Chemerin gene variants association with metabolic parameters in women with polycystic ovary syndrome

Objective: To evaluate Chemerin gene (RARRES2) SNVs rs4721 and rs17173608 association with clinical and biochemical characteristics, also with the metabolic and androgenic condition in women with Polycystic Ovary syndrome (PCOS).Materials and methods: We analyzed 107 women with PCOS according to the Rotterdam criteria (17-38 years). PCOS were divided into subgroups by the presence or absence of metabolicsyndrome (MS) and hyperandrogenism (HA). Peripheral blood genomic DNA was purified and genotyped by T-ARMS PCR (Tetraamplification refractory mutation system for rs 17173608 (RARRES2 NC_000007.14(NM_002889.4):c.280-494A>C) and PCR-RFLP for rs4721 (RARRES2 NM_002889.4):c.*13A>C). Statistical analyzes were performed with GraphPad Prism and SPSS (t-Student test,ANCOVA with p-values adjusted for age and χ2 analysis).Results: The PCOS patients showed a genotype distribution of TT genotype (44.9%), followed by TG genotype (43%) and GG (12.1%) for the rs4721; similar to the frequency found in Caucasians (Hap-MapProject). The population was in Hardy Weinberg equilibrium (x2= 0.147; p = 0.70). The rs17173608 could not be analyzed because of the low presence of the minor allele (4%). Through ANCOVA analysis age adjusted, it was shown that the presence of rs4721G allele was associated with higher levels of total cholesterol/HDL (p=0.04), LDL-c (p=0,02) triglycerides (p=0.03), insulin (p=0.02), HOMA (p=0.04), LAP index (Lipid accumulation product, p=0.03), testosterone (p= 0.08), LH/FSH (p=0.03). Also, rs4721 G allele was associated with larger telomere length (p=0.04) and lesser mitochondrial DNA mass (p=0.08).Conclusion: In women with PCOS, rs4721G allele was associated with worse metabolic and hormonal parameters. In this preliminary study, no association was found between SNV rs4721 Chemerin gene and susceptibility to MS and HA in women with PCOS.Fil: Velazquez, Mariela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Rojo, Mailen. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Pautasso, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Millán, Andrea Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Abruzzese, Giselle Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Motta, Alicia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Cerrone, Gloria Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de FisiologíaVirtualArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de Fisiologí

Telomere Length Differently Associated to Obesity and Hyperandrogenism in Women With Polycystic Ovary Syndrome

Background: Polycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL). Aims: To compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters. Materials and methods: The PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR. Results: Women with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp). Conclusions: Whilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.Fil: Velazquez, Mariela Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Millán, Andrea Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rojo, Mailén. Universidad de Buenos Aires; ArgentinaFil: Abruzzese, Giselle Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Cocucci, Silvina Ema. Universidad de Buenos Aires; ArgentinaFil: Iglesias Molli, Andrea Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Motta, Alicia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Cerrone, Gloria Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia

Recent genomic studies have identified a wide range of novel genetic alterations that have substantially increased our knowledge of the biology of B- and T-progenitor acute lymphoblastic leukaemia (B-ALL, T-ALL) and defined new subtypes with prognostic and therapeutic relevance.1-4 Thanks to the use of transcriptome sequencing approaches, new cryptic fusion transcripts have been described, such as the ATP5L-KMT2A gene fusion, described by Gestrich et al. in a 14-month-old patient with aggressive B-ALL.5 ATP5L or ATP5MG (ATP Synthase Membrane Subunit G) catalyzes ATP synthesis during oxidative phosphorylation.6 This protein has recently been reported to interact with a SARS-CoV-2 protein.7 The histone lysine [K]-methyl transferase 2A (KMT2A) gene is a transcriptional coactivator that plays an essential role in regulating gene expression during early development and haematopoiesis. It is frequently rearranged to over 135 translocation partner genes in acute leukaemias.8 ATP5L is a novel KMT2A fusion partner not detectable by fluorescent in situ hybridization (FISH) or karyotype, due to the closeness of the two genes on chromosome 11q23. The Cleveland Medical Centre team found a reciprocal out-of-frame ATP5L-KMT2A rearrangement that juxtaposes the ATP5L exon 1 to the KMT2A exon 2, with the insertion of an extra nucleotide (G) at the fusion site.5 We sequenced leukaemic cells from eight adult ALL patients (two T-ALL, five B-ALL Philadelphia negative (Ph−) and one B-ALL Ph+; Table I) by a 199 gene RNA-sequencing panel (RNA-seq; Pan-Heme FusionPlex, ArcherDx Inc., Boulder, CO, USA).The study was supported by European Union Seventh Framework Programme (FP7/2007-2013) (GA 306242-NGS-PTL) and Associazione Italiana Leucemie (AIL)

Patient-reported symptom monitoring and adherence to therapy in patients with newly diagnosed chronic myeloid leukemia

