Case Report: Whole Exome Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient With Autism Spectrum Disorder, Intellectual Disability, Hyperactivity, Sleep and Gastrointestinal Disturbances

Autism Spectrum Disorder (ASD) refers to a broad range of conditions characterized by difficulties in communication, social interaction and behavior, and may be accompanied by other medical or psychiatric conditions. Patients with ASD and comorbidities are often difficult to diagnose because of the tendency to consider the multiple symptoms as the presentation of a complicated syndromic form. This view influences variant filtering which might ignore causative variants for specific clinical features shown by the patient. Here we report on a male child diagnosed with ASD, showing cognitive and motor impairments, stereotypies, hyperactivity, sleep, and gastrointestinal disturbances. The analysis of whole exome sequencing (WES) data with bioinformatic tools for oligogenic diseases helped us to identify two major previously unreported pathogenetic variants: a maternally inherited missense variant (p.R4122H) in HUWE1, an ubiquitin protein ligase associated to X-linked intellectual disability and ASD; and a de novo stop variant (p.Q259X) in TPH2, encoding the tryptophan hydroxylase 2 enzyme involved in serotonin synthesis and associated with susceptibility to attention deficit-hyperactivity disorder (ADHD). TPH2, expressed in central and peripheral nervous tissues, modulates various physiological functions, including gut motility and sleep. To the best of our knowledge, this is the first case presenting with ASD, cognitive impairment, sleep, and gastrointestinal disturbances linked to both HUWE1 and TPH2 genes. Our findings could contribute to the existing knowledge on clinical and genetic diagnosis of patients with ASD presentation with comorbidities

Correlates of HCV seropositivity among familial contacts of HCV positive patients

BACKGROUND: Determinants of intrafamilial HCV transmission are still being debated. The aim of this study is to investigate the correlates of HCV seropositivity among familial contacts of HCV positive patients in Italy. METHODS: A cross-sectional study was conducted with 175 HCV positive patients (index cases), recruited from Policlinico Gemelli in Rome as well as other hospitals in Central Italy between 1995 and 2000 (40% female, mean age 57 ± 15.2 years), and 259 familial contacts. Differences in proportions of qualitative variables were tested with non-parametric tests (χ(2), Yates correction, Fisher exact test), and a p value < 0.05 was considered significant. A multivariate analysis was conducted using logistic regression in order to verify which variables statistically have an influence on HCV positivity in contact individuals. RESULTS: Seropositivity for HCV was found in 8.9% of the contacts. From the univariate analysis, risk factors significantly associated to HCV positivity in the contacts were: intravenous drug addiction (p = 0.004) and intercourse with drug addicts (p = 0.005). The only variables associated significantly and independently to HCV seropositivity in patients' contacts were intercourse with drug addicts (OR = 19.28; 95% CI: 2.01 – 184.94), the retirement status from work (OR = 3.76; 95% CI: 1.17 – 11.98), the time of the relationship (OR = 1.06; 95% CI: 1.00 – 1.11) and tattoos (OR = 7.68; 95% CI: 1.00 – 60.20). CONCLUSION: The present study confirms that having intercourse with a drug addict is the most significant risk factor for intrafamilial HCV transmission. The association with retirement status from work could be related to both a long-term relationship with an index case and past exposure to common risk factors

Sustainable irrigation strategy in fruit orchards: environmental impact at farm scale

Climate change is gradually affecting regional and global food production. Warming temperatures and a greater incidence and intensity of extreme weather events may lead to significant reductions in crop yields. The LIFE AgroClimaWater project provides adaptation strategies to increase water productivity in fruit orchards, reducing pollution and resource use. Experimental trials were conducted in fruit orchards of citrus, peach and olive, that were divided into two plots: one managed with sustainable practices (no soil tillage, compost addition, mulching of pruning residues, cover crops and guided irrigation through optimized water balance, reduced Kc and monitoring of soil moisture) and another one traditionally managed (weeding, empirical addition of mineral fertilizers and empirical irrigation). Effectiveness of cultivation practices applied in sustainable plots was assessed by Water Productivity (WP), Water Footprint (WF), Nutrient Use Efficiency (NUE); these parameters and indicators were compared to conventionally managed plots. Results revealed that the sustainable management leads to a maximum decrease of 11.64% in the WF, an increase in the WP till 13.28% and a nitrogen use efficiency (NUE) greater than 3 times in the sustainable orchard compared to the conventional one. The adoption of optimized irrigation management at farm scale, if properly adopted, could reduce the environmental impact at territorial level, increasing fruit quality and water productivity, with beneficial effect on natural resources (soil and water) conservation and restoration

Sustainable irrigation strategy in fruit orchards: environmental impact at farm scale

Climate change is gradually affecting regional and global food production. Warming temperatures and a greater incidence and intensity of extreme weather events may lead to significant reductions in crop yields. The LIFE AgroClimaWater project provides adaptation strategies to increase water productivity in fruit orchards, reducing pollution and resource use. Experimental trials were conducted in fruit orchards of citrus, peach and olive, that were divided into two plots: one managed with sustainable practices (no soil tillage, compost addition, mulching of pruning residues, cover crops and guided irrigation through optimized water balance, reduced Kc and monitoring of soil moisture) and another one traditionally managed (weeding, empirical addition of mineral fertilizers and empirical irrigation). Effectiveness of cultivation practices applied in sustainable plots was assessed by water productivity (WP), water footprint (WF), nutrient use efficiency (NUE); these parameters and indicators were compared to conventionally managed plots. Results revealed that the sustainable management leads to a maximum decrease of 11.64% in the WF, an increase in the WP till 13.28% and a nitrogen use efficiency (NUE) greater than 3 times in the sustainable orchard compared to the conventional one. The adoption of optimized irrigation management at farm scale, if properly adopted, could reduce the environmental impact at territorial level, increasing fruit quality and water productivity, with beneficial effect on natural resources (soil and water) conservation and restoration

LIFE AgroClimaWater project: environmental impact and water use of sustainable fruit orchards in Mediterranean area

Climate change is gradually affecting regional and global food production. Warming temperatures and intensity of extreme weather events may lead to significant reductions in crop yields. The LIFE AgroClimaWater project provides adaptation management strategies to increase water productivity in fruit orchards, reducing pollution and resource use. The increase of water use efficiency was achieved through a sustainable irrigation strategy based on the integration of the daily soil water balance with soil moisture measurements (from 0 to 90 cm depth). The monitoring of the soil profile contributes to optimize irrigation volumes, avoiding nutrient loss and percolation in the deep layers. The experimental sites of fruit orchards have been divided into two plots: one managed with sustainable practices (no-tillage, supply of organic fertilisers, mulching of pruning residues, cover crops and guided irrigation, controlled water stress) and another one conventionally managed (weeding, distribution of mineral fertilizers, empirical irrigation). Effectiveness of good agricultural practices (GAPs) applied in sustainable plots was assessed by performance indicators as Water Use Efficiency (WUE), Water Footprint (WF), Nutrient Use Efficiency (NUE) that were compared to conventionally managed plots. Results revealed that the sustainable irrigation strategy leads to a more than 30.0% decrease in the WF, a more than 20.0% increase in the WUE and a nitrogen use efficiency (NUEN) greater than 1.5 times in the sustainable orchards compared to that conventional ones. Moreover, the sustainable management has a beneficial effect on natural resources (soil and water) conservation and restoration, implementing the water productivity of the agro-ecosystem and highlighting the mitigation role of agro-ecosystems