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Background and Study Aims: There is an increasing trend to inappropriately prescribe proton pump inhibitors (PPIs) in different clinical settings despite the reported adverse outcomes. This study aimed to assess (1) the prevalence of potentially inappropriate use of PPIs and its associated risk factors among hospitalized patients, at pre-admission and discharge and (2) the prevalence of valid indications of PPIs use without prescription., Patients and Methods: A retrospective observational study was performed at a single center, examining the records of patients aged ≥18 years who were admitted to the Family Medicine inpatient service over a one-year period. The appropriateness of PPIs use was assessed against a set of pre-approved indications., Results: A total of 289 patients were included in the analysis. Of these, 34.67 % were taking PPIs upon admission, increasing to 43.67 % at discharge (p < 0.001). Inappropriate PPI use was identified in 51.92 % at pre-admission and 57.25 % at discharge. Multivariate analysis identified significant factors contributing to inappropriate PPI use: polypharmacy at both admission and discharge (OR = 4.587, p = 0.031), and the presence of two or more comorbidities at discharge (OR = 5.421, p = 0.011; OR = 13.005, p = 0.037). Age ≤65 was associated with increased inappropriate use only at discharge (p < 0.003). Conversely, appropriate prescribing was noted in patients over 65 and those on antiplatelet therapy, aligning with clinical guidelines., Conclusions: This study reveals a high prevalence of inappropriate PPI use among hospitalized patients, notably increasing from admission to discharge. Key contributors to inappropriate PPI usage included polypharmacy and high comorbidity scores at discharge, particularly in patients under 65. This emphasizes the need for targeted interventions to optimize PPI prescribing practices in clinical settings., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Rare earth elements (REE) are essential components of many electronic devices that could end-up in solid waste disposal sites and inadvertently released in the environment. The purpose of this study was to examine the toxicity of two heavy REEs, erbium (Er) and lutetium (Lu), in freshwater mussels Dreissena polymorpha. Mussels were exposed to 14 days to increasing concentration (10, 50, 250, and 1250 µg/L) of either Er and Lu at 15 °C and analyzed for gene expression in catalase (CAT), superoxide dismutase (SOD), metallothionein (MT), cytochrome c oxidase (CO1), and cyclin D for cell cycle. In addition, lipid peroxidation (LPO), DNA damage (DNAd), and arachidonate cyclooxygenase were also determined. The data revealed that mussels accumulated Er and Lu similarly and both REEs induced changes in mitochondrial COI activity. Er increased cell division, MT, and LPO, while Lu increased DNAd and decreased cell division. Tissue levels of Er were related to changes in MT (r = 0.7), LPO (r = 0.42), CO1 (r = 0.69), and CycD (r = 0.31). Lu tissue levels were related to changes in CO1 (r = 0.73), CycD (r =  - 0.61), CAT (r = 0.31), DNAd (r = 0.43), and SOD (r = 0.34). Although the lethal threshold was similar between Er and Lu, the threshold response for LPO revealed that Er produced toxicity at concentrations 25 times lower than Lu suggesting that Er was more harmful than Lu in mussels. In conclusions, the data supports that the toxicity pattern differed between Er and Lu although they are accumulated in the same fashion., (© 2024. Crown.)

