Esofagitis disecante supeEsofagitis disecante superficial: dos casos de una misma entidad poco frecuente / Esophagitis dissecans superficialis: two cases of the same rare entity

La esofagitis disecante superficial (EDS) es una entidad infrecuente que se caracteriza endoscópicamente por el desprendimiento de las capas superficiales del epitelio esofágico e, histológicamente, por el aspecto bitonal del epitelio escamoso esofágico secundario a la necrosis de los estratos más superficiales. La etiología es desconocida, aunque se ha asociado con la ingesta de determinados fármacos, enfermedades autoinmunes, estasis esofágica y procedimientos endoscópicos. Presentamos dos casos: uno de ellos acontece en una mujer tras un episodio de disfagia abrupta y el segundo en un varón con comorbilidades y clínica de dolor epigástrico. La EDS es una patología que hay que considerar en su adecuado contexto clínico y endoscópico, ya que su curso es autolimitado en comparación con otras entidades de evolución tórpida o que precisan un tratamiento específico. (AU)

Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment. (AU)

[WHEN MEDICATIONS ARE NOT ENOUGH - NEUROFEEDBACK AS A COMPLEMENTARY TREATMENT FOR POST-TRAUMATIC STRESS DISORDER - A CASE REPORT].

INTRODUCTION: Neurofeedback (NF) therapy is brain training using operant conditioning including real-time displays of brain activity to teach people how to regulate their brain function. We would like to present a treatment for a patient who experienced severe traumatic events on 7/10 including physical injury accompanied by difficulty sleeping for two months, nightmares, intrusive thoughts, difficulties in emotional regulation and difficulty in concentrating. Due to the complexity and difficulties in emotional regulation accompanied by severe sleep disturbances, it was decided to treat with medication in combination with neurofeedback. After several training sessions in addition to pharmaceutical treatment, significant relaxation was observed, there was an improvement in concentration and the patient was able to return to his work and normal social functioning. In addition, intrusive thoughts decreased in intensity and frequency.

Olive Pomace Extract Contains Low Molecular Weight Peptides and Possesses ACE Inhibitory Activity.

The aim of the present study was to determine the ACE inhibitory activity of aqueous extracts of olive pomace and to understand whether they represent a good source of bioactive LMW peptides for nutritional and pharmacological applications. We produced a water extract from olive pomace (var. Picual) and obtained its low molecular weight (LMW) fraction (<3 kDa). The calculated yield of extraction was 100.2 ± 7.9 mg of LMW peptides per 100 g of olive pomace. The olive pomace LMW fraction possessed strong ACE inhibitory activity (IC50 = 3.57 ± 0.22 µg prot/mL). The LMW fraction (<3 kDa) was analysed by nanoscale liquid chromatography-Orbitrap coupled with tandem mass spectrometry and de novo sequencing. Thirty new peptides, containing between 7-17 amino acids and molecular masses ranging 778-1354 Da, were identified by the Peaks database algorithm using the available Olea europaea (cv. Farga) genome database. Ten new peptides were also identified by Peaks de novo sequencing. The protein sources of twelve peptides detected in the database by Peaks DB were identified by BLAST search. The ACE inhibitory activity of the identified peptides was predicted by BIOPEP software. We conclude that olive pomace possesses ACE inhibitory activity and contains low molecular weight peptides with (predicted) biological activity. Olive pomace may represent a good source of peptides for nutritional and pharmaceutical applications. In our study, it has been shown that olive pomace possesses ACE inhibitory activity and contains low molecular weight peptides with (predicted) biological activity. Olive pomace may represent a good source of peptides for nutritional and pharmaceutical applications. More research is needed in order to identify the in vivo effects of olive pomace bioactive peptides.

Unified Methodology for the Primary Preclinical In Vivo Screening of New Anticoagulant Pharmaceutical Agents from Hematophagous Organisms.

