Identification of a dna methylation episignature in the 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome‐wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Evaluation of a Fixed Spraying System for Phytosanitary Treatments in Heroic Viticulture in North-Eastern Italy

Modern viticulture cannot be practiced without the use of plant protection products to control diseases like downy mildew, powdery mildew, and pests. In severely sloping vineyards, where mechanization is not possible, pesticide application is realized using spray guns, which is a laborious, expensive, and dangerous application technique. In these vineyards, where viticulture is defined as “heroic viticulture,” vine-growers could seriously take advantage of innovation in spray-technique applications. For this reason, several prototypes of a fixed spraying system (FSS) were realized in recent years. Two prototypes of a fixed spraying system were built in 2019 in two different vineyards in the Veneto region (north-eastern Italy). In both vineyards, the fixed spraying systems were used to perform pesticide application during the 2020 season to control downy mildew, powdery mildew, and pests. With this solution, both vineyards were successfully protected, resulting in comparable infection degrees and yields as the ones protected with airblast sprayers and spray guns. This study contributes to assert fixed spraying systems as an innovation that could improve working conditions, safety, timing, and performances of plant protection products’ application in heroic viticulture areas

Ultrasound estimated fetal weight slightly below the median is associated with increased risk of spontaneous preterm birth

8noreservedBACKGROUND: This study investigates the possible relationship between ultrasound estimated fetal weight (EFW) at third trimester and the risk of preterm birth following spontaneous preterm labor in otherwise uncomplicated pregnancies. METHODS: We performed a nested case-control study including 281 cases of spontaneous preterm labor with preterm delivery in the third trimester and 3372 matched controls within a cohort of 6207 consecutive pregnant women. Pregnancies with fetal growth restriction (birth weight <10th centile of population-based normograms) or fetal anomalies were not included. EFW was calculated by using Hadlock's formula and converted to fetal gender adjusted multiples of median (MoM) for each gestational age. RESULTS: EFW correlated with birth weight (r = 0.959, p < 0.0001) and was lower in preterm than in control fetuses (p < 0.0001). The odds ratios (95% confidence intervals) for preterm birth for fetuses below 0.9 MoM, 0.85 MoM, 0.80 MoM, and 0.75 MoM of EFW were, respectively, 4.6 (3.6-5.9), 5.7 (4.3-7.5), 8.5 (5.9-12.1), and 11.2 (6.8-18.3). The independent relationship between preterm birth and lower EFW was confirmed in multivariate analysis with adjustment for potential confounders, such as maternal age, parity, and fetal gender. CONCLUSION: In asymptomatic women between 28 and 36 weeks of gestation, an EFW lower than 0.90 MoM increases by 4.6 times the risk of spontaneous preterm birth, and the risk increases proportionally to the degree of weight reductionmixedSeveri, F.M.;Bocchi, C.;Imperatore, A.;Boni, C.;Ferrata, C.;Florio, P.;Reis, F.M.;Petraglia, F.Severi, F. M.; Bocchi, C.; Imperatore, A.; Boni, C.; Ferrata, C.; Florio, P.; Reis, F. M.; Petraglia, F

Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage

Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats’ eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results

Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage

Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats’ eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results