Pharmacological induction of diabetes mellitus in pregnant female mice: a comparison of two doses and routes of administration.

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.

Retrospective comparison between low-volume high-concentration and high-volume low-concentration levobupivacaine for bilateral erector spinae plane block in dogs undergoing hemilaminectomy.

OBJECTIVE: To compare the analgesic effect of a bilateral ultrasound-guided erector spinae plane block (ESPB) in dogs undergoing hemilaminectomy using either a low-volume high-concentration (LV-HC) or a high-volume low-concentration (HV-LC) local anaesthetic solution. STUDY DESIGN: Retrospective observational equivalence trial. ANIMALS: A total of 391 client-owned dogs undergoing hemilaminectomy. METHODS: Dogs were assigned to group LV-HC or HV-LC depending on whether 0.2-0.25% levobupivacaine (0.4-0.5 mL kg-1) or 0.125-0.15% levobupivacaine (0.8-1 mL kg-1) was used to perform the ESPB, respectively. The number of dogs in which intraoperative rescue fentanyl boluses were administered, the total dose of fentanyl administered, the overall methadone consumption during the first 24 hours postoperatively and anaesthetic complications were recorded. Univariate and multivariate statistical analyses were performed considering p < 0.05 significant. RESULTS: A total of 248 and 143 dogs were assigned to groups LV-HC and HV-LC, respectively. In group HV-LC, the number of dogs requiring fentanyl intraoperatively (64.3%) was higher (p = 0.0001) than that in group LV-HC (43.5%). The overall intraoperative fentanyl consumption was higher in group HV-LC between the first skin incision and the end of the lamina drilling (p = 0.028). According to the regression analysis, the group allocation was the best variable to predict the intraoperative fentanyl consumption (p < 0.001). Antimuscarinic drugs were administered more frequently in group LV-HC (p < 0.02). However, the prevalence of hypotension and other pharmacological cardiovascular interventions did not differ between groups. No differences in methadone consumption during the first 24 hours postoperatively were found between the groups. CONCLUSIONSAND CLINICAL RELEVANCE: When performing a bilateral ESPB in dogs undergoing hemilaminectomy, compared with HV-LC, the use of LV-HC local anaesthetic solution reduces the intraoperative fentanyl consumption without affecting the postoperative methadone requirement.

Fungal removal of cyanotoxins in constructed wetlands: The forgotten degraders.

Harmful cyanobacterial blooms have increased globally, releasing hazardous cyanotoxins that threaten the safety of water resources. Constructed wetlands (CWs) are a nature-based and low-cost solution to purify and remove cyanotoxins from water. However, bio-mechanistic understanding of the biotransformation processes expected to drive cyanotoxin removal in such systems is poor, and primarily focused on bacteria. Thus, the present study aimed at exploring the fungal contribution to microcystin-LR and cylindrospermopsin biodegradation in CWs. Based on CW mesocosms, two experimental approaches were taken: a) amplicon sequencing studies were conducted to investigate the involvement of the fungal community; and b) CW fungal isolates were tested for their microcystin-LR and cylindrospermopsin degradation capabilities. The data uncovered effects of seasonality (spring or summer), cyanotoxin exposure, vegetation (unplanted, Juncus effusus or Phragmites australis) and substratum (sand or gravel) on the fungal community structure. Additionally, the arbuscular mycorrhizal fungus Rhizophagus and the endophyte Myrmecridium showed positive correlations with cyanotoxin removal. Fungal isolates revealed microcystin-LR-removal potentials of approximately 25 % in in vitro biodegradation experiments, while the extracellular chemical fingerprint of the cultures suggested a potential intracellular metabolization. The results from this study may help us understand the fungal contribution to cyanotoxin removal, as well as their ecology in CWs.

Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology's Headache Study Group.

Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice. This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.

Inflammatory lesions of the brainstem: Keys for the diagnosis by MRI.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings for the most common inflammatory and immune-mediated diseases that involve the brainstem. CONCLUSION: Inflammatory lesions involving the brainstem are associated with a wide range of autoimmune, infectious, and paraneoplastic syndromes, making the differential diagnosis complex. Being familiar with these entities, their clinical characteristics, and their manifestations on MRI, especially the number of lesions, their shape and extension, and their appearance in different sequences, is useful for orienting the radiological diagnosis.