The development of novel anticoagulants requires a comprehensive investigational approach that is capable of characterizing different aspects of antithrombotic activity. The necessary experiments include both in vitro assays and studies on animal models. The required in vivo approaches include the assessment of pharmacokinetic and pharmacodynamic profiles and studies of hemorrhagic and antithrombotic effects. Comparison of anticoagulants with different mechanisms of action and administration types requires unification of the experiment scheme and its adaptation to existing laboratory conditions. The rodent thrombosis models in combination with the assessment of hemostasis parameters and hematological analysis are the classic methods for conducting preclinical studies. We report an approach for the comparative study of the activity of different anticoagulants in vivo, including the investigation of pharmacodynamics and the assessment of hemorrhagic effects (tail-cut bleeding model) and pathological thrombus formation (inferior vena cava stenosis model of venous thrombosis). The reproducibility and uniformity of our set of experiments were illustrated on unfractionated heparin and dabigatran etexilate (the most common pharmaceuticals in antithrombic therapy) as comparator drugs and an experimental drug variegin from the tick Amblyomma variegatum. Variegin is notorious since it is a potential analogue of bivalirudin (Angiomax, Novartis AG, Basel, Switzerland), which is now being actively introduced into antithrombotic therapy.

Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.

The endoplasmic reticulum maintains proteostasis, which can be disrupted by oxidative stress, nutrient deprivation, hypoxia, lack of ATP, and toxicity caused by xenobiotic compounds, all of which can result in the accumulation of misfolded proteins. These stressors activate the unfolded protein response (UPR), which aims to restore proteostasis and avoid cell death. However, endoplasmic response-associated degradation (ERAD) is sometimes triggered to degrade the misfolded and unassembled proteins instead. If stress persists, cells activate three sensors: PERK, IRE-1, and ATF6. Glioma cells can use these sensors to remain unresponsive to chemotherapeutic treatments. In such cases, the activation of ATF4 via PERK and some proteins via IRE-1 can promote several types of cell death. The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.

Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: Opportunities, challenges, and insights into liquid chromatography-mass spectrometry strategies.

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.

Evaluation of the DGT passive samplers for integrating fluctuating concentrations of pharmaceuticals in surface water.

Diffusive gradients in thin films (DGTs) have been well-documented for the measurement of a broad range of organic pollutants in surface water. However, the performance has been challenged by the inherent periodic concentration fluctuations for most organic pollutants. Therefore, there is an urgent need to assess the true time-weighted average (TWA) concentration based on fluctuating concentration profiles. The study aimed to evaluate the responsiveness of DGT and accuracy of TWA concentrations, considering various concentration fluctuating scenarios of 20 pharmaceuticals in surface water. The reliability and accuracy of the TWA concentrations measured by the DGT were assessed by comparison with the sum of cumulative mass of DGT exposed at different stages over the deployment period. The results showed that peak concentration duration (1-5 days), peak concentration fluctuation intensity (6-20 times), and occurrence time of peak concentration fluctuation (early, middle, and late stages) have minimal effect on DGT's response to most target pharmaceutical concentration fluctuations (0.8 < CDGT/CTWA < 1.2). While the downward-bent accumulations of a few pharmaceuticals on DGT occur as the sampling time increases, which could be accounted for by capacity effects during a long-time sampling period. Additionally, the DGT device had good sampling performance in recording short fluctuating concentrations from a pulse event returning to background concentrations with variable intensity and duration. This study revealed a satisfactory capacity for the evaluation of the TWA concentration of pharmaceuticals integrated over the period of different pulse deployment for DGT, suggesting that this passive sampler is ideally suited as a monitoring tool for field application. This study represents the first trial for evaluating DGT sampling performance for pharmaceuticals with multiple concentration fluctuating scenarios over time, which would be valuable for assessing the pollution status in future monitoring campaign.

Temperature-dependent toxicity of fluoxetine alters the thermal plasticity of marine diatoms.

