In the context of the shift toward a closed-loop economy, soil-like fractions from landfills are increasingly seen as a potential raw material. Pollution, including potentially toxic elements (PTEs), limits the use of soil-like fractions. The study objective was to assess the level of contamination with PTEs and the ecological risk of the soil-like fraction from a landfill using an interval method on the basis of a quantile analysis. Quantile analysis allows visualization and interpretation of data based on statistical principles using a cumulative distribution function for the data. Quantiles divide the entire dataset into equal parts by probability, and they indicate the proportion of observations that have a value less than or equal to a given quantile. A study was conducted at a landfill in Volgograd. The contents of Cd, Ni, Pb, Hg, Cu, and Zn were studied in a soil-like fraction. The contents of Hg, Pb, and Zn were low and did not pose any risks to the environment. Cd, Ni, and Cu were the main reasons for the contamination of the soil-like fraction. Quantile analysis has shown that the soil-like fraction is polluted unevenly and is described by several contamination levels. The pollution level with PTEs in the soil-like fraction is low, with a probability of 27-31%. The other part of the soil-like fraction has a pollution level ranging from moderate to very high. The environmental risk of a soil-like fraction is associated with Cd and Ni. With a probability of 23.5%, a soil-like fraction is a high environmental risk and requires a responsible attitude and measures to ensure environmental safety. With probabilities of 29.4% and 47.1%, the complex potential environmental risks of a soil-like fraction are low and moderate, respectively. The soil-like fraction located at a depth of more than 2.5 m has a low level of pollution and a low environmental risk. Potentially, this part of a soil-like fraction can be isolated and, after detoxification, used. The significance of this research lies in providing a novel approach to evaluate the ecological risk of soil-like fractions from landfills, which can inform more effective sustainable waste utilization practices in landfill mining.

UNASSIGNED: Postoperative venous thromboembolism (VTE) risk is pronounced after abdominal cancer surgery. Enoxaparin shows promise in preventing VTE in gastrointestinal, gynecological, and urological cancers, but its application after surgery for hepatobiliary-pancreatic malignancy has been under-evaluated due to bleeding concerns. We confirmed the safety of enoxaparin administration in patients undergoing curative hepatobiliary-pancreatic surgery for malignancies in a prospective, multi-center, phase I study.
UNASSIGNED: The study was conducted from April 2015 to May 2021 across eight specialized centers. Patients (n = 262) were randomized to enoxaparin prophylaxis given postoperatively for 8 days (n = 131) or control (n = 131). The primary endpoint was the efficacy in reducing VTE. Secondary endpoints examined safety.
UNASSIGNED: The full analysis set included 259 patients (131 control, 129 enoxaparin). The per-protocol population included 233 patients (117 control, 116 enoxaparin). Most cases were hepatic malignancies (111 control, 111 enoxaparin). The median administration duration of enoxaparin was 7 days, with 92% receiving 4000 units/day. Despite a reduction in the relative risk (RR) of VTE due to postoperative enoxaparin administration, the results were not significant (control: four cases, 3.4% vs. treatment: two cases, 1.7%; RR 0.50, 95% CI 0.09-2.70; p = 0.6834). No significant difference was found in the incidence of bleeding events (control: five cases, 4.3% vs. treatment: five cases, 4.3%, RR 1.00, 95% CI 0.53-1.89; p = 1.0000).
UNASSIGNED: The perioperative administration of enoxaparin in hepatobiliary-pancreatic malignancies is feasible and safe. However, further case accumulation and investigation are necessary to assess its potential in reducing the occurrence of VTE.

