 by itself, due to single nucleotide variants or gene deletion, is sufficient to cause the full-blown phenotype of the disorder of Koolen-de Vries syndrome. The frequency of this syndrome is estimated at 1/16000 whereas only seven cases have been described so far with microduplication of the 17q21.31 region. Patients with microduplications have a less severe phenotype compare to the syndrome with deletions. In total at least 80 cases of Koolen de Vries syndrome have been described in the literature. In the present study, 19 patients with Koolen de Vries syndrome have been registrated and diagnosed in the laboratory of Medical Genetics of the National and Kapodistrian University of Athens, 6 of them were adults. The majority of the patients was addressed for genetical analysis due to psychomotor retardation. Seventeen patients presented deletion of the 17q21.31 region, 1 patient presented microduplication and the last one, de novo pathological mutation (c.1448G>A) of the KANSL1 gene. Interestingly, we also found 4 patients with the phenotype of KdVS due to the deletion in the 17q21.31 region indluding KANSL1 who also presented (through array-CGH technique) deletion or microduplication of the 15q region

The value of PRL in predicting prolactinοma in hyperprolactinemic PCOS

Background To identify a serum prolactin (PRL) cut‐off value indicative of a PRL‐producing adenoma in women with Polycystic Ovarian Syndrome (PCOS) and hyperprolactinemia and characterize such patients. Materials and methods In the present retrospective case‐control study the medical records of 528 PCOS women were reviewed. Pituitary magnetic resonance imaging (MRI) was performed in PCOS patients with PRL levels ≥94.0 ng/mL and/or symptoms suspicious of a pituitary adenoma (PA). Prolactinoma diagnosis was made in the presence of an MRI‐identifiable PA with biochemical and radiological response to dopamine agonists. Receiver operating characteristic (ROC) curve analysis was performed to determine a serum PRL threshold that could identify hyperprolactinemic PCOS subjects with prolactinomas. Clinical, metabolic and endocrine parameters were also analysed. Results Among 528 patients with PCOS, 60 (11.4%) had elevated PRL levels. Of 44 (73.3%) patients who had pituitary imaging, 19 had PAs, 18 normal MRI and 7 other abnormalities. Patients harboring prolactinomas had significantly higher PRL levels compared to patients without adenomas (median PRL 95.4 vs. 49.2 ng/mL, p<0.0001). A PRL threshold of 85.2 ng/mL could distinguish patients with prolactinomas with 77% sensitivity and 100% specificity [Area Under the curve (AUC) (95%) 0.91(0.8‐1.018), p=0.0001]. PCOS women with prolactinomas were younger and had lower LH levels compared to women without prolactinomas. Conclusions In women with PCOS, PRL levels exceeding 85.2 ng/mL are highly suggestive of a prolactinoma warranting pituitary imaging. Pituitary MRI could also be considered in young PCOS patients with milder PRL elevation and low LH levels

Endothelin‐receptor antagonists for diabetic nephropathy: A meta‐analysis

AimEndothelin‐receptor antagonists may be a novel therapeutic strategy for diabetic nephropathy, but their use remains controversial. This meta‐analysis seeks to evaluate the effectiveness and safety of endothelin‐receptor antagonists for patients with diabetic nephropathy.MethodsLiterature reviews of the PubMed, EMBASE and CENTRAL databases were conducted to identify randomized controlled trials (RCTs) comparing endothelin‐receptor antagonist treatment with placebo in patients with diabetic nephropathy. Quality assessment was performed by using the Cochrane Handbook's tools for assessing risk of bias; meta‐analysis was conducted by RevMan 5.3.ResutlsFive RCTs (n = 2034 patients) were included for analysis. Compared with placebo, endothelin‐receptor antagonists showed significant benefits for lowering albuminuria (five trials, n = 2034 patients; SMD 0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant difference in the risk of death (two trials, n = 1674 patients; RR 1.49 95% CI 0.81 to 2.76). In addition, risk of cardiovascular events and other serious adverse events were significantly higher in the endothelin‐receptor antagonists group than the placebo group (four trials, n = 1956 patients; RR 1.45 95% CI 1.07 to 1.97; five trials, n = 2034 patients; RR 1.32 95% CI 1.10 to 1.58).ConclusionEndothelin‐receptor antagonists can reduce albuminuria in patients with diabetic nephropathy, although use resulted in more serious adverse events compared with placebo. There is a potential need for further RCTs, which has larger sample size and longer duration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111994/1/nep12442.pd

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

Epidemiological and in vitro data have not provided conclusive evidence concerning the involvement of thyroid hormones (THs) on mammary carcinogenesis. We used an in vivo model to assess the relationship between THs, adipose tissue and breast cancer development. Female Sprague‑Dawley rats were treated with a dose of 7,12-dimethylbenz(a)anthracene (15 mg/rat) at 55 days of age and were then divided into four experimental groups: hypothyroid rats (HypoT, 0.01% 6-N-propyl-2-thiouracil in drinking water), untreated control (EUT); hyperthyroid rats (HyperT, 0.25 mg/kg/day T4 s.c.) and vehicle-treated control rats. The latency of tumor appearance and the incidence and progression of tumors were determined. At sacrifice, blood samples were collected for hormone determinations and samples of tumor and mammary glands were obtained for immunohistological studies. HypoT rats had retarded growth and an increase in mammary fat. The latency was longer (p<0.0001), the incidence rate was lower (p<0.05) and tumor growth was slower in HypoT rats compared to EUT and HyperT rats. Mitotic index and PCNA immunostaining were similar in all groups. HypoT rats showed increased apoptosis (p<0.05) as evaluated by the apoptotic index and TUNEL staining. No differences in serum prolactin and progesterone were observed. However, circulating estradiol (E2) was significantly lower in HypoT and HyperT rats. Serum leptin levels were reduced in HypoT rats even though the abdominal fat mass was similar in all groups. To note, the leptin level was higher in HypoT rats that developed mammary tumors than the level in non-tumoral HypoT rats. In conclusion, hypothyroidism altered animal growth, breast morphology, body composition, leptin secretion and serum E2 enhancing apoptosis and, consequently, retarding mammary carcinogenesis in rats.Fil: López Fontana, Constanza Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Sasso, Corina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Maselli, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Santiano, Flavia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Semino, Silvana Noemi. Universidad Nacional de Cuyo. Hospital Universitario. Laboratorio de Anatomía Patológica; Argentina;Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Caron, Ruben Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina

Effectiveness of non-pharmacological interventions to treat orthostatic hypotension in elderly people and people with a neurological condition

Acceptance date approximate, given by author

ENSAT registry-based randomized clinical trials for adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease