Free water surface constructed wetlands: review of pollutant removal performance and modeling approaches.

Free water surface constructed wetlands (FWSCWs) for the treatment of various wastewater types have evolved significantly over the last few decades. With an increasing need and interest in FWSCWs applications worldwide due to their cost-effectiveness and other benefits, this paper reviews recent literature on FWSCWs' ability to remove different types of pollutants such as nutrients (i.e., TN, TP, NH4-N), heavy metals (i.e., Fe, Zn, and Ni), antibiotics (i.e., oxytetracycline, ciprofloxacin, doxycycline, sulfamethazine, and ofloxacin), and pesticides (i.e., Atrazine, S-Metolachlor, imidacloprid, lambda-cyhalothrin, diuron 3,4-dichloroanilin, Simazine, and Atrazine) that may co-exist in wetland inflow, and discusses approaches for simulating hydraulic and pollutant removal processes. A bibliometric analysis of recent literature reveals that China has the highest number of publications, followed by the USA. The collected data show that FWSCWs can remove an average of 61.6%, 67.8%, 54.7%, and 72.85% of inflowing nutrients, heavy metals, antibiotics, and pesticides, respectively. Optimizing each pollutant removal process requires specific design parameters. Removing heavy metal requires the lowest hydraulic retention time (HRT) (average of 4.78 days), removing pesticides requires the lowest water depth (average of 0.34 m), and nutrient removal requires the largest system size. Vegetation, especially Typha spp. and Phragmites spp., play an important role in FWSCWs' system performance, making significant contributions to the removal process. Various modeling approaches (i.e., black-box and process-based) were comprehensively reviewed, revealing the need for including the internal process mechanisms related to the biological processes along with plants spp., that supported by a further research with field study validations. This work presents a state-of-the-art, systematic, and comparative discussion on the efficiency of FWSCWs in removing different pollutants, main design factors, the vegetation, and well-described models for performance prediction.

Shotgun metagenomic insights into secondary metabolite biosynthetic gene clusters reveal taxonomic and functional profiles of microbiomes in natural farmland soil.

Antibiotic resistance is a worldwide problem that imposes a devastating effect on developing countries and requires immediate interventions. Initially, most of the antibiotic drugs were identified by culturing soil microbes. However, this method is prone to discovering the same antibiotics repeatedly. The present study employed a shotgun metagenomics approach to investigate the taxonomic diversity, functional potential, and biosynthetic capacity of microbiomes from two natural agricultural farmlands located in Bekeka and Welmera Choke Kebelle in Ethiopia for the first time. Analysis of the small subunit rRNA revealed bacterial domain accounting for 83.33% and 87.24% in the two selected natural farmlands. Additionally, the analysis showed the dominance of Proteobacteria representing 27.27% and 28.79% followed by Actinobacteria making up 12.73% and 13.64% of the phyla composition. Furthermore, the analysis revealed the presence of unassigned bacteria in the studied samples. The metagenome functional analysis showed 176,961 and 104, 636 number of protein-coding sequences (pCDS) from the two samples found a match with 172,655 and 102, 275 numbers of InterPro entries, respectively. The Genome ontology annotation suggests the presence of 5517 and 3293 pCDS assigned to the "biosynthesis process". Numerous Kyoto Encyclopedia of Genes and Genomes modules (KEGG modules) involved in the biosynthesis of terpenoids and polyketides were identified. Furthermore, both known and novel Biosynthetic gene clusters, responsible for the production of secondary metabolites, such as polyketide synthases, non-ribosomal peptide synthetase, ribosomally synthesized and post-translationally modified peptides (Ripp), and Terpene, were discovered. Generally, from the results it can be concluded that the microbiomes in the selected sampling sites have a hidden functional potential for the biosynthesis of secondary metabolites. Overall, this study can serve as a strong preliminary step in the long journey of bringing new antibiotics to the market.

Improved Diagnosis and Treatment Monitoring of Tuberculosis Using Stool and the Tuberculosis Bacterial Load Assay (TB-MBLA).

The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment. We have shown that stool is a potential alternative sample type for diagnosis of tuberculosis. Currently, available protocols like the Xpert MTB/RIF use DNA as a target to detect Mycobacterium tuberculosis in stool but DNA survives long after the organism is dead so it is not certain whether a positive test is from an old or a partially treated infection. The TB MBLA only detects live organisms and thus, can be used to follow the response to treatment. In this chapter, we describe a protocol for TB-MBLA, an RNA-based assay, and apply it to quantify TB bacteria in stool.