Industrial activities on the banks of waterways can degrade both the waterbody and the surrounding area and continue to exert pressure on the environment even after the closure of the industries involved. An assessment was undertaken to determine concentration, distribution, mobility and ecological risk of potentially toxic elements (PTE) from legacy contamination in sediments of the Forth and Clyde Canal, UK. Concentrations of PTE, determined by ICP-MS following aqua regia digestion, were 5.54-219 mg kg-1 for As, < 0.025-11.0 mg kg-1 for Cd, 44.8-883 mg kg-1 for Cr, 39.3-618 mg kg-1 for Cu, 35.8-72.1 g kg-1 for Fe, 720-4460 mg kg-1 for Mn, 42.0-154 mg kg-1 for Ni, 93.9-2740 mg kg-1 for Pb, 5.36-122 mg kg-1 for Sn and 288-3640 mg kg-1 for Zn. With the exception of Fe and Mn, higher levels were observed at urban locations than at rural. Enhanced Cr, Pb and Sn content at suburban locations could be attributed to historical industrial activities on the canal bank, while widespread distribution of As and Pb was consistent with atmospheric deposition. In the inner-city area, sediment quality was severely deteriorated, and the potential ecological risk was very high. Fractionation patterns, determined using the modified BCR sequential extraction, indicated a particularly high risk of mobilization for Cd, Mn and Zn, and the highest exchangeable fraction risk from Zn. The research highlights the need to assess and, where necessary, manage legacy contaminated sites in line with the UN 2030 Agenda for Sustainable Development.

Specific stereoisomer is paramount as it is vital for optimizing drug efficacy and safety. The quest for the isolation of desired stereoisomer of active pharmaceutical ingredients or key intermediates drives innovation in drug synthetic and biocatalytic methods. Chiral phosphoramidate is an important building block for the synthesis of antiviral drugs such as remdesivir and sofosbuvir. Given the clinical potency of the (Sp)-diastereomer of the drugs, an enzyme capable of completely hydrolyzing the (Rp)-diastereomer is needed to achieve the purified diastereomers via biocatalytic reaction. In this study, protein engineering of phosphotriesterase (PTE) was aimed to improve the specificity. Employing rational design and site-directed mutagenesis, we generated a small library comprising 24 variants for activity screening. Notably, W131M and I106A/W131M variants demonstrated successful preparation of pure (Sp)-diastereomer of remdesivir and sofosbuvir precursors within a remarkably short hydrolysis time (<20 min). Our work unveils a promising methodology for producing pure stereoisomeric compounds, utilizing novel biocatalysts to enable the chemoenzymatic synthesis of phosphoramidate nucleoside prodrugs.

Antiphospholipid syndrome is an immunopathologic disorder that should be considered in all patients with recurrent and/or unexplained thromboembolic events. Antiphospholipid antibodies are diagnostic markers, and anticoagulation therapy is the therapeutic and preventive strategy. Long-term anticoagulation therapy is necessary, with careful attention to potential bleeding complications.

Pulmonary embolism (PE) is a life-threatening condition resulting from the obstruction of pulmonary arteries by blood clots, usually originating from deep veins. Symptoms of PE might vary from nothing to sudden death. Clinically, individuals may present very differently. When a diagnosis of PE is suspected, any possible life-saving intervention must be implemented because survival from cardiac arrest following PE is often quite low. Although there are not many randomized controlled trials that provide guidelines for treating suspected PE in cardiac arrest victims, the few published case reports and other minor studies suggest that thrombolysis and other therapies are associated with good outcomes. We report a patient with PE who presented in cardiac arrest with its clinical, electrographic, and radiologic findings, along with the appropriate therapy chosen based on hemodynamic stability. It is important to intervene early to prevent severe complications and improve the patient\'s outcomes.

UNASSIGNED: Medical devices can seek patent term extensions (PTEs), which extend market exclusivity to compensate for delays related to clinical trials and regulatory review. Pharmaceutical companies commonly use PTEs, but their use by medical device companies has not been clear.
UNASSIGNED: We examined the use of PTEs by medical device companies between 1984 and 2024 using a database published in the Federal Register and a list published by the Patent and Trademark Office.
UNASSIGNED: Only 178 medical device submissions were linked to a PTE application. They were mostly concentrated in 116 product codes associated with 15 medical specialties; nearly half were associated with cardiovascular devices. Numbers increased significantly in the past decade. Successful applications restored 987 days on average.
UNASSIGNED: The patent restoration opportunity appears underutilized. It is unclear whether some companies do not recognize the opportunity it promises, or whether it does not meet their needs. Different business features and marketing strategies in device versus pharmaceutical industries may decrease the usefulness of the PTE program for these types of medical products. However, the finding that a small subset of manufacturers operating in competitive markets adopted patent extension strategies more commonly suggests a significant competitive advantage when competition increases.