Background: The authors assessed the clinical utility of patient-reported symptom monitoring in the setting of newly diagnosed chronic myeloid leukemia (CML). The primary objective was to evaluate adherence to therapy. Methods: The authors conducted an international prospective study that included patients with newly diagnosed, chronic-phase CML. Before clinical consultation, patients were provided a tablet computer to self-rate their symptoms, and the results were available in real time to each physician during the patient's visit. Adherence was assessed by pill count and with a validated self-reported questionnaire. The proportions of optimal responders at 3 and 6 months were assessed according to the European LeukemiaNet criteria. Results: Between July 2020 and August 2021, 94 patients with a median age of 57 years were enrolled. Pill count adherence analysis indicated that 86 of 93 evaluable patients (92.5%) took at least 90% of prescribed tyrosine kinase inhibitor therapy during the 6-month observation period. The online platform was well accepted by patients and physicians. An optimal response was achieved by 69 of 79 patients (87.3%) at 3 months and by 61 of 81 patients (75.3%) at 6 months. Conclusions: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates (ClinicalTrials.gov identifier NCT04384848)

Prognostic Factors for Overall Survival In Chronic Myeloid Leukemia Patients: A Multicentric Cohort Study by the Italian CML GIMEMA Network

An observational prospective study was conducted by the CML Italian network to analyze the role of baseline patient characteristics and first line treatments on overall survival and CML-related mortality in 1206 newly diagnosed CML patients, 608 treated with imatinib (IMA) and 598 with 2nd generation tyrosine kinase inhibitors (2GTKI). IMA-treated patients were much older (median age 69 years, IQR 58-77) than the 2GTKI group (52, IQR 41-63) and had more comorbidities. Estimated 4-year overall survival of the entire cohort was 89% (95%CI 85.9-91.4). Overall, 73 patients (6.1%) died: 17 (2.8%) in the 2GTKI vs 56 (9.2%) in the IMA cohort (adjusted HR=0.50; 95% CI=0.26-0.94), but no differences were detected for CML-related mortality (10 (1.7%) vs 11 (1.8%) in the 2GTKIs vs IMA cohort (sHR=1.61; 0.52-4.96). The ELTS score was associated to CML mortality (high risk vs low, HR=9.67; 95%CI 2.94-31.74; p<0.001), while age (per year, HR=1.03; 95%CI 1.00-1.06; p=0.064), CCI (4-5 vs 2, HR=5.22; 95%CI 2.56-10.65; p<0.001), ELTS score (high risk vs low, HR=3.11; 95%CI 1.52-6.35, p=0.002) and 2GTKI vs IMA (HR=0.26; 95%CI 0.10-0.65, p=0.004) were associated to an increased risk of non-related CML mortality. The ELTS score showed a better discriminant ability than the Sokal score in all comparisons

Emergenza sismica nel centro Italia 2016-2017. Secondo rapporto del gruppo operativo SISMIKO. Sviluppo e mantenimento della rete sismica mobile a seguito del terremoto di Amatrice Mw 6.0 (24 agosto 2016, Italia centrale)

La rete sismica temporanea installata dal gruppo operativo INGV SISMIKO a seguito del terremoto del 24 agosto 2016 tra i Monti della Laga e la Valnerina, è stata ampliata nel settore settentrionale a seguito dei forti terremoti avvenuti alla fine del mese di ottobre 2016. Successivamente alle due scosse di Mw 5.4 e 5.9 che il 26 ottobre hanno interessato l’area al confine Marche-Umbria tra i Comuni di Castelsantangelo sul Nera (MC), Norcia (PG) e Arquata del Tronto (AP), la geometria della rete è stata estesa di circa 25 km verso nord con l’attivazione di ulteriori tre stazioni temporanee di cui una, da subito, disposta per la trasmissione dei dati in tempo reale e per l’inserimento nel sistema di sorveglianza sismica dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV). Un’ultima stazione è stata inoltre installata nei pressi di Campello del Clitunno in provincia di Perugia ad ovest della sequenza, a seguito del terremoto Mw 6.5 che la mattina del 30 ottobre ha interessato l’intera area già fortemente provata dalla sequenza in corso; questo è stato il più forte terremoto registrato negli ultimi 30 in Italia. A circa 5 mesi dall’inizio dell’emergenza sismica, la rete temporanea conta quindi 23 stazioni che da metà dicembre sono tutte trasmesse in tempo reale ai diversi centri di acquisizione INGV, ovvero Milano, Ancona e Grottaminarda ma soprattutto Roma dove i dati vengono contestualmente archiviati nell’European Integrated Data Archive (EIDA) e integrati nel sistema di monitoraggio e sorveglianza sismica dell’INGV; per la sorveglianza sono incluse solo parte delle stazioni. Nelle ultime settimane, le attività di campagna del gruppo operativo SISMIKO sono state costantemente focalizzate alla cura e alla manutenzione della strumentazione per garantire la continuità della trasmissione e dell’acquisizione dei dati, a volte compromesse da malfunzionamenti legati al maltempo. Alla data di aggiornamento del presente report, non è ancora stata decretata una dismissione o una rimodulazione della geometria della rete sismica temporanea, anche in considerazione della attività sismica in corso a tutt’oggi molto sostenuta. Tutti i dati acquisiti dalle stazioni temporanee SISMIKO, sono distribuiti senza alcun vincolo, al pari dei dati della Rete Sismica Nazionale (RSN, codice di rete IV), ed utilizzati per prodotti scientifici in tempo reale (localizzazioni di sala, calcolo dei Time Domain Moment Tensor -TDMT delle ShakeMaps, ecc) e per l’aggiornamento dei database dell’INGV come l’Italian Seismological Instrumental and Parametric Database (ISIDe) con la revisione del Bollettino Sismico Italiano (BSI), dell’INGV Strong Motion Data (ISMD) e dell’ITalian ACcelerometric Archive (ITACA), dell’European-Mediterranean Regional Centroid Moment Tensors (RCMT) e nei lavori scientifici che utilizzano forme d’onda velocimetriche ed accelerometriche (ri- localizzazioni, studi della sorgente sismica ecc.).Istituto Nazionale di Geofisica e Vulcanologia (INGV)Published1SR. TERREMOTI - Servizi e ricerca per la Societ