Applying Machine Learning for Antibiotic Development and Prediction of Microbial Resistance.

Antimicrobial resistance (AMR) poses a serious threat to human health worldwide. It is now more challenging than ever to introduce a potent antibiotic to the market considering rapid emergence of antimicrobial resistance, surpassing the rate of antibiotic drug discovery. Hence, new approaches need to be developed to accelerate the rate of drug discovery process and meet the demands for new antibiotics, while reducing the cost of their development. Machine learning holds immense promise of becoming a useful tool, especially since in the last two decades, exponential growth has occurred in computational power and biological big data analytics. Recent advancements in machine learning algorithms for drug discovery have provided significant clues for potential antibiotic classes. Apart from discovery of new scaffolds, machine learning protocols will significantly impact prediction of AMR patterns and drug metabolism. In this review, we outline power of machine learning in antibiotic drug discovery, metabolic fate, and AMR prediction to support researchers engaged and interested in this field.

Using the Zebrafish Larval Model of Infection to Investigate Antibiotic Efficacy and Combination Treatments Against Staphylococcus aureus.

There is an increasing need for new treatment regimens to combat antibiotic-resistant strains of bacteria. Staphylococcus aureus is a clinically important, opportunist pathogen that has developed resistance to a range of antibiotics. The zebrafish larval model of systemic disease has been increasingly utilized to elucidate S. aureus virulence mechanisms and host-pathogen interactions. Here, we outline how this model can be used to investigate the effects of different antibiotics alone and in combination against S. aureus.

Antimicrobial resistance is not increasing in subsequent cases of ischaemic foot infections, a single-centre cohort from 2012 to 2021.

Patients with chronic limb-threatening ischaemia (CLTI) are at risk of foot infections, which is associated with an increase in amputation rates. The use of antibiotics may lead to a higher incidence of antimicrobial resistance (AMR) in subsequent episodes of ischaemic foot infections (IFI). This retrospective single-centre cohort study included 130 patients with IFI undergoing endovascular revascularisation. Staphylococcus aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 20.5% and 10.8% of cases, respectively. The prevalence of antimicrobial resistance (AMR) and multi-drug resistance did not significantly increase between episodes (10.2% vs. 13.4%, p = 0.42). In 59% of subsequent episodes, the identified pathogens were unrelated to the previous episode. However, the partial concordance of identified pathogens significantly increased to 66.7% when S. aureus was identified (p = 0.027). Subsequent episodes of IFI in the same patient are likely to differ in causative pathogens. However, in the case of S. aureus, the risk of reinfection, particularly with S. aureus, is increased. Multi-drug resistance does not appear to change between IFI episodes. Therefore, recommendations for empirical antimicrobial therapy should be based on local pathogen and resistance statistics without the need to broaden the spectrum of antibiotics in subsequent episodes.

Biocompatibility Evaluation of Ampicillin-Loaded Whitlockite for Bone Regeneration.

Introduction Whitlockite (WH), a rare phosphate mineral within the apatite group, shows potential for bone regeneration owing to its superior composition and biocompatibility compared to hydroxyapatite. It can serve as a carrier for bioactive molecules, gradually releasing them to stimulate bone growth and expedite healing. This study aims to assess the biocompatibility of antibiotic-loaded WH, focusing on ampicillin, for bone regeneration applications. Methodology WH particles loaded with varying concentrations of ampicillin (10 and 25 mM) underwent biocompatibility assessments using the MTT assay. One gram of particles was incubated in 10 mL of culture medium for 24 and 48 hours. Experimental groups included control, WH, WH with ampicillin at 10 mM (WH+A10), WH with ampicillin at 25 mM (WH+A25), and positive control treated with 0.1% Triton X detergent. Subsequently, after a three-day culture period, RunX2 gene expression, indicative of osteoblastic differentiation, was quantified using real-time PCR analysis. Results Our research evaluated the bioactivity of WH particles treated with human osteoblastic cells using the MTT assay. While 10 mM ampicillin-loaded WH showed no significant difference in metabolic activity at both 24 and 48 hours, 25 mM ampicillin-loaded WH exhibited a slight reduction in metabolic activity at 24 hours, which normalized by 48 hours. Additionally, we assessed osteogenic potential and showed a significant increase in RunX2 expression with ampicillin-loaded WH, indicating sustained osteogenic properties. Conclusions Our study underscores the promising biocompatibility of WH particles by retaining their osteogenic properties even when, loaded with ampicillin, offering a potential avenue for future bone regeneration strategies.

Exploration of Antimicrobial Peptides in the Treatment of Gentamicin-Resistant Klebsiella pneumoniae Infection.

Introduction: The emergence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) and the decline of effective antibiotics lead to the urgent need for new antibacterial agents. The aim of this study is to investigate the therapeutic effect of antimicrobial peptides against gentamicin-resistant (RT) K. pneumoniae and to screen effective antimicrobial peptides. Methods: In this study, the RT strains were induced by gradient gentamicin, and the RT strains were selected by detecting the expression levels of efflux pump genes, porin genes, and biofilm formation genes of the strains combined with their effects on the cells. Then the effects of four antimicrobial peptides on the efflux pump activity, biofilm formation level and cell condition after infection were detected to explore the effects of antimicrobial peptides on RT strains. Finally, the RT strain was used to induce a mouse model of pneumonia, and the four antimicrobial peptides were used to treat pneumonia mice for in vivo experiments. The pathological changes in lung tissues in each group were detected to explore the antimicrobial peptide with the most significant effect on the RT strain in vivo. Results: The results showed that the minimal inhibitory concentrations of the RT strains (strain C and strain I) were significantly higher than those of the wild-type strain, and the expression of efflux pump, porin and biofilm formation genes was significantly increased. The antimicrobial peptides could effectively inhibit the biofilm formation and efflux pump protein function of the RT strains. In addition, the antimicrobial peptides showed promising antibacterial effects both in vitro and in vivo. Discussion: Our study provided a theoretical basis for the treatment of gentamicin resistant K. pneumoniae infection with antimicrobial peptides, and found that KLA was significantly superior to LL37, Magainin I, KLA and Dermaseptin (10 µg/mL in cells, 50 µg in mice).

Retrospective study in 1020 cases on the rate of surgical site infections after lacrimal surgery without prophylactic systemic antibiotics.

BACKGROUND/AIMS: Data regarding the effectiveness of prophylactic systemic antibiotics (PSA) in lacrimal surgery is scarce. Therefore, we determined the postoperative surgical site infection (SSI) rate in lacrimal surgery without PSA. METHODS: We retrospectively analysed files of patients who underwent external (extDCR) or endoscopic endonasal dacryocystorhinostomy (endoDCR). We excluded patients with incomplete data (n = 68), acute a priori infection with the need for antibiotics (n = 15) and PSA post-operatively for other reasons (n = 28). Indications for surgery were canalicular stenosis (n = 51, 18.6% endoDCR vs n = 131, 19.5% extDCR), nasolacrimal duct obstruction (n = 118, 43.2% endoDCR vs n = 480, 64.3% extDCR) and mucocele/chronic dacryocystitis (n = 52, 19.0% endoDCR vs n = 187, 25.0% extDCR). RESULTS: In this study, 1020 DCR surgeries were performed in 899 patients. Postoperative SSI was diagnosed in eight patients (0.8%); exclusively after extDCR (1.1% of all extDCR). No SSIs were found in endoDCR cases. The prevalence between SSI in extDCR versus endoDCR did not prove significant (n = 8/747 0.8% vs n = 0/273 0%, p = 0.13). All patients diagnosed with SSI were successfully treated with systemic oral antibiotics. CONCLUSION: The prevalence of SSI after DCR is low and was effectively treated with oral antibiotics. In our study, SSI occurred rarely after extDCR and was not observed after endoDCR. We conclude that lacrimal surgery is safe without the routine administration of PSA.

The Enigma of Recurrent Lung Abscess: Management and Outcomes in a School-Aged Child With a Review of Literature.