OBJECTIVE: This study was undertaken to examine how pediatric traumatic brain injury (pTBI) correlates with incidence of epilepsy at later ages in Finland.
METHODS: This nationwide retrospective register-based cohort study extended from 1998 to 2018. The study group consisted of 71 969 pediatric (<18 years old) patients hospitalized with TBI and a control group consisting of 64 856 pediatric patients with distal extremity fracture. Epilepsy diagnoses were gathered from the Finnish Social Insurance Institution. Kaplan-Meier and multivariable Cox regression models were conducted to analyze the probability of epilepsy with 95% confidence intervals (CIs).
RESULTS: Cumulative incidence rates (CIRs) for the first 2 years were .5% in the pTBI group and .1% in the control group. The corresponding rates after 15 years of follow-up were 1.5% in the pTBI group and .7% in the control group. Due to proportional hazard violations, the study population was split to the first 2 years and in subgroup analysis 4 years. During the first 2 years of surveillance, the hazard ratio (HR) for the pTBI group was 4.38 (95% CI = 3.39-5.66). However, between years 2 and 20, the HR for the pTBI group was 2.02 (95% CI = 1.71-2.38). A total of 337 patients (.47%) underwent neurosurgery, and 36 (10.7%) patients subsequently developed epilepsy. The CIR for the first year after TBI was 4.5% (95% CI = 2.3-6.7) in operatively managed patients and .3% (95% CI = .3-.4) in nonoperatively managed patients. Corresponding figures after 15 years were 12.0% (95% CI = 8.2-15.8) and 1.5% (95% CI = 1.4-1.6). During the first 4 years of surveillance, the HR for the operative pTBI group was 14.37 (95% CI = 9.29-20.80) and 3.67 (95% CI = 1.63-8.22) between years 4 and 20.
CONCLUSIONS: pTBI exposes patients to a higher risk for posttraumatic epilepsy for many years after initial trauma. Children who undergo operative management for TBI have a high risk for epilepsy, and this risk was highest during the first 4 years after injury.

Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is the kidney, where it accumulates. In the present narrative review, we assessed experimental and clinical data dealing with the mechanisms of kidney morphological and functional damage caused by Cd and the state of the art about possible therapeutic managements. Intriguingly, skeleton fragility related to Cd exposure has been demonstrated to be induced both by a direct Cd toxic effect on bone mineralization and by renal failure. Our team and other research groups studied the possible pathophysiological molecular pathways induced by Cd, such as lipid peroxidation, inflammation, programmed cell death, and hormonal kidney discrepancy, that, through further molecular crosstalk, trigger serious glomerular and tubular injury, leading to chronic kidney disease (CKD). Moreover, CKD is associated with the presence of dysbiosis, and the results of recent studies have confirmed the altered composition and functions of the gut microbial communities in CKD. Therefore, as recent knowledge demonstrates a strong connection between diet, food components, and CKD management, and also taking into account that gut microbiota are very sensitive to these biological factors and environmental pollutants, nutraceuticals, mainly present in foods typical of the Mediterranean diet, can be considered a safe therapeutic strategy in Cd-induced kidney damage and, accordingly, could help in the prevention and treatment of CKD.

Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under investigation. The dentate gyrus-a structure that is highly susceptible to injury-has been implicated in the evolution of seizure development.
Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by unbiased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching, and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-Seq were performed to determine differential gene expression in animals that developed post-traumatic epilepsy (PTE+) vs. those animals that did not (PTE-), which may be associated with epileptogenesis.
CCI injury resulted in 37% PTE incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions, which showed increased astroglial expression in the PTE+ hilus.
These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.