Anthropogenic activities have led to the emergence of pharmaceutical pollution in marine ecosystems, posing a significant threat to biodiversity in conjunction with global climate change. While the ecotoxicity of human drugs on aquatic organisms is increasingly recognized, their interactions with environmental factors, such as temperature, remain understudied. This research investigates the physiological effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on two diatom species, Phaeodactylum tricornutum and Thalassiosira weissflogii. Results demonstrate that fluoxetine significantly reduces growth rate and biomass production, concurrently affecting pigment contents and the thermal performance curve (TPC) of the diatoms. Fluoxetine reduces the synthesis of chlorophyll a (Chl a) and carotenoid (Car), indicating inhibition of photosynthesis and photoprotection. Furthermore, fluoxetine decreases the maximum growth rate (µmax) while increasing the optimum temperature (Topt) in both species, suggesting an altered thermal plasticity. This shift is attributed to the observed decrease in the inhibition rate of fluoxetine with rising temperatures. These findings emphasize the physiological impacts and ecological implications of fluoxetine on phytoplankton and underscore the significance of considering interactions between multiple environmental drivers when accessing the ecotoxicity of potential pollutants. The present study provides insights into crucial considerations for evaluating the impacts of pharmaceutical pollution on marine primary producers.

Conflicts of Interest Among Cardiology Clinical Practice Guideline Authors in Japan.

BACKGROUND: Clinical practice guidelines (CPGs) offer disease management recommendations based on scientific evidence. However, financial conflicts of interest between CPG developers and the pharmaceutical industry could bias these recommendations, potentially affecting patient care. Proper management of these conflicts of interest is particularly crucial for maintaining the integrity of CPGs. The study aimed to evaluate the extent of financial relationships between the pharmaceutical industry and authors of CPGs for cardiovascular diseases in Japan. METHODS AND RESULTS: The study analyzed personal payments from the pharmaceutical industry to authors of cardiovascular disease CPGs published by the Japanese Circulation Society from January 2015 to December 2022. Payment data, including speaking, consultancy, and writing fees from 2016 to 2020, were extracted from a publicly available database containing personal payments disclosed by all major pharmaceutical companies. A total of 929 unique authors from 37 eligible Japanese Circulation Society CPGs were identified. Notably, 94.4% of these authors received personal payments from pharmaceutical companies, totaling >US $70.8 million. The mean±SD payment per author was US $76 314±138 663) and the median payment per author was US $20 792 (interquartile range: US $4262-US $76 998) over the 5-year period. Chairs of CPGs received significantly higher payments than other authors. More than 80% of authors in each CPG received personal payments. CONCLUSIONS: The study elucidated that there were considerable financial relationships between pharmaceutical companies and cardiology CPG authors in Japan. This finding deviates from international conflict of interest management policies, suggesting the need for more stringent conflict of interest management strategies by the Japanese Circulation Society to ensure the development of trustworthy and evidence-based CPGs.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

Parental exposure to antidepressants has lasting effects on offspring? A case study with zebrafish.

Fish have common neurotransmitter pathways with humans, exhibiting a significant degree of conservation and homology. Thus, exposure to fluoxetine makes fish potentially susceptible to biochemical and physiological changes, similarly to what is observed in humans. Over the years, several studies demonstrated the potential effects of fluoxetine on different fish species and at different levels of biological organization. However, the effects of parental exposure to unexposed offspring remain largely unknown. The consequences of 15-day parental exposure to relevant concentrations of fluoxetine (100 and 1000 ng/L) were assessed on offspring using zebrafish as a model organism. Parental exposure resulted in offspring early hatching, non-inflation of the swimming bladder, increased malformation frequency, decreased heart rate and blood flow, and reduced growth. Additionally, a significant behavioral impairment was also found (reduced startle response, basal locomotor activity, and altered non-associative learning during early stages and a negative geotaxis and scototaxis, reduced thigmotaxis, and anti-social behavior at later life stages). These behavior alterations are consistent with decreased anxiety, a significant increase in the expression of the monoaminergic genes slc6a4a (sert), slc6a3 (dat), slc18a2 (vmat2), mao, tph1a, and th2, and altered levels of monoaminergic neurotransmitters. Alterations in behavior, expression of monoaminergic genes, and neurotransmitter levels persisted until offspring adulthood. Given the high conservation of neuronal pathways between fish and humans, data show the possibility of potential transgenerational and multigenerational effects of pharmaceuticals' exposure. These results reinforce the need for transgenerational and multigenerational studies in fish, under realistic scenarios, to provide realistic insights into the impact of these pharmaceuticals.

Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery.

Microneedle (MN)-assisted drug delivery technology has gained increasing attention over the past two decades. Its advantages of self-management and being minimally invasive could allow this technology to be an alternative to hypodermic needles. MNs can penetrate the stratum corneum and deliver active ingredients to the body through the dermal tissue in a controlled and sustained release. Long-acting polymeric MNs can reduce administration frequency to improve patient compliance and therapeutic outcomes, especially in the management of chronic diseases. In addition, long-acting MNs could avoid gastrointestinal reactions and reduce side effects, which has potential value for clinical application. In this paper, advances in design strategies and applications of long-acting polymeric MNs are reviewed. We also discuss the challenges in scale manufacture and regulations of polymeric MN systems. These two aspects will accelerate the effective clinical translation of MN products.

Home symptom management training programme: carer evaluation.

OBJECTIVES: Most people say if they had a terminal illness, they would prefer to be cared for at home and, if possible, to die there. Often this is not possible without a carer to assist with on-going practical care and symptom management. If breakthrough symptoms are not treated in a timely manner, symptoms can escalate quickly causing increased suffering resulting in unwanted hospital transfers. Many carers report feeling motivated but uneducated for the task of medicine management, especially if it involves preparation and/or administration of subcutaneous medicines This study assesses the impact of an education and resource package, caring@home, on carers' confidence, knowledge, and skills in managing palliative symptoms at home using subcutaneous medicines. METHODS: Nurses trained volunteer carers on the use of the package. Carers were invited to complete a 10 min written evaluation survey and to consider consenting to a 30 min semistructure phone interview. RESULTS: Fifty carers returned surveys and 12 were interviewed. Most carers agreed or strongly agreed that the package provided them with the necessary knowledge, skills and confidence to safely and confidently manage breakthrough symptoms using subcutaneous medicines, further, they would recommend the package to others. Interview analysis revealed three main themes: (1) hesitation and motivation to adopt expanded carer role; (2) the importance of a layered approach to support; and (3) avoiding perceived unnecessary contact with nurses. CONCLUSION: The programme can be used by clinical services to empower carers to help enable a person to be cared for, and to die at home.

Nose-to-brain delivery of nanotherapeutics: Transport mechanisms and applications.

The blood-brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption-mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose-to-brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Patient versus physician preferences for lipid-lowering drug therapy: A discrete choice experiment.

BACKGROUND: The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors offered dyslipidemia patients an alternative to statins for lipid-lowering treatment. Understanding patient and physician preferences for lipid-lowering drugs may promote shared decision-making and improve treatment outcomes. METHODS: This study utilized an online discrete choice experiment (DCE) to assess the relative importance (RI) of six attributes related to lipid-lowering drugs, including frequency of administration, mode of administration, reduction of low-density lipoprotein cholesterol (LDL-C) level, risk of myopathy, risk of liver damage, and out-of-pocket monthly cost. Respondents were recruited from dyslipidemia patients and cardiovascular physicians in China. A mixed logit model and latent class analysis were employed to estimate the preference coefficient, marginal willingness to pay (mWTP), and RI of attributes. Ethical approval has been obtained for this study. RESULTS: A total of 708 patients and 507 physicians participated in the survey. Patients prioritized the 'risk of liver damage' (RI = 23.6%) with 'mode of administration' (RI = 19.2%) and 'frequency of administration' (RI = 18.8%) following closely. Contrarily, physicians prioritized the 'reduction of LDL-C level' (RI = 33.5%), followed by 'risk of liver damage' (RI = 26.0%) and 'risk of myopathy' (RI = 16.1%). Patients placed a higher value on 'frequency of administration' (p < .001) and 'mode of administration' (p < .001) compared to physicians, while physicians valued 'reduction of LDL-C level' (p < .001) and 'risk of myopathy' (p = .012) more than patients. Physicians exhibited higher mWTP than patients for all attributes except frequency and mode of administration. The LCA revealed three distinct patient classes: focus on oral administration, focus on hepatic safety and frequency and focus on hepatic safety and cost. Likewise, three physician classes were identified: frequency-insensitive, efficacy-focused and safety-focused. CONCLUSIONS: The preferences for lipid-lowering drug therapy differed between patients and physicians in China. Physicians should take into account patients' preferences and provide personalized treatment when they formulate lipid-lowering treatment plans. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in the questionnaire design process. They engaged in a focus group discussion to determine attributes and levels and also participated in a pilot survey to assess the comprehensibility of the questionnaires. Additionally, patients were involved in the DCE survey to express their preferences. The findings of patient preference for lipid-lowering drug therapy will promote shared decision-making and optimize the treatment regimen.

