Μελέτη πολυμορφισμών του γονιδίου ANRIL σε γυναίκες που ακολουθούν πρωτόκολλα εξωσωματικής γονιμοποίησης

Οι πολυμορφισμοί είναι ευρέως γνωστοί ως επιγενετικές μεταλλάξεις του γονιδιώματος και ευθύνονται για τη μοναδικότητα και την ποικιλομορφία των ειδών. Σε αυτούς συγκαταλέγονται και οι πολυμορφισμοί μονών νουκλεοτιδίων (SNP’s) που είναι μεταλλάξεις μίας μόνο βάσης και έχουν κατηγορηθεί ως επί το πλείστον για γονιδιακές παθήσεις μέσω των μονοπατίων μεθυλίωσης και των γονιδιακών αποσιωπήσεων. Στη παρούσα διατριβή θα μιλήσουμε για τους πολυμορφισμούς που υφίστανται σε μια ανεξερεύνητη, όσον αφορά την γονιμότητα, περιοχή του χρωμοσώματος 9 που κωδικοποιεί ένα μακρύ και μή κωδικοποιητικό RNA, το ANRIL το οποίο έχει βρεθεί ότι εκφράζεται ασυνήθιστα και παίζει σημαντικό ρόλο σε αρκετές παθήσεις συμπεριλαμβανομένης και της ενδομητρίωσης. Στόχος μας είναι να μελετήσουμε οποιαδήποτε συσχέτιση μπορεί να προκύψει μεταξύ των πολυμορφισμών αυτών, της γυναικείας υπογονιμότητας και την απάντησή τους στα πρωτόκολλα εξωσωματικής γονιμοποίησης.Polymorphisms are widely known as epigenetic mutations in the genome and are responsible for the uniqueness and diversity of species. These include single nucleotide polymorphisms (SNPs), which are single-base mutations and have been blamed mostly for genetic diseases through methylation pathways and gene silencing. In this study we will discuss about the polymorphisms that reside in an unexplored, in terms of fertility, region of chromosome 9 and encode a long non-coding RNA, named ANRIL which has been found to be abnormally expressed and plays an important role in several diseases including endometriosis. Our goal is to study any association that may occur between these polymorphisms, female infertility and their response to in vitro fertilization protocols

Isobutyryl-CoA dehydrogenase deficiency associated with autism in a girl without an alternative genetic diagnosis by trio whole exome sequencing: A case report

Background: Isobutyryl-CoA dehydrogenase (IBD) is a mitochondrial enzyme catalysing the third step in the degradation of the essential branched-chain amino acid valine and is encoded by ACAD8. ACAD8 mutations lead to isobutyryl-CoA dehydrogenase deficiency (IBDD), which is identified by increased C4-acylcarnitine levels. Affected individuals are either asymptomatic or display a variety of symptoms during infancy, including speech delay, cognitive impairment, failure to thrive, hypotonia, and emesis. Methods: Here, we review all previously published IBDD patients and describe a girl diagnosed with IBDD who was presenting with autism as the main disease feature. Results: To assess whether a phenotype-genotype correlation exists that could explain the development or absence of clinical symptoms in IBDD, we compared CADD scores, in silico mutation predictions, LoF tolerance scores and C4-acylcarnitine levels between symptomatic and asymptomatic individuals. Statistical analysis of these parameters did not establish significant differences amongst both groups. Conclusion: As in our proband, tri