The impact of non-neutral synonymous mutations when inferring selection on non-synonymous mutations.

The distribution of fitness effects (DFE) describes the proportions of new mutations that have different effects on reproductive fitness. Accurate measurements of the DFE are important because the DFE is a fundamental parameter in evolutionary genetics and has implications for our understanding of other phenomena like complex disease or inbreeding depression. Current computational methods to infer the DFE for nonsynonymous mutations from natural variation first estimate demographic parameters from synonymous variants to control for the effects of demography and background selection. Then, conditional on these parameters, the DFE is then inferred for nonsynonymous mutations. This approach relies on the assumption that synonymous variants are neutrally evolving. However, some evidence points toward synonymous mutations having measurable effects on fitness. To test whether selection on synonymous mutations affects inference of the DFE of nonsynonymous mutations, we simulated several possible models of selection on synonymous mutations using SLiM and attempted to recover the DFE of nonsynonymous mutations using Fit∂a∂i, a common method for DFE inference. Our results show that the presence of selection on synonymous variants leads to incorrect inferences of recent population growth. Furthermore, under certain parameter combinations, inferences of the DFE can have an inflated proportion of highly deleterious nonsynonymous mutations. However, this bias can be eliminated if the correct demographic parameters are used for DFE inference instead of the biased ones inferred from synonymous variants. Our work demonstrates how unmodeled selection on synonymous mutations may affect downstream inferences of the DFE.

Cyanobacterial blooms in surface waters - Nature-based solutions, cyanotoxins and their biotransformation products.

Cyanobacterial blooms are expected to become more frequent and severe in surface water reservoirs due to climate change and ecosystem degradation. It is an emerging challenge that especially countries relying on surface water supplies will face. Nature-based solutions (NBS) like constructed wetlands and biofilters can be used for cyanotoxin remediation. Both technologies are reviewed and critically assessed for different types of water resources. The available information on cyanotoxins (bio)transformation products (TPs) is reviewed to point out the potential research gaps and to disclose the most reliable enzymatic degradation pathways. Knowledge gaps were found, such as information on the performance of the revised NBS in pilot and full scales, the removal processes covering different cyanotoxins (besides the most widely studied microcystin-LR), and the difficulties for real-world implementation of technologies proposed in the literature. Also, most studies focus on bacterial degradation processes while fungi have been completely overlooked. This review also presents an up-to-date overview of the transformation of cyanotoxins, where degradation product data was compiled in a unified library of 22 metabolites for microcystins (MCs), 7 for cylindrospermopsin (CYN) and 10 for nodularin (NOD), most of them reported only in a single study. Major gaps are the lack of environmentally relevant studies with TPs in pilot and full- scale treatment systems, information on TP's toxicity, as well as limited knowledge of environmentally relevant degradation pathways. NBS have the potential to mitigate cyanotoxins in recreational and irrigation waters, enabling the water-energy-food nexus and avoiding the degradability of the ecosystems.

Constructed wetland mesocosms improve the biodegradation of microcystin-LR and cylindrospermopsin by indigenous bacterial consortia.

Cyanobacterial blooms releasing harmful cyanotoxins, such as microcystin (MC) and cylindrospermopsin (CYN), are prominent threats to human and animal health. Constructed wetlands (CW) may be a nature-based solution for bioremediation of lake surface water containing cyanotoxins, due to its low-cost requirement of infrastructure and environmentally friendly operation. There is recent evidence that microcystin-LR (MC-LR) can efficiently be removed in CW microcosms where CYN degradation in CW is unknown. Likewise, the mechanistic background regarding cyanotoxins transformation in CW is not yet elucidated. In the present study, the objective was to compare MC-LR and CYN degradation efficiencies by two similar microbial communities obtained from CW mesocosms, by two different experiments setup: 1) in vitro batch experiment in serum bottles with an introduced CW community, and 2) degradation in CW mesocosms. In experiment 1) MC-LR and CYN were spiked at 100 µg L-1 and in experiment 2) 200 µg L-1 were spiked. Results showed that MC-LR was degraded to ≤1 µg L-1 within seven days in both experiments. However, with a markedly higher degradation rate constant in the CW mesocosms (0.18 day-1 and 0.75 day-1, respectively). No CYN removal was detected in the in vitro incubations, whereas around 50 % of the spiked CYN was removed in the CW mesocosms. The microbial community responded markedly to the cyanotoxin treatment, with the most prominent increase of bacteria affiliated with Methylophilaceae (order: Methylophilales, phylum: Proteobacteria). The results strongly indicate that CWs can develop an active microbial community capable of efficient removal of MC-LR and CYN. However, the CW operational conditions need to be optimized to achieve a full CYN degradation. To the best of our knowledge, this study is the first to report the ability of CW mesocosms to degrade CYN.