Paving the Path for Sustainable and Responsible Off-Label Use of Pharmaceutical Products in Europe.

Off-label use of pharmaceuticals involves a wide array of aspects ranging from legal and regulatory ones to clinical to safety considerations. Access to off-label therapies is particularly relevant question for patients in areas of unmet medical need. Simultaneously, off-label use also triggers wider considerations relating to social and economic sustainability of health care systems and access to health. National authorities have adapted different regulatory approaches to off-label use of pharmaceuticals, ranging from (1) "regulatory silence"; to (2) allowing off-label use at the discretion of the treating physician; and to (3) a more stringent approach in which off-label use is subject to third party approval. This article provides a brief overview of these different regulatory approaches from a helicopter perspective, and it discusses benefits and shortcomings these approaches. Finally, it presents ideas for preconditions for sustainable and responsible off-label use of pharmaceutical products to ensure patient safety whilst ensuring their timely access to health.

How does the problem-oriented innovation system (PIS) help in the management of cardiovascular diseases?

Introduction: Cardiovascular diseases are a multifaceted and complex problem in the health system that can change the priorities of the economic, social, and even political systems of countries. Therefore, as a grand challenge (GC), its management requires adopting a systematic, interdisciplinary, and innovative approach. In Iran, the most common causes of death, have changed from infectious and diarrheal diseases to cardiovascular diseases since 1960. Methods: In this study, the novel framework of the problem-oriented innovation system (PIS) has been used, and cardiovascular diseases in Iran have been selected as a case study. To this end, first, the main challenges related to cardiovascular diseases in Iran were identified in two layers of "governance-centered" (including legal and policy gaps, insufficient education, financing, lack and unbalanced distribution of medical personnel) and "society driven" (including unhealthy diet and lifestyle, uncontrolled and hard-to-regulate factors, and high costs) through a library research. Then, the functional-structural framework of the problem-oriented innovation system was used to analyze cardiovascular diseases and provide policy recommendations. Results: The findings indicate that based on the eight functions of the problem-oriented innovation system, an important part of cardiovascular diseases can be managed and controlled in three short-term, medium-term, and long-term periods. Conclusion: Increasing public awareness in the form of university courses, participation of the government with the private sector in building and equipping specialized cardiovascular centers, creating an electronic health record from birth, implementing a family health plan focusing on less developed areas, supporting agriculture and guaranteeing the purchase of agricultural products and healthy food, increasing the capacity of accepting students in medical and paramedical fields, and allocating pharmaceutical currency in the form of pharmaceutical subsidies directly to cardiovascular patients, are among the most important policy recommendations for this grand challenge.

Financial Relationships Between Pharmaceutical Companies and Internal Medicine Societies.

This cross-sectional study uses payment data publicly disclosed by pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association to describe their financial relationships with the subspecialty societies of the Japanese Society of Internal Medicine.

Seasonal patterns, fate and ecological risk assessment of pharmaceutical compounds in a wastewater treatment plant with Bacillus bio-reactor treatment.

Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.

Lusutrombopag as a Repurposing Drug in Combination with Aminoglycosides against Vancomycin-Resistant Enterococcus.

Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus in vitro with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects in vitro and in vivo against Enterococcus. No in vitro or in vivo detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.