NIS- and pendrin-autoantibodies as diagnostic markers in thyroid disease

Introduction: Iodine is an essential component in thyroid hormone biosynthesis. Iodide transport through thyrocytes is mainly mediated by the basolateral sodium-iodide-symporter (NIS, SLC5A5) and the apical anion exchanger pendrin (PDS, SLC26A4). The role of TPO- and TSH-receptor-autoantibodies in the pathogenesis and diagnosis of autoimmune thyroid disease is well established. However, reports regarding the prevalence and diagnostic utility of autoantibodies (aAb) against NIS and PDS have been contradictory, possibly due to small study groups and underlying methodological differences of the published papers. Methods: We established two novel non-radioactive assays using the full length antigens NIS und PDS. For this purpose, NIS and PDS were recombinantly expressed as fusion protein with firefly-luciferase in stably transfected HEK293 cells. Serum samples from a large cohort of 323 thyroid patients and 400 healthy controls were screened for NIS- and PDS-aAb. Results: Thyroid patients showed an approximately fourfold higher prevalence of NIS-aAb (7.7%) than controls (1.8%), while the prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs. 5.0%). The highest prevalence of NIS- and PDS-aAb was seen in the subgroup of Graves’ disease patients (12.3% and 11.0%, respectively). No correlation was found between the investigated aAb-titers and TPO-aAb or TSH-receptor-aAb or selenium or zinc status. The reproducibility of assay signals was verified with respect to linearity, stability and absence of matrix effects. Conclusions: The results are in agreement with recent studies. While a determination of PDS-aAb in thyroid patients does not yet seem to be of diagnostic value, a possible relevance of NIS-aAb for an improved diagnosis of thyroid disease was shown.Einleitung: Iod ist ein essentieller Bestandteil in der Schilddrüsenhormon-Biosynthese. Der Iodid-Transport durch die Thyreozyten erfolgt hauptsächlich durch den basolateralen Natrium-Iodid-Symporter (NIS, SLC5A5) und den apikalen Anionen-Austauscher Pendrin (PDS, SLC26A4). Die Rolle von TPO- und TSH Rezeptor-Autoantikörpern in der Pathogenese und Diagnostik von autoimmunbedingten Schilddrüsenerkrankungen ist gut etabliert. Widersprüchlich zeigen sich allerdings Berichte über die Prävalenz und den diagnostischen Nutzen von Autoantikörpern (aAk) gegen NIS und PDS; dies ist möglicherweise auf die kleinen Studiengruppen und methodische Unterschiede der publizierten Arbeiten zurückzuführen. Methoden: Es erfolgte die Etablierung zweier neuartiger nicht-radioaktiver Assays mit den Antigenen NIS und PDS in voller Länge. Dafür wurden NIS und PDS rekombinant als Fusionsprotein mit Firefly-Luciferase in stabil transfizierten HEK293-Zellen exprimiert. Hiermit wurden Serumproben einer großen Kohorte von 323 Schilddrüsenpatienten und 400 gesunden Kontrollen vermessen. Ergebnisse: Schilddrüsenpatienten zeigten eine ca. viermal höhere Prävalenz für NIS-aAk (7,7 %) als Kontrollen (1,8 %), während die Prävalenz von PDS-aAk bei Schilddrüsenpatienten und Kontrollen ähnlich war (7,7 % vs. 5,0 %). Die höchste Prävalenz von NIS- und PDS-aAk zeigte sich in der Subgruppe der M. Basedow Patienten (12,3 % und 11,0 %). Es zeigte sich keine Beziehung der untersuchten aAk zu den TPO aAk oder TSH-Rezeptor-aAk-Titern bzw. dem Selen- oder Zinkstatus. Die Reproduzierbarkeit der Assaysignale wurde hinsichtlich Linearität, Stabilität und Abwesenheit von Matrixeffekten verifiziert. Schlussfolgerungen: Die Ergebnisse stehen in Übereinstimmung mit aktuellen Studien. Während der Bestimmung von PDS-aAk bei Schilddrüsenpatienten derzeit kein diagnostischer Wert zukommt, zeigte sich eine mögliche Relevanz von NIS-aAk für eine verbesserte Diagnostik von Schilddrüsenerkrankungen

Immediate and Delayed Mortality of Four Stored-Product Pests on Concrete Surfaces Treated with Chlorantraniliprole

