Investigation into the genetics of fetal congenital lymphatic anomalies

Objective

Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue edema, ascites, or hydrops. Many LAs are caused by single nucleotide variants, which are not detected on routine prenatal testing.

Methods

Demographic data were compared between two subcohorts, those with clinically significant fetal edema (CSFE) and isolated fetal edema. A targeted variant analysis of LA genes was performed using American College of Medical Genetics criteria on whole exome sequencing (WES) data generated for 71 fetal edema cases who remained undiagnosed after standard workup.

Results

CSFE cases had poor outcomes, including preterm delivery, demise, and maternal preeclampsia. Pathogenic and likely pathogenic variants were identified in 7% (5/71) of cases, including variants in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant. Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases. In CSFEs, VOUS were found in CELSR1, EPHB4, TIE1, PIEZO1, ITGA9, RASopathy genes, SOS1, SOS2, and RAF1.

Conclusions

WES identified pathogenic and likely pathogenic variants and VOUS in LA genes in 51% of fetal edema cases, supporting WES and expanded hydrops panels in cases of idiopathic fetal hydrops and fluid collections.     

The role of TAMMEF therapy on the antioxidant status in osteoarthritis

Osteoarthritis (OA) is the most common joint disorder, associated with loss of articular cartilage, osteophyte formation, subchodral bone change, synovitis and characterized by chronic and often disabling pain and stiffness of one or more joints. The pathogenesis of the disease is complex and still debated, even if recent studies have shown that reactive oxygen species may participate in the initiation and progression of OA. Moreover, it is known that pulsed electromagnetic fields are useful in the OA treatment, owing to their analgesic and anti-inflammatory properties. This work evaluated lipid peroxidation, glutathione, and ascorbic acid levels in patients with OA of spine, before and after the application of a new electromagnetic system, the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system. In TAMMEF system, the extremely low frequencies electromagnetic field is piloted by a musical signal and its parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges: so all possible codes can occur during a single application. Twenty patients affected by OA of spine and 20 healthy subjects were enrolled in this study. Plasma levels of ascorbic acid (AA), glutathione (GSH) and malondialdehyde (MDA) (as index of lipid peroxidation) were determined in patients and controls, before the beginning of treatment (first day of therapy) and at the end of cycle. All patients underwent a cycle of 10 daily sessions of 30 min each. Our study showed a significant increase of MDA level and a significant decrease of both AA and GSH levels in patients with OA compared to control group. These findings support the role of oxidative stress in the pathogenesis of OA. After TAMMEF treatment in the OA group, analysis revealed a significant decrease in plasma MDA and AA levels (P < 0.05 and P < 0.01, respectively), no significant difference in GSH levels. Reduction in MDA level could be due to the decreased generation of reactive oxygen species and/or to the increased detoxification activity mediated by GSH. No significant difference in GSH levels, evidenced in OA patients after TAMMEF treatment, could be due to effect sparing of AA on GSH. Furthermore, a beneficial symptomatic effect was observed in all patients.     

Sulphur, nitrogen and carbon content of Sphagnum capillifolium and Pseudevernia furfuracea exposed in bags in the Naples urban area

The accumulation ability of the major elements sulphur, nitrogen and carbon by the moss Sphagnum capillifolium (Ehrh.) Hedw. and the lichen Pseudevernia furfuracea (L.) Zopf exposed in bags in Naples urban area,was investigated. Bags were exposed at the beginning of July 1999 and gathered in two subsequent moments: at the end of the dry season (after 10 weeks of exposure) and during the wet season (after 17 weeks of exposure), to include the effects of rainy conditions. Sulphur and N content of the lichen increased all over the exposure period, while the level of C did not change significantly either after 10 or 17 weeks of exposition. For the moss the S accumulation was limited to the dry period of exposure, whereas N and C content decreased with exposure. Results, in contrast with those obtained in a previous study on trace elements bioaccumulation [Adamo et al., Environmental Pollution, (2003) 122, 91-103], suggest that accumulation of gaseous pollutants is strongly influenced by biomonitor vitality and that lichen bags are a more reliable and effective tool for monitoring S, N and C atmospheric depositions in urban areas compared to moss bags, because of greater lichen resistance to dry and stressing conditions of urban environment.     

Mixing Zone Characterization of Two Transition Terrain Streams With Tracers1

Abstract: For most wastewater discharges to streams, the effluent creates a plume that becomes less distinct as it mixes with the receiving water. Constant‐discharge tracer studies were used to characterize the plume or physical mixing zone (PMZ) at two similar transition terrain streams. At both sites, the laterally unmixed PMZs did not extend across the entire stream and mixing occurred relatively quickly. The observed plumes were significantly smaller than the regulatory mixing zone (RMZ) allowed by the State of Colorado. At Site 1 mixing occurred within a much shorter distance due to the presence of a riffle zone located a few meters downstream of the discharge point. Interpretation of field data with an analytical model suggests that the effective transverse dispersion coefficient (k_z) for the riffle zone at Site 1 (～1 m²/s) was significantly higher than the average value over the longer nonriffle section at Site 2 (～0.01 m²/s). These results imply that to achieve the fastest mixing in transition terrain streams, thereby minimizing the size of the PMZ, discharge outfalls should be located upstream and close to riffle zones.     

Potentially harmful elements in house dust from Estarreja,Portugal: characterization and genotoxicity of the bioaccessible fraction

Due to their behavioral characteristics, young children are vulnerable to the ingestion of indoor dust, often contaminated with chemicals that are potentially harmful. Exposure to potentially harmful elements (PHEs) is currently exacerbated by their widespread use in several industrial, agricultural, domestic and technological applications. PHEs cause adverse health effects on immune and nervous systems and can lead to cancer development via genotoxic mechanisms. The present study is an integrated approach that aims at assessing the genotoxicity of bioaccessible PHEs following ingestion of contaminated house dust. A multidisciplinary methodology associating chemical characterization of five house dust samples, extraction of the bioaccessible PHEs in gastric extracts by the unified BARGE method, determination of the bioaccessible fraction and in vitro genotoxicity of gastric extracts in adenocarcinoma gastric human (AGS) cells was developed. The five gastric extracts induced dose-dependent genotoxicity in AGS cells. Copper (bioaccessible concentration up to 111 mg/kg) was probably the prevalent PHE inducing primary DNA damage (up to 5.1-fold increase in tail DNA at 0.53 g/l of gastric extract). Lead (bioaccessible concentration up to 245 mg/kg) was the most prevalent PHE inducing chromosome-damaging effects (r = 0.55; p < 0.001 for micronucleated cells induction). The association of principal component analysis and Spearman’s correlations was decisive to understand the chromosome-damaging properties of the bioaccessible PHEs in AGS cells. This methodology could be used on a larger-scale study to provide useful information for science-based decision-making in regulatory policies, and a better estimation of human exposure and associated health risks.