Background: Previously, we reported that recovery-like behavior decreases stimulus control over drinking, and this likely plays a role in the clinical observation that longer recovery increases relapse resistance. Those studies were conducted using a procedure that required repeated assessment, preventing a longitudinal analysis of the changes in stimulus control over time in each individual. Here we recapitulate those results and extend them to female rats using a more efficient procedure that allows repeated assessment of changes in stimulus control over drinking during recovery., Methods: Under a multiple concurrent schedule, rats were trained to reliably respond predominantly for ethanol (concurrent Ethanol FR5, Food FR150) in the presence of one stimulus and for food (concurrent Ethanol FR5, Food FR5) in the presence of another stimulus. Stimuli were either lights or tones, depending on the group. After that, a drinking phase in which only the stimulus occasioning ethanol responding was presented (10 or 20 sessions) followed by recovery-like sessions in which only the stimulus occasioning food responding was presented. During these sessions, rats were exposed to the ethanol stimulus under extinction during the first component on sessions 0, 1, 2, 4, 8, and 16. The number of food responses during these stimulus exposures prior to the first five ethanol responses was the primary measure., Results: Consistent with the earlier procedure, the number of food responses during ethanol tests increased as a function of the number of recovery sessions completed, regardless of whether the stimuli were visual or auditory. However, there were no significant effects of extended alcohol exposure or sex., Conclusions: A rapid procedure consistent with the earlier procedure and clinical evidence was developed in which stimulus control over drinking decreased following longer periods of recovery. Under conditions tested, stimulus type, length of drinking history, and sex did not affect this relationship., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Periods of engaging in an alternative behavior diminishes behavioral control by stimuli occasioning alcohol use. This increase in relapse resistance with increasing recovery suggests that changing stimulus control over substance use may be a mechanism responsible for decreased relapse rates with longer recovery. However, the generality of this phenomenon to other drugs of abuse, including opioid self-administration, remains unclear. This study tests the generality of these findings with etonitazene to determine whether the shift in attention represents a behavioral process that generalizes from conditions we previously reported., Methods: Five adult male Lewis rats were trained to respond on levers under two stimulus conditions; high-cost food (food FR150 and etonitazene FR5) and low-cost food (both food and etonitazene FR 5). Next, only the high-cost food stimulus (occasioning etonitazene responding) was presented for 20 sessions (Use Phase) followed by 9 sessions in which only the low-cost food stimulus (occasioning food responding) was presented (Recovery Phase). During the Recovery Phase, testing occurred during the first component of sessions 0, 1, 2, 4, and 8 when rats were re-exposed to the high-cost food stimulus. The number of food responses prior to completing the etonitazene response requirement during this stimulus exposure was the primary measure., Results: Food responses during stimulus re-exposure increased significantly as a function of recovery sessions completed with a slope [95 % CI] of 2.49 responses/recovery session [0.16, 4.81]. The average number of etonitazene deliveries per use session was 32 ± 6.6 or an average daily dose of 48.8 ± 10.1 μg/kg. During Recovery Phase, etonitazene deliveries decreased to 2.4 ± 1 or 3.6 ± 1.5 μg/kg., Conclusion: The decrease in stimulus control observed for ethanol self-administration appears to generalize to opioid self-administration, indicating this change in stimulus control may play a general role in recovery., (Copyright © 2023. Published by Elsevier Inc.)

The influence of Pavlovian Conditioned Stimuli (CS) on ethanol self-administration and choice between ethanol and an alternative are potentially important. Ethanol-paired CS might increase ethanol self-administration, especially when it has been reduced during recovery, though the selectivity of these increases has been questioned. To date, one study examined the effects of an ethanol-paired CS on ethanol choice and found that the CS increased ethanol-responding more than food-responding when both were in extinction. However, it remains unclear whether ethanol-paired CS increase ethanol-choice that is not in extinction. Here, we examine the effects of an ethanol-paired CS on ethanol-choice when both food- and ethanol-responding are reinforced. Sixteen adult male Lewis rats