Chlorantraniliprole is an effective pesticide against a plethora of pests, but its efficacy against stored-product pests is very poorly explored. In this study we treated concrete surfaces with four different doses of chlorantraniliprole (0.01, 0.05, 0.1, and 0.5 mg a.i./cm2) against the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) adults and larvae, the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) adults, the rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae) adults, and the flour mite, Acarus siro L. (Sarcoptiformes: Acaridae) adults and nymphs, to examine the immediate mortalities after 1, 2, 3, 4, and 5 days of exposure. Additionally, the delayed mortality of the individuals that survived the 5-day exposure was also evaluated after a further 7 days on untreated concrete surfaces. We documented high mortality rates for all tested species and their developmental stages. After 5 days of exposure to 0.5 mg a.i./cm2, T. castaneum larvae and A. siro adults exhibited the highest immediate mortality levels, reaching 96.7% and 92.2%, respectively. Delayed mortality was also very high for all tested species and their developmental stages. Nymphs of A. siro displayed a 96.3% delayed mortality followed by the adults of R. dominica (98.6%) after exposure to 0.5 mg a.i./cm2. All other tested species and their developmental stages reached complete (100.0%) delayed mortality, where even 0.01 mg a.i./cm2 caused ≥86.6% delayed mortality in all species and their developmental stages. Taking into consideration the effectiveness of chlorantraniliprole on this wide range of noxious arthropods, coupled with its low toxicity towards beneficial arthropods and mammals, this pesticide could provide an effective management tool for stored-product pests in storage facilities

The glycemic status determines the direction of the relationship between red cell distribution width and HbA1c

Aims: Available studies conducted on heterogenous populations on the association between the erythrocyte distribution width (RDW) and HbA1c have reported a positive, negative or neutral relationship. The aim of the present study is to investigate the debated relationship between RDW and HbA1c among hematologically healthy individuals with and without type 2 diabetes mellitus (T2DM). Methods: Paired measurements of RDW and HbA1c of 183 hematologically healthy individuals (100 without DM, 83 with T2DM) were obtained. The association of HbA1c with a) hematologic parameters (hemoglobin, log [ferritin], RDW) and b) factors related to glycemia (BMI, fructosamine, FPG) was examined within each group separately and in the sum of the study sample. Results: There was a significant positive correlation of RDW with HbA1c among those without DM while the opposite was true among individuals with T2DM (r = -0.315, p = 0.001 and r = -0.275, p = 0.011). In the T2DM group a significant negative correlation with fructosamine was noted (r = -0.274, p = 0.012) which was absent among normoglycemic individuals. Among those without DM the association between HbA1c and RDW remained significant after adjustment for all tested parameters. In the population with T2DM the significance was attenuated after including glycemia-related factors values. In multivariable regression in the sum of the study sample, the interaction between diabetes status and RDW as regards HbA1c was significant [unstandardized correlation coefficient -0.397 (-0.646 to -0.147), p = 0.002] and remained significant after adjustment for multiple potential confounders. Conclusions: Among individuals without DM, the RDW likely reflects the non-glycemic interference on HbA1c values, while in T2DM RDW may serve as an indirect index of glycemia and dysmetabolism

Individualizing Therapy for Neovascular Age-Related Macular Degeneration with Aflibercept (VITAL): A Two-Year Prospective, Interventional Single-Centre Trial

Abstract Aims To report the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and reading performance (reading acuity and maximum reading speed (MRS) using the MNREAD test) between baseline and 24 months in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept injections. Methods A prospective, open-label, interventional non-randomised case series with 24 months’ duration. Patients were recruited to the study from medical retina clinics at Moorfields Eye Hospital. Intravitreal injections of 2.0 mg aflibercept in the study eye were administered using a fixed dosing regimen during the first year and a treat-and-extend treatment regimen during the second year of treatment. Results Fifty patients were enrolled with a mean age (SD) of 78.7 (7.6) years; a mean BCVA of 62.8 ETDRS letters; mean reading acuity of 0.52 logMAR; mean maximum reading speed (MRS) of 141.3 words per minute and a central macular thickness of 322.6 µm at baseline. The mean improvement in BCVA was 6.4 letters for the 44 patients (88%) for whom data was available at 2 years. The mean improvement in reading acuity was 0.13 logMAR with an improvement in MRS of 2.9 words per minute. The mean reduction in CRT from baseline was 104.8 µm. Conclusions Aflibercept treatment of nAMD using fixed dosing in year 1 and treat and extend in year 2 leads to improvements in reading ability, visual acuity and retinal morphology which were maintained to 2 years of treatment. Trial Registration ClinicalTrials.gov Identifier NCT02441816, the VITAL study

Three Year Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration: Evidence from a Clinical Setting

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