Production of poly-3-hydroxybutyrate (PHB) nanoparticles using grape residues as the sole carbon source.

The production of poly-3-hydroxybutyrate (PHB) on an industrial scale remains a major challenge due to its higher production cost compared to petroleum-based plastics. As a result, it is necessary to develop efficient fermentative processes using low-cost substrates and identify high-value-added applications where biodegradability and biocompatibility properties are of fundamental importance. In this study, grape residues, mainly grape skins, were used as the sole carbon source in Azotobacter vinelandii OP cultures for PHB production and subsequent nanoparticle synthesis based on the extracted polymer. The grape residue pretreatment showed a high rate of conversion into reducing sugars (fructose and glucose), achieving up to 43.3 % w w-1 without the use of acid or external heat. The cultures were grown in shake flasks, obtaining a biomass concentration of 2.9 g L-1 and a PHB accumulation of up to 37.7 % w w-1. PHB was characterized using techniques such as Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The formation of emulsified PHB nanoparticles showed high stability, with a particle size between 210 and 240 nm and a zeta potential between -12 and - 15 mV over 72 h. Owing to these properties, the produced PHB nanoparticles hold significant potential for applications in drug delivery.

Clinical findings, surgical treatment and outcome in dogs with parotid duct ectasia: 14 cases (2010-2023).

OBJECTIVES: To describe the clinical presentation, diagnostic findings, surgical treatment and outcome of dogs diagnosed with parotid duct ectasia. MATERIALS AND METHODS: Medical records of dogs diagnosed with parotid duct ectasia between 2010 and 2023 at six small animal referral hospitals were retrospectively reviewed. Outcome was assessed by contacting the owners or referring veterinarians. RESULTS: Fourteen dogs were included. Lateral facial swelling was the most common clinical presentation. CT revealed a tortuous cavitary tubular fluid-filled structure consistent with a dilated parotid duct in all dogs. Surgical treatment included marsupialisation of the parotid duct papilla, surgical exploration of the duct alone, parotid duct marsupialisation with surgical exploration of the duct, parotidectomy or en-bloc parotid duct resection. The aetiology of parotid duct ectasia was not established in 13 of 14 dogs. In one case, a foreign body was retrieved from the duct. No recurrence of clinical signs was noted during the follow-up period (range 21 to 2900 days). CLINICAL SIGNIFICANCE: Parotid duct ectasia should be considered for dogs with a lateralised fluctuant non-painful tubular facial swelling. Surgical management was associated with a favourable prognosis without evidence of recurrence in all cases reported in the case series.

Acquired perforating dermatosis in patients on peritoneal dialysis: a report of 3 cases.

Background: Acquired perforating dermatosis (APD) is a heterogeneous group of unfrequented diseases (2.5 cases for 100,000 habitants) associated with multiple pathologies like end-stage renal disease and other concomitant conditions such as diabetes mellitus (DM). Case Description: We described 3 cases of APD in patients on peritoneal dialysis (PD), one of them with a giant variant of reactive perforating collagenosis (RPC). The first case is a 28-year-old man with chronic kidney disease on PD and a lousy control of disturbances of calcium and phosphorus metabolism that develops an APD. The second case is a 44-year-old man with DM, chronic kidney disease (CKD) on PD, and poor control of disturbances of calcium and phosphorus metabolism that develops an RPC. The third case is a 58-year-old man with DM, rheumatoid arthritis, hypothyroidism, CKD and bad control of calcium and phosphorus metabolism that develops a giant variant of RPC with poor evolution. Conclusions: CKD and concomitant conditions such as DM present an increased risk of developing APD. Poor control of calcium and phosphorus metabolism is frequently found in patients with CKD and seems to be related to the development of APD in our cases. With the description of these cases, we want to emphasize the importance of knowing this rare disease, in order to promptly refer to Dermatology and start treatment.