Pediatric lung abscess is a rare and poorly studied disease entity. In the past, prolonged courses of intravenous (IV) antibiotics have been successfully used; however, with the advent of interventional radiology, the main therapeutic approach is through percutaneous placement of pigtail catheters with ultrasound and computed tomography (CT) direction, where available. The pathogen yield identified from fluid samples of the abscess has dramatically increased owing to the greater invasive measures, such as aspiration and drainage, as well as enhanced microbiological diagnostic methods, which also include polymerase chain reaction testing. In our case report, in 2012 when the patient was two years old, she was diagnosed with pulmonary Koch's and underwent anti-Koch's therapy, category 2. High-resolution CT of the chest revealed a large lobulated cavitary lesion with an air-fluid level suggestive of a right lung abscess. After initial therapy with IV antibiotics for three weeks and a negative tuberculosis work-up, she underwent right limited lateral thoracotomy and drainage with decortication of the right lung abscess (LA) in 2019 via a left endobronchial tube with a bronchial blocker (general endobronchial anesthesia). All samples sent for histopathologic examination after surgery yielded negative results, and she was discharged after a course of injectable antibiotics for 21 days. She remained almost symptom-free for the next four years. Thereafter, she presented with a right LA recurrence due to a thick-walled cavitary lesion, with a severely damaged right lower lung lobe resulting in right lower lobectomy under single-lung ventilation (double-lumen endotracheal tube No. 26 Fr.). Culture results should guide management, particularly for immunocompromised patients, as the LA may be attributed to complications arising from underlying conditions. Primary lung abscesses (PLA) in children are typically caused by Staphylococcus aureus, Streptococcal species, and Klebsiella pneumoniae. Compared to adults, children with PLA and secondary lung abscesses have a meaningfully greater rate of recovery.

Assessing Morinidazole for Surgical Site Infection in Class â ¢ Wounds Prevention: A Multicenter, Randomized, Single-Blind, Parallel-Controlled Study.

INTRODUCTION: Surgical site infections are significant postoperative risks, antibiotic prophylaxis is crucial due to the presence of anaerobic bacteria. This study investigated the efficacy and safety of a novel nitroimidazole, morinidazole, in SSI reduction in class Ⅲ wounds, as there is currently a lack of evidence in the existing literature. METHODS: A multicenter randomized clinical trial was conducted from December 2020 to October 2022 in the general surgery departments of 12 tertiary hospitals in China. 459 patients in two treatment groups using morinidazole plus ceftriaxone or ceftriaxone alone. Efficacy and safety were evaluated including SSI incidence, adverse events, and compliance. Statistical analysis employed SAS 9.4 software. Data analysis was performed from February to May 2023. RESULTS: A total of 440 participants (median [IQR] age, 63.0 [54.0, 70.0] years; 282 males [64.09%]; 437 patients were of Han race [99.32%]) were randomized. The experimental group exhibited a significantly lower SSI rate compared with the control group (31 [14.49%] vs 52 [23.01%]; risk difference, 1.76%, 95%CI, 1.08% to 2.88%; P=0.0224). The superficial incisional site infections revealed a marked reduction in the experimental group (12 [5.61%] vs 31 [13.37%]; risk difference,2.68%; 95%CI,1.34%to5.36%; P=0.0042). Non-surgical site infections, severe postoperative complications, and total adverse events showed no statistically significant differences between the groups (P>0.05). CONCLUSION: The significant decrease in SSI rates and superficial incisional infections demonstrates morinidazole as a valuable prophylactic antibiotic. Our findings provided valuable insights for clinical practice, where this new-generation nitroimidazole can play a crucial role in SSI prevention.

Real-world evidence of systemic treatment practices for biliary tract cancer in Japan: Results of a database study.

PURPOSE: To describe the real-world treatment patterns of systemic therapies for biliary tract cancer (BTC) and to examine the frequency and management of biliary infection in Japan. METHODS: Patients diagnosed with BTC and prescribed systemic therapy between January 2011 and September 2020 were retrieved from the Japanese Medical Data Vision database. The look-back period was set to 5 years. Patient characteristics, treatment patterns, and biliary infection-induced treatment interruption were analyzed. RESULTS: The full analysis set comprised 22 742 patients with a mean age of 71.0 years and 61.6% were male. The most common BTC type was extrahepatic cholangiocarcinoma (44.6%). The three most common first-line regimens were S-1 monotherapy (33.0%), gemcitabine+cisplatin (32.5%), and gemcitabine monotherapy (18.7%) over the entire observation period (January 2011-September 2021). Patients who received monotherapies tended to be older. Biliary infection-induced treatment interruption occurred in 29.5% of patients, with a median time to onset of 64.0 (interquartile range 29.0-145.0) days. The median duration of intravenous antibiotics was 12.0 (interquartile range 4.0-92.0) days. CONCLUSIONS: These results demonstrated potential challenges of BTC in Japanese clinical practice particularly use of multiple regimens, commonly monotherapies, which are not recommended as first-line treatment, and the management of biliary infections during systemic therapy.

Quantitative analysis of the impact of infectious disease physicians on patients in the emergency department fast-track parenteral antibiotics program.

