The increasing consumption of pharmaceuticals, alongside their limited removal in wastewater treatment plants (WWTPs), have led to their ubiquitous occurrence in receiving aquatic environments. This ...study addresses the occurrence of 68 pharmaceuticals (PhACs) in the Ebro River Delta region (NE Spain), as well as their distribution in different environmental compartments, including surface water, sediments, biota (river biofilm and fish tissues), and field-collected plastic litter. In addition, their concentrations in serving WWTPs, as possible sources of environmental contamination, were also determined.
Our study confirmed the widespread occurrence of PhACs in riverine and, to a more limited extent, coastal environments. Most frequently detected PhACs belonged to analgesics/anti-inflammatories (e.g., ibuprofen) and psychiatric drugs (e.g., venlafaxine) therapeutic groups, followed by antihypertensives (e.g., valsartan) and antibiotics (e.g., azithromycin). Seasonal differences in cumulative levels of PhACs were reported for water and sediments (winter>summer). Despite spatial gradients were not clear along the river, a non-negligible contribution of upstream Ebro sites (reference area) was highlighted, which was unexpected based on the low anthropogenic pressure. Sediments represented a minor attenuation pathway for the selected PhACs, whereas they were more heavily accumulated in biota: fish liver (up to 166 ng/g dw), river biofilms (up to 108 ng/g dw), fish plasma (up to 63 ng/mL), and fish muscle (up to 31 ng/g dw).
These findings highlight the importance of biomonitoring in the characterization of polluted areas and prioritization of hazardous substances (e.g., psychiatric drugs) in aquatic systems, and a particular interest of fish plasma as non-destructive biomonitoring matrix. PhACs were also detected on plastic litter, demonstrating their role as environmental sinks for certain PhACs (e.g., analgesics/anti-inflammatories, psychiatric drugs). Overall, the widespread detection of PhACs in a variety of biotic and abiotic matrices from the lower Ebro River and Delta warns about their possible environmental implications.
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•No geographical variation in pharmaceutical pollution along lower Ebro River basin.•Analgesics/anti-inflammatories, psychiatric drugs and antihypertensives as most frequent in river water•Biomonitoring improves assessment of pharmaceutical contamination compared to grab water.•River biofilm, fish plasma (non-destructive) and liver more informative than fish muscle•Plastic litter as a passive sink of some pharmaceuticals
The world population is experiencing colossal growth and thus demand for food, leading to an increase in the use of pesticides. Persistent pesticide contamination, such as carbendazim, remains a ...pressing environmental concern, with potentially long-term impacts on aquatic ecosystems. In the present study, Daphnia magna was exposed to carbendazim (5 µg L−1) for 12 generations, with the aim of assessing gene transcription alterations induced by carbendazim (using a D. magna custom microarray). The results showed that carbendazim caused changes in genes involved in the response to stress, DNA replication/repair, neurotransmission, ATP production, and lipid and carbohydrate metabolism at concentrations already found in the environment. These outcomes support the results of previous studies, in which carbendazim induced genotoxic effects and reproduction impairment (increasing the number of aborted eggs with the decreasing number of neonates produced). The exposure of daphnids to carbendazim did not cause a stable change in gene transcription between generations, with more genes being differentially expressed in the F0 generation than in the F12 generation. This could show some possible daphnid acclimation after 12 generations and is aligned with previous multigenerational studies where few ecotoxicological effects at the individual and populational levels and other subcellular level effects (e.g., biochemical biomarkers) were found.
The study aimed to assess the occurrence and the environmental risk of a group of 51 selected pesticides in the Guadiana Basin (a biodiversity hotspot, in the Mediterranean). The most abundant ...pesticides were bentazone and 2,4-D, while terbuthylazine together with terbutryn constituted the most ubiquitous pesticides. Eighteen out of the 38 pesticides detected are no longer approved in Europe, and 5 of them are included in the list of priority substances. The risk assessment showed that azinphos ethyl, diflufenican, irganol, imidacloprid, and oxadiazon occurred occasionally, but always in concentrations above their respective ecotoxicological threshold value. Contrary, bentazone, terbuthylazine, and terbutryn presented a high risk in most of the sampled locations and periods.
The site-specific risk assessment showed a spatial and temporal pattern, with a higher risk occurring mainly in intermittent streams, in the drought period. The presence of pesticides banned from the EU market since 2009 showed the importance of improving the monitoring process, to identify the main sources of pollution and the fate of these emerging compounds. The results showed the need of implementing actions to improve the sustainable use of pesticides in agricultural areas, working with farmers and management entities to reduce the contamination of aquatic ecosystems. Transboundary water governance is also required to solve potential transboundary contamination problems.