were trained on a concurrent schedule to respond for ethanol on one lever and for food on the other lever. Ethanol was available under an FR 5 schedule, and food was available under an FR schedule that was adjusted for each rat to earn an equal number of food and ethanol deliveries. Then, 2-min light presentations were paired with an RT 25-sec schedule of ethanol delivery for 10 sessions in the absence of both levers. After this, subjects were placed back on the concurrent schedule for one session, then five sessions with the CS being present or absent on each trial of the concurrent schedule occurred. Rats learned to respond on one lever for ethanol and on the other for food and earned similar numbers of ethanol and food deliveries. During Pavlovian Conditioning, the number of head entries into the head-entry detector was higher in the presence of the CS than in its absence. In the test sessions, rats made more ethanol responses in the presence of the CS than in its absence. However, this effect was small and did not increase the amount of ethanol earned. Thus, ethanol-paired CS could increase ethanol-responding under a choice procedure but did not increase ethanol consumption meaningfully under the studied conditions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rare earth elements (REEs) are considered critical elements for technology and their extraction through mining activities is expected to increase in the future. Due to their chemical similarities, they often co-occur in minerals and thus their ecotoxicity should be assessed as a group/family. However, the available ecotoxicological studies focused mainly on the evaluation of the potential toxicological impacts of individual REEs rather than their mixtures. The aim of this study was therefore to evaluate the toxicity of a representative mixture of five REEs (La, Ce, Pr, Nd and Sm) spanning environmentally relevant concentrations ranging from 0.05X (29 µg REEs L -1 ) to 5X (2926 µg REEs L -1 ) to the test organism, Hydra vulgaris, at the morphological, reproductive and regenerative levels. The data showed that lethality occurred at concentrations near (2.5 fold) to those inducing sublethal effects after chronic exposure of 7 days. The mixture affected reproduction and head regeneration and even lethality at concentrations even below those reported at environmental concentration (0.5X = 293 µg REEs L -1 ) in lakes. This suggests that REEs concentrations found in lakes near mining activities could disrupt regeneration and impair embryonic development. Our data also revealed that combining the 5 REEs results in an antagonistic effect, suggesting that those elements share the same receptor and that low molecular weight and high radius elements (approaching iron) were less toxic. Taken together, hydra could be used as a sensitive model organism for the assessment of aquatic ecotoxicological risks of REE mixtures but further analyses of biochemical and gene expressions should improve our understanding of the long-term effects of REEs mixtures., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Rare earth elements (REEs) are contaminants of increasing interest due to intense mining activities for commercial purposes and ultimately released in the environment. We exposed juvenile rainbow trout (Oncorhynchus mykiss) to a representative mixture of the five most abundant REEs for 96 h at concentrations similar found in lakes contaminated by mining activities at 0.1, 1, 10, and 100X whereas the 1x mixture contained cerium (Ce, 280 μg/L), lanthanum (La, 140 μg/L), neodymium (Nd, 120 μg/L), praseodymium (Pr, 28 μg/L), and samarium (Sm, 23 μg/L). We investigated the expression of 14 genes involved in oxidative stress, DNA repair, tissue growth/proliferation, protein chaperoning, xenobiotic biotransformation, and ammonia metabolism in the liver. In addition, DNA damage, oxidative stress (lipid peroxidation or LPO), inflammation (cyclooxygenase or COX activity), detoxification mechanisms (glutathione-S-transferase activity or GST), and labile zinc were determined in gills. The data revealed that genes involved in oxidative stress-catalase (cat), heat shock proteins 70 (hsp70), and glutamate dehydrogenase (glud) were upregulated while glutathione S-transferase (gst) and metallothionein (mt) gene expressions were downregulated. The mixture was genotoxic and increased labile Zn in gills of exposed trout. These changes occurred at concentrations 600 times lower than the LC 50 for this mixture indicating effects below the 1X concentration. Based on principal component analysis and concentration-dependent reponses, the following sublethal effects were considered the most important/significant: DNA strand breaks (genotoxicity), labile Zn, cat, gst, hsp70, sparc, mt, and glud. These effects of fish juveniles are likely to occur in environments under the influence of mining activities.