Rapporto Preliminare Sulle Attività Svolte Nel Primo Mese Di Emergenza Dal Gruppo Operativo Sismiko A Seguito Del Terremoto Di Amatrice Mw 6.0 (24 Agosto 2016, Italia Centrale)

Sintesi delle attività svolte dal coordinamento delle reti sismiche mobili INGV in emergenza, denominato SISMIKO, nel primo mese della sequenza sismica “Amatrice” seguita al terremoto di Mw 6.0 del 24 agosto 2016 (01:36 UTC). Descrizione della rete sismica implementata e prime analisi dei dati acquisiti. Report on the activities in the first month of emergency by coordination of mobile seismic networks INGV emergency, called SISMIKO, after the Mw 6.0 Amatrice earthquake (August 24th, 2016, central italy). Description of the temporary seismic network implemented and preliminary analysis of the acquired data.INGV DPCPublished1IT. Reti di monitoraggi

SISMIKO:emergency network deployment and data sharing for the 2016 central Italy seismic sequence

At 01:36 UTC (03:36 local time) on August 24th 2016, an earthquake Mw 6.0 struck an extensive sector of the central Apennines (coordinates: latitude 42.70° N, longitude 13.23° E, 8.0 km depth). The earthquake caused about 300 casualties and severe damage to the historical buildings and economic activity in an area located near the borders of the Umbria, Lazio, Abruzzo and Marche regions. The Istituto Nazionale di Geofisica e Vulcanologia (INGV) located in few minutes the hypocenter near Accumoli, a small town in the province of Rieti. In the hours after the quake, dozens of events were recorded by the National Seismic Network (Rete Sismica Nazionale, RSN) of the INGV, many of which had a ML > 3.0. The density and coverage of the RSN in the epicentral area meant the epicenter and magnitude of the main event and subsequent shocks that followed it in the early hours of the seismic sequence were well constrained. However, in order to better constrain the localizations of the aftershock hypocenters, especially the depths, a denser seismic monitoring network was needed. Just after the mainshock, SISMIKO, the coordinating body of the emergency seismic network at INGV, was activated in order to install a temporary seismic network integrated with the existing permanent network in the epicentral area. From August the 24th to the 30th, SISMIKO deployed eighteen seismic stations, generally six components (equipped with both velocimeter and accelerometer), with thirteen of the seismic station transmitting in real-time to the INGV seismic monitoring room in Rome. The design and geometry of the temporary network was decided in consolation with other groups who were deploying seismic stations in the region, namely EMERSITO (a group studying site-effects), and the emergency Italian strong motion network (RAN) managed by the National Civil Protection Department (DPC). Further 25 BB temporary seismic stations were deployed by colleagues of the British Geological Survey (BGS) and the School of Geosciences, University of Edinburgh in collaboration with INGV. All data acquired from SISMIKO stations, are quickly available at the European Integrated Data Archive (EIDA). The data acquired by the SISMIKO stations were included in the preliminary analysis that was performed by the Bollettino Sismico Italiano (BSI), the Centro Nazionale Terremoti (CNT) staff working in Ancona, and the INGV-MI, described below

Le attività del gruppo operativo INGV "SISMIKO" durante la sequenza sismica "Amatrice 2016",

SISMIKO è un gruppo operativo dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV) che coordina tutte le Reti Sismiche Mobili INGVPublishedLecce3T. Sorgente sismica4T. Sismicità dell'Italia8T. Sismologia in tempo reale1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunami2SR TERREMOTI - Gestione delle emergenze sismiche e da maremoto3SR TERREMOTI - Attività dei Centr