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•Drought enhanced the impact of pesticides in the ecosystems of Guadiana Basin.•Quantified 23 European banned pesticides in the Guadiana Basin.•Of the 38 pesticides detected, 32 may have induced risk to aquatic species.•Bentazone, Terbutryn, Terbuthylazine, Chlorfenvinphos, Diazinon with high risk•Greater risk in the streams of the Guadiana Basin than in the Alqueva reservoir
Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion ...channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains.
FMDV nonstructural protein 2B is able to insert itself into cellular membranes to form a pore. This pore allows the passage of ions and small molecules through the membrane. In this study, we were able to show that both current and small molecules are able to pass though the pore made by 2B. We also discovered for the first time a virus with a pore-forming protein that contains two independent functional pores. By making mutations in our infectious clone of FMDV, we determined that mutations in either pore resulted in nonviable virus. This suggests that both pore-forming functions are independently required during FMDV infection.
The ion selectivity of a channel can be quantified in several ways by using different experimental protocols. A wide, mesoscopic channel, the OmpF porin of the outer membrane of E. coli, serves as a ...case study for comparing and analysing several measures of the channel cation-anion permeability in chlorides of alkali metals (LiCl, NaCl, KCl, CsCl). We show how different insights can be gained and integrated to rationalize the global image of channel selectivity. To this end, reversal potential, channel conductance and bi-ionic potential (two different salts with a common anion on each side of the channel but with the same concentration) experiments are discussed in light of an electrodiffusion model based on the Poisson-Nernst-Planck formalism. Measurements and calculations based on the atomic crystal structure of the channel show that each protocol displays a particular balance between the different sources of selectivity.
The world population is experiencing colossal growth and thus demand for food, leading to an increase in the use of pesticides. Persistent pesticide contamination, such as carbendazim, remains a ...pressing environmental concern, with potentially long-term impacts on aquatic ecosystems. In the present study, Daphnia magna was exposed to carbendazim (5 µg Lsup.−1 ) for 12 generations, with the aim of assessing gene transcription alterations induced by carbendazim (using a D. magna custom microarray). The results showed that carbendazim caused changes in genes involved in the response to stress, DNA replication/repair, neurotransmission, ATP production, and lipid and carbohydrate metabolism at concentrations already found in the environment. These outcomes support the results of previous studies, in which carbendazim induced genotoxic effects and reproduction impairment (increasing the number of aborted eggs with the decreasing number of neonates produced). The exposure of daphnids to carbendazim did not cause a stable change in gene transcription between generations, with more genes being differentially expressed in the F0 generation than in the F12 generation. This could show some possible daphnid acclimation after 12 generations and is aligned with previous multigenerational studies where few ecotoxicological effects at the individual and populational levels and other subcellular level effects (e.g., biochemical biomarkers) were found.
Background
Compared with peers, young sexual and gender minorities (SGM) are at a four to seven-fold increased risk of attempting suicide. Prior epidemiological studies, mainly focusing on monomorbid ...inequalities and without conducting diagnostic clinical interviews, have been unable to report robust data on psychiatric comorbidities among those who attempted suicide. The purpose of this presentation is to describe the presence of current psychiatric comorbidities among SGM youth and young adults at elevated risk for repeat suicide attempts.
Methods
A diverse convenience sample of SGM youth and young adults with a lifetime history of suicide attempts and current suicidal ideation was recruited for an open-phase suicide prevention trial in San Diego, CA. At baseline, participants underwent a 15-module DIAMOND interview for adults or computerized K-SADS for minors, and a battery of self-report questionnaires.
Results
Among the 31 participants (Mage = 22 years Range: 16, 29; 100% sexual, 52% gender, and 61% racial/ethnic minority), 27 (87%) participants met criteria for any mood disorder, 24 (77%) for any anxiety disorder, 16 (52%) for any trauma or stress disorder, and 2 (6%) for any psychotic disorder. One (3%) participant did not meet criteria for any psychiatric diagnoses, while five (16%) met criteria for a single and 25 (81%) for multiple diagnoses. The average number of diagnoses was 3.2 (Range: 0, 7). Additionally, 20 (65%) participants met the cut-off for likely ADHD, 20 (65%) for possible borderline personality disorder, and 21 (68%) for likely body dysmorphic disorder, with 11 (35%) within the 90th percentile for reference eating disorder severity.