Rare earth elements (REEs) have been recently identified as emergent contaminants because of their numerous and increasing applications in technology. The impact of REEs on downstream ecosystems, notably aquatic organisms, is of particular concern, but has to date been largely overlooked. The purpose of this study was thus to evaluate the toxicity of lanthanide metals, lutetium (Lu) and dysprosium (Dy) in rainbow trout after 96 h of exposure. The lethal concentration (LC50) was determined and the expression of 14 genes involved in different pathways such as oxidative stress, xenobiotic detoxification, mitochondrial respiration, DNA repair, protein folding and turnover, inflammation, calcium binding and ammonia metabolism were quantified in surviving fish. In parallel, lipid peroxidation (LPO), DNA damage (DSB), metallothionein level (MT) and cyclooxygenase activity (COX) were examined. The acute 96 h-LC 50 data revealed that Lu was more toxic than Dy (1.9 and 11.0 mg/L, respectively) and was able to affect all investigated pathways by changing the expression of the studied genes, to the exception of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). It also induced a decrease in DNA repair at concentrations 29 times below the LC 50 . This suggests that Lu could trigger a general stress to disrupt the cell homeostasis leading to genotoxicity without promoting oxidative stress. However, Dy induced modulation in the expression of genes involved in the protection against oxidative stress, detoxification, mitochondrial respiration, immunomodulation, protein turnover and an increase in the DNA strand breaks at concentrations 170 times lower than LC 50 . Changes in mRNA level transcripts could represent an early signal to prevent against toxicity of Dy, which exhibited inflammatory and genotoxic effects. This study thus provides useful knowledge enhancing our understanding of survival strategies developed by rainbow trout to cope with the presence of lanthanides in the environment., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Samarium (Sm) and yttrium (Y) are commonly used rare earth elements (REEs) but there is a scarcity of information concerning their biological effects in non-target aquatic organisms. The purpose of this study was to determine the bioavailability of those REEs and their toxicity on Dreissena polymorpha after exposure to increasing concentration of Sm and Y for 28 days at 15 °C. At the end of the exposure period, the gene expression of superoxide dismutase (SOD), catalase (CAT), metallothionein (MT), glutathione-S-transferase (GST), cytochrome c oxidase 1 (CO1) and cyclin D (Cyc D) were analysed. In addition, we examined lipid peroxidation (LPO), DNA strand breaks (DSB), GST and prostaglandin cyclooxygenase (COX) activities. Results showed a concentration dependent increase in the level of the REEs accumulated in the soft tissue of mussels. Both REEs decreased CAT but did not significantly modulated SOD and MT expressions. Furthermore, Sm 3+ up-regulated GST, CO1 and Cyc D, while Y 3+ increased and decreased GST and CO1 transcripts levels, respectively. Biomarker activities showed no oxidative damage as evidenced by LPO, while COX activity was decreased and DNA strand breaks levels were changed suggesting that Sm and Y exhibit anti-inflammatory and genotoxic effects. Factorial analysis revealed that the major impacted biomarkers by Sm were LPO, CAT, CO1 and COX, while GST gene expression, COX, Cyc D and CAT as the major biomarkers affected by Y. We conclude that these REEs display different mode of action but further investigations are required in order to define the exact mechanism involved in their toxicity., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Microplastics (MPs), plastic debris smaller than 5mm, are widely found in both marine and freshwater ecosystems. However, few studies regarding their hazardous effects on inland water organisms, have been conducted. For this reason, the aim of our research was the evaluation of uptake and chronic toxicity of two mixtures (MIXs) of virgin polystyrene microbeads (PMs) of 10μm and 1μm in size (MIX 1, with 5×10 5 of 1μmsizePMs/L and 5×10 5 of 10μmsizePMs/L, and MIX 2 with 2×10 6 of 1μmsizePMs/L and 2×10 6 of 10μmsizePMs/L) on freshwater zebra mussel Dreissena polymorpha (Mollusca: Bivalvia) during 6 exposure days. The PM uptake in the mussel body and hemolymph was assessed using confocal microscopy, while the chronic toxicity of PMs was evaluated on exposed mussels using a comprehensive battery of biomarkers of cellular stress, oxidative damage and neuro- genotoxicity. Confocal microscopy analyses showed that MPs concentrated in the gut lumen of exposed mussels, absorbed and transferred firstly in the tissues and then in the hemolymph. The results revealed that PMs do not produce oxidative stress and genetic damage, with the exception of a significant modulation of catalase and glutathione peroxidase activities in mussels exposed to MIX 1. Regarding neurotoxicity, we observed only a significant increase of dopamine concentration in mussels exposed to both MIXs, suggesting a possible implication of this neurotransmitter in an elimination