INTRODUCTION: The outpatient parenteral antibiotic therapy (OPAT) program of Vancouver General Hospital (VGH) was supervised by emergency physicians (EPs) until 2017 when infectious disease (ID) physicians began assisting in management. We designed a retrospective study to determine whether ID involvement led to improved outcomes. METHODS: This study analyzes the impact of ID involvement by comparing the mean days patients spent on OPAT with ID involvement versus EPs alone through a retrospective chart review. Secondary research objectives were to compare patient care decisions, e.g., antibiotic choice, tests ordered, and final diagnosis. RESULTS: There was no difference between the mean number of days on OPAT between physician types. Compared to historic patterns, patients seen in OPAT after increased ID consultation spent an average of 0.5 fewer days in the program. However, when grouped by the first day of ID assessment, the average total days in OPAT was closely aligned with the day of first ID assessment, implying that ID frequently discharged patients close to initial assessment. Patients seen by ID were less likely to return within one month of discharge compared to those not seen by ID. Secondary findings include ID physicians prescribing a greater range of antibiotics, providing more varied final diagnoses, prescribing antibiotics less frequently, as well as ordering more cultures, diagnostic imaging and specialist consults. DISCUSSION: The findings of this study support the hypothesis that ID involvement in OPAT programs leads to changes in care that may have beneficial outcomes for patients and the healthcare system.

Epidemiology and antimicrobial resistance of Mycobacterium spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.

Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.

Subminimum Inhibitory Concentrations Tetracycline Antibiotics Induce Biofilm Formation in Minocycline-Resistant Klebsiella pneumonia by Affecting Bacterial Physical and Chemical Properties and Associated Genes Expression.

Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased. Under sub-MICs of tetracycline antibiotics treatment, abnormal stretching of bacteria was observed by scanning electron microscopy. Treatment with sub-MICs of tetracyclines leads to increased surface hydrophobicity and eDNA content and decreased outer membrane permeability. The expression levels of the fimA, luxS, qseB, and qseC genes decreased, the expression level of mrkA increased, and the expression level of acrA was inconsistent under different tetracycline antibiotics treatments. Together, our results suggested that the increase in Klebsiella pneumoniae biofilm formation caused by sub-MICs of tetracycline antibiotics may occur by affecting bacterial physical and chemical properties and associated genes expression.

PBI derivatives/surfactant-based fluorescent ensembles: Sensing of multiple aminoglycoside antibiotics and interaction mechanism studies.

Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.

Potential barriers to the rational antibiotic use in dental and periodontal practice: A questionnaire-based online survey.

BACKGROUND: Dentists, through inappropriate antibiotic prescription, may contribute to the global problem of antibiotic resistance (AR). OBJECTIVES: Understanding dentists' antibiotic prescription patterns, source of knowledge, and the driving forces behind their prescription practices may be crucial for the effective implementation of the rational use of antibiotics (RUA) in dentistry. MATERIAL AND METHODS: Active members of the Turkish Dental Association were invited to participate in an electronic survey comprising questions focusing on their role, knowledge and perceptions regarding RUA, the perceived barriers to adapting RUA in daily dental work, and the actual antibiotic prescription practices. The potential impact of age, gender, professional experience, and the mode of dental practice was also evaluated. Dentists' prescription practices for periodontal disease/conditions were evaluated as well. RESULTS: Based on 1,005 valid responses, there was consensus on the necessity of RUA (99.1%); however, its implementation was low. The main barriers were dentists' own safety concerns (74.4%), strong patients' demands (42.2%) and the fact that prescribing antibiotics became a professional habit (35.8%). Different educational background resulted in clear variances in everyday prescription practices. CONCLUSIONS: The implementation of RUA was not sufficient and the perceived barriers had an impact on daily prescribing habits. Support for dental professionals through the efficient dissemination of evidencebased clinical guidelines and decision-making aids is likely to require additional help from professional organizations in order to actively combat AR.

Environmental risk and market approval for human pharmaceuticals.

This paper contributes to the growing discussion about how to mitigate pharmaceutical pollution, which is a threat to human, animal, and environmental health as well as a potential driver of antimicrobial resistance. It identifies market approval of pharmaceuticals as one of the most powerful ways to shape producer behavior and highlights that applying this tool raises ethical issues given that it might impact patients' access to medicines. The paper identifies seven different policy options that progressively give environmental considerations increased priority in the approval process, identifies ethically relevant interests affected by such policies, and makes explicit tensions and necessary tradeoffs between these interests. While arguing that the current European regulation gives insufficient weight to environmental considerations, the paper highlights concerns with the strongest policy options, on the grounds that these may very well endanger patients' access to effective medication.