Mendelian Randomization using Public Data from Genetic Consortia.

Mendelian randomization (MR) is a technique that seeks to establish causation between an exposure and an outcome using observational data. It is an instrumental variable analysis in which genetic variants are used as the instruments. Many consortia have meta-analysed genome-wide associations between variants and specific traits and made their results publicly available. Using such data, it is possible to derive genetic risk scores for one trait and to deduce the association of that same risk score with a second trait. The properties of this approach are investigated by simulation and by evaluating the potentially causal effect of birth weight on adult glucose level. In such analyses, it is important to decide whether one is interested in the risk score based on a set of estimated regression coefficients or the score based on the true underlying coefficients. MR is primarily concerned with the latter. Methods designed for the former question will under-estimate the variance if used for MR. This variance can be corrected but it needs to be done with care to avoid introducing bias. MR based on public data sources is useful and easy to perform, but care must be taken to avoid false precision or bias

Hydrocortisone malabsorption due to polyethylene glycols (Macrogol 3350) in a girl with congenital adrenal insufficiency.

BACKGROUND: Primary adrenal insufficiency is relatively rare in children and, if unrecognized, may present with cardiovascular collapse, making it a potentially life-threatening entity. CASE PRESENTATION: The proposita, 11 months old of age, was admitted for lethargy and severe dehydration. Blood pressure was 62/38 mm Hg, and biochemical measurements showed hyponatraemia, hypochloraemia, hyperkalaemia, and metabolic acidaemia. Renin activity was 1484 μU/mL; cortisol, 1.03 μg/dL (normal, 5-25 μg/dL); and corticotropin (ACTH), 4832 ng/L (normal, 9-52 ng/L). Adrenal deficiency was diagnosed, and replacement therapy with glucocorticoids and mineralocorticoids was initiated. After 40 days, ACTH was 797 ng/L. During follow-up, the patient started taking macrogol twice daily for constipation and experienced a significant increase in ACTH (3262 ng/L), which dropped to 648 ng/L when macrogol was stopped. After arbitrary reintroduction of macrogol, the child presented with hypoglycaemia, lethargy, weakness, and hypotonia; ACTH was 3145 ng/L. After again stopping macrogol, her ACTH was near normalized (323 ng/L). CONCLUSION: Hydrocortisone malabsorption may be caused by macrogol use. Because chronic constipation is frequently reported in children, the possibility that macrogol contributes to adrenal crisis should be taken in account

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/thy.2020.0393

Space-time gravity variations to look deep into the southern flank of Etna volcano

A microgravity 14-year-long data set (October 1994 - September 2007) recorded along a 24-kilometer East-West trending profile of 19 stations was analyzed to detect underground mass redistributions related to the volcanic activity involving the southern flank of Mt Etna volcano (Italy). A multiresolution wavelet analysis was applied to separate the volcano-related signal from the unwanted components due to mainly instrumental, human-made and seasonal effects. The residual space-time image evidenced two complete gravity increase/decrease cycles mainly affecting the central and eastern stations of the profile. The first gravity increase (early-1995 to end-1996) – decrease (end-1996 to late-1998) cycle reached a maximum amplitude of approximately 90 µGal. The second gravity increase (mid-1999 to mid-2000) – decrease (mid-2000 to early-2004) cycle attained an amplitude of about 80 µGal peak-to-peak. After about five years of a persistent negative gravity anomaly, a new semi-cycle started at the end of 2006 and continued during the last survey carried out in September 2007. We modeled the 1994-2007 gravity anomalies using a Quadratic Programming algorithm to infer the position and the evolution of the sources beneath the profile. The computed positive mass variations of about 1.05 x 1011 kg were interpreted as magma accumulation, while negative mass changes of about -1.20 x 1011 kg could reflect either magma migration or opening of new voids by tectonic tensile stresses within a source volume, where tensional earthquakes occurred

Role of ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty replacement of the myocardium that represents the substrate for recurrent sustained ventricular tachycardia (VT). These arrhythmias characterize the clinical course of a sizeable proportion of patients and have significant implications for their quality of life and long-term prognosis. Antiarrhythmic drugs are often poorly tolerated and usually provide incomplete control of arrhythmia relapses. Catheter ablation is a potentially effective strategy to treat frequent VT episodes and ICD shocks in ARVC patients. The aims of this review are to discuss the electrophysiological and electroanatomic substrates of ventricular tachycardia in patients with ARVC and to analyze the role of catheter ablation in their management with particular reference to selection of patients, technical issues, potential complications and outcomes

Looking inside the Panarea Island (Aeolian Archipelago, Italy) by gravity and magnetic data

In this paper we show and discuss the results of gravity and magnetic surveys of Panarea Island and its archipelago. The most recent volcanic manifestation occurred in November 2002 with a shallow submarine gas eruption between the islets of Dattilo, Panarelli, Lisca Bianca, Bottaro and Lisca Nera. Currently, the activity of Panarea is monitored through a multidisciplinary study under the umbrella of the Italian Department of Civil Protection with the goal of defining the hazard of this area. With this aim, in May 2006 the first gravity and magnetic surveys of Panarea Island and its archipelago were performed. The offshore magnetic data were obtained using a marine magnetometer, a Geometrics G880, from the Istituto Idrografico dell Marina (IIM). Onshore and offshore magnetic data were integrated into an unique dataset for complete magnetic coverage of the study area. By using two micro-gravimeters (LaCoste & Romberg), gravity data were collected along tracks every 250 meters. The gravity dataset was processed using the standard method. A Bouguer reduction was applied to the free-air gravity dataset using a detailed digital elevation model of the island and the neighbouring sea after evaluation of the optimal Bouguer density to reduce the topographic effect. The result is a Bouguer anomaly map that shows lateral variations in density distribution and the relationships between the shallow volcanic/crustal features and tectonic lineaments. This evidence is also highlighted by the magnetic pattern, which suggests the importance of the youngest volcanic deposits with respect to the magnetic features of the island

Strong enhancement of extremely energetic proton production in central heavy ion collisions at intermediate energy

The energetic proton emission has been investigated as a function of the reaction centrality for the system 58Ni + 58Ni at 30A MeV. Extremely energetic protons (EpNN > 130 MeV) were measured and their multiplicity is found to increase almost quadratically with the number of participant nucleons thus indicating the onset of a mechanism beyond one and two-body dynamics.Comment: 5 pages, 2 figures, submitted to Physical Review Letter

Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

BACKGROUND: Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. PATIENTS AND METHODS: We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard®, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T(0) and after 1 year (T(1)). RESULTS: At T(1), the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p < 0.0001) in Arm A and from 2.23 to 1.99 (p < 0.05) in Arm B. Acanthosis nigricans was significantly reduced in Arm A (13.2% to 5.6%; p < 0.05), and glycosylated-haemoglobin levels were significantly reduced in Arms A (p < 0.005). The percentage of glucose-metabolism abnormalities was reduced, although not significantly. However, the HOMA-IR index was significantly reduced in Arms A (p < 0.0001) and B (p < 0.05), with Arm A showing a significant reduction in the insulinogenic index (p < 0.05). Finally, the disposition index was significantly improved in Arms A (p < 0.0001) and B (p < 0.05). CONCLUSIONS: A LGI diet, particularly associated with the use of Policaptil Gel Retard®, may reduce weight gain and ameliorate the metabolic syndrome and insulin-resistance parameters in obese children and adolescents with family history of obesity and T2DM

Autosomal Recessive Atrial Dilated Cardiomyopathy With Standstill Evolution Associated With Mutation of Natriuretic Peptide Precursor A

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