process of accumulated PMs. This research represents a first study about the evaluation of virgin MP toxicity in zebra mussel and more research is warranted concerning the long term neurological effects of virgin MPs., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Gadolinium (Gd), a metal of the lanthanide series used in various industrial and medical purposes is released into the aquatic environment. However, there are few aquatic toxicological studies addressing environmental effects of Gd which remains unknown in aquatic animals. Therefore, this study aimed to compare the effects of GdCl 3 and a gadolinium-based MRI contrast agent (Omniscan), in zebra mussels after 28 days through a multibiomarker approach. Data revealed that after GdCl 3 exposure, the mRNA level of metallothionein (MT) was modulated, those of cytochrome c oxidase (CO1) and superoxide dismutase (SOD) were increased, while gene expressions of catalase (CAT) and glutathione-S-transferase (GST) were downregulated. Furthermore, neither lipoperoxidation (LPO) nor genotoxicity were detected but only a decrease in the cyclooxygenase (COX) activity was observed. In addition, a significant correlation was found between biomarkers and bioaccumulated Gd, suggesting that mitochondrial and anti-inflammatory pathways were triggered with GdCl 3 . By opposition, the contrasting agent formulation induced downregulation of SOD, CAT, GST and CO1, a decrease in the level of LPO and an increase in the GST and COX activities. This suggests that the chelated form of Gd did not promote reactive oxygen species (ROS) production and exhibits antioxidant and proinflammatory effects in mussels. Therefore, this study revealed that ionic and the chelated form of Gd influence different cellular pathways to initiate cellular changes., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Aromatic plants can interfere in the Mediterranean ecosystem, mainly by the introduction in the environment of volatile compounds. For this reason, we studied the chemical composition and the possible phytotoxic and antimicrobial activities of the essential oil extracted from leaves of Tunisian Artemisia herba-alba Asso. The chemical composition of the essential oil, obtained by hydrodistillation, was analyzed by GC and GC-MS. In all, 24 compounds were identified. The main components were camphor (39.1%), chrysanthenone (15.0%) and cis-thujone (7.8%). The essential oil was evaluated for its in vitro phytotoxic activity against germination and initial radical growth of Raphanus sativus L., Lepidium sativum L., Sinapis arvensis L., Triticum durum L. and Phalaris canariensis L. seeds. The radicle elongation of the five seeds was affected to different extents by the oil, while germination was not affected. The oil, when tested against eight selected bacterial strains, showed low antimicrobial activity. The chemical composition of the oil of A. herba-alba can help in the chemosystematics of this complex genus. However, the recorded biological activities seem to be neither ecologically nor medicinally significant.

Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often conflicting. The aim of the present study was to evaluate the effects of OA on heart clam cells and to analyse its possible mechanisms of action by investigating the signal transduction pathways involved in OA cytotoxicity. We showed that OA at 1 µM after 24 h of treatment induces disorganization of the actin cytoskeleton, rounding and detachment of fibroblastic cells. Moreover, treatment of heart cells revealed a sequential activation of MAPK proteins depending on the OA concentration. We suggest that the duration of p38 and JNK activation is a critical factor in determining cell apoptosis in clam cardiomyocytes. In the opposite, ERK activation could be involved in cell survival. The cell death induced by OA is a MAPK modulated pathway, mediated by caspase 3-dependent mechanism. OA was found to induce no significant effect on spontaneous beating rate or inward L-type calcium current in clam cardiomyocytes, suggesting that PP1 was not inhibited even by the highest dose of OA.

The chemical composition of the essential oils of Melaleuca armillaris Sm., Melaleuca styphelioides Sm. and Melaleuca acuminata F. Muell., collected in Tunisia, was studied by means of GC and GC-MS analysis. In all, 46 compounds were identified, 38 for M. armillaris, 20 for M. acuminata and eight for M. styphelioides, respectively. The presence of a sesquiterpenic fraction (52.2%) characterized the oil from M. armillaris; M. sthypheliodes oil was rich in methyl eugenol, a phenolic compound (91.1%), while M. acuminata oil is mainly constituted by oxygenated monoterpenoids (95.6%). The essential oils were evaluated for their in vitro potentially phytotoxic activity against germination and initial radicle growth of Raphanus sativus L., Lepidium sativum L., Sinapis arvensis L., Triticum durum L. and Phalaris canariensis L. seeds. The radicle elongation of five seeds was inhibited at the highest doses tested, while germination of all seeds was not affected. Moreover, the essential oils showed low antimicrobial activity against eight selected microorganisms.