Conclusions
The degree of psychiatric comorbidities in the sample of SGM youth and young adults at elevated risk for suicide was high. Beside direct suicide risk mitigation efforts, suicide prevention programs that target young SGM with a history of attempts should screen for untreated psychiatric disorders.
Key messages
* LGBTQ+ youth and young adults at elevated risk for repeat suicide attempts experience a high degree of psychiatric comorbity.
* Beyond suicide risk mitigation, LGBTQ+ youth suicide prevention programs should focus on untreated psychiatric comorbidities.
Although the crystallographic structure of the bacterial porin OmpF has been known for a decade, the physical mechanisms of its ionic selectivity are still under investigation. We address this issue ...in a series of experiments with varied pH, salt concentrations, inverted salt gradient, and charged and uncharged lipids. Measuring reversal potential, we show that OmpF selectivity (traditionally regarded as slightly cationic) depends strongly on pH and salt concentration and is conditionally asymmetric, that is, the calculated selectivity is sensitive to the direction of salt concentration gradient. At neutral pH and subdecimolar salt concentrations the channel exhibits nearly ideal cation selectivity
(
t
G
+
=
0.98
±
0.01
)
. Substituting neutral DPhPC with DPhPS, we demonstrate that the fixed charge of the host lipid has a small but measurable effect on the channel reversal potential. The available structural information allows for a qualitative explanation of our experimental findings. These findings now lead us to re-examine the ionization state of 102 titratable sites of the OmpF channel. Using standard methods of continuum electrostatics tailored to our particular purpose, we find the charge distribution in the channel as a function of solution acidity and relate the pH-dependent asymmetry in channel selectivity to the pH-dependent asymmetry in charge distribution. In an attempt to find a simple phenomenological description of our results, we also discuss different macroscopic models of electrodiffusion through large channels.
Abstract
Background
It has been suggested that the transition of patients from paediatric to adult care units may be key in the outcomes of inflammatory bowel disease (IBD). However, the impact of ...transition in real clinical practice has been barely studied. Aims: Principal: to evaluate the impact of transition on clinical outcomes in IBD. Secondary: to describe the prevalence of transition programs in Spain; to identify predictive factors of poor clinical outcomes; and to evaluate the percentage of patients with loss to follow-up.
Methods
Multicenter, retrospective, and observational study of IBD patients transferred between 2017-2020. Two groups (transition/no-transition) were compared retrospectively. Transition was defined as a structured process with at least 1 join visit involving the gastroenterologist, paediatrician, and a program coordinator, as well as the parents and the patient. Outcomes within the first 12 months after transfer were analysed. The main variable was the presence of “poor clinical outcome” defined as an IBD flare, hospitalisation, surgery or any change of the treatment due to an IBD flare. Predictive factors of poor clinical outcome were identified in multivariate analysis.
Results
A total of 278 patients from 34 Spanish hospitals were included: 185 patients (67%) from 22 hospitals (65%) performed a structured transition. In hospitals without transition, 91% of the patients were transferred to an IBD-specialist. In 66% of the patients in the transition group, 1 joint visit was performed. The median age of transfer was 16 years interquartile range (IQR)=12-20. Baseline characteristics of both groups are detailed in Figure 1.
At 1-year after transfer, hospitalisations and corticosteroid treatment were more frequent in the no-transition group (10 vs. 3%; p=0.025; 16 vs. 5%; p=0.002). At 1-year after transfer, 89 patients (27% transition vs. 43% no-transition; p=0.005) had poor clinical outcome median time: 9.3 months; 95% confidence interval (CI)=8.4-10.1 in no-transition; 10.4 months (95%CI 9.9-10.9) in the transition group. In the multivariate analysis, the lack of transition Hazard Ratio (HR)=2.1; 95%CI=1.4-3.3, IBD activity at transfer (HR=4.9; 95%CI=3.1-7.9), BMI <18.5 (HR=1.9; 95%CI=1.1-3.2) and corticosteroid treatment at transfer (HR=4.8; 95%CI=2.1-10.9) were associated with a poor clinical outcome. Twelve patients (4%) were lost to follow-up 1.1% in the no-transition vs. 5.9% in the transition group (p=0.06).
Conclusion
In the present study, to our knowledge the largest performed so far, the benefit of paediatric to adult transition program on patients’ outcomes has been demonstrated. The importance of achieving remission before transfer has also been highlighted.
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