Tailored Prevention of Functional Decline through a Multicomponent Exercise Program in Hospitalized Oncogeriatric Patients: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.

[Type 3 c diabetes: Approach from the first level doctor]. / La diabetes tipo 3c. Abordaje desde el médico del primer nivel.

DM3c is diabetes (DM) of the exocrine pancreas that must be suspected whenever there is a history of chronic pancreatitis (CP), acute pancreatitis (AP) or recurrence (80% of cases) or new-onset DM in individuals from over 50 years of age without any other justification (negative autoimmunity tests, Glutamic Acid Decarboxylase antibodies). It is an entity misdiagnosed as type 2 diabetes (DM2) (90%) and therefore, if it is not suspected, it can go unnoticed. For its diagnosis, abdominal ultrasound, determination of the CA 19.9 tumor antigen (carbohydrate antigen 19-9), nuclear magnetic resonance (NMR) or computerized axial tomography (CT) are useful. The treatment is the same as DM2, although certain specifications depend on the type of drugs and with the particularity that in dealing with «fragile diabetes¼ greater caution must be taken with hypoglycemia (monitoring). Likewise, as it is a disease of the exocrine pancreas, it will have to be specifically treated to avoid metabolic, malabsorptive and/or nutritional alterations.

[Translated article] Tumor ablation and vertebral augmentation in the treatment of vertebral metastases: A multicenter study.

INTRODUCTION: Treatment of metastatic vertebral fractures without neural compression is performed with percutaneous cementation techniques. The increase in intratumoral pressure by these techniques can send tumor cells into the bloodstream. To prevent this dissemination and improve pain treatment, ablation techniques have been introduced that would allow the creation of a cavity in the tumor prior to cementation or directly necrosing the metastasis when its size is small. MATERIAL: We present the experience with ablation of two hospitals and two different ablation techniques. The first group used radiofrequency ablation (A) in 14 patients (26 vertebrae), 4 of whom underwent vertebral arthrodesis. The second group used microwave ablation (B) in 93 patients (129 lesions) without associated vertebral instrumentation. RESULTS: In group A pain improvement in VAS was 7.7-2.6 at 6 weeks. There were no complications derived from the ablation. In most cases cementation was associated. In the group B pain improvement in VAS went from 6.8 to 1.7 at 6 weeks. Cementation was associated in all cases. There were no complications derived from the ablation. CONCLUSION: The association of ablation techniques with vertebral cementation is a safe technique that significantly improves the patient's pain and can help control the disease.

Major Fusarium species and mycotoxins associated with freshly harvested maize grain in Uruguay.

Fusarium species are common fungal pathogens of maize. Fusarium graminearum and Fusarium verticillioides, among others, can cause maize ear rot, and they are also mycotoxin producers. The aims of this work were to determine the frequency and diversity of Fusarium species in Uruguayan maize kernels, evaluate the toxigenic potential of the isolates, determine toxin contamination levels on freshly harvested grain, and assess the sensitivity of main Fusarium species against fungicides. Fusarium verticillioides was the most frequent species isolated, followed by Fusarium graminearum sensu stricto. Of F. verticillioides isolates studied for fumonisin production, 72% produced fumonisin B1 and 32% fumonisin B2. Considering in vitro toxin production by F. graminearum sensu stricto isolates, deoxynivalenol was the main toxin produced, followed by zearalenone and nivalenol. Fumonisins were the most frequently found toxins on freshly harvested maize samples (98% in 2018 and 86% in 2019), and also, fumonisin B1 was the toxin with highest concentration in both years studied (4860 µg/kg in 2018 and 1453 µg/kg in 2019). Deoxynivalenol and zearalenone were also found as contaminants. Metconazole and epoxiconazole were the most effective fungicides tested on F. verticillioides isolates. Fusarium graminearum sensu stricto isolates also were more sensitive to metconazole compared to other fungicides; nevertheless, epoxiconazole was less efficient in controlling this species. This is the first study that reports Fusarium species and mycotoxin contamination levels associated with maize grain in Uruguay. Its detection is the main step to develop management strategies in order to minimize fungal infection in maize crops.

The importance of prevalence and pre-test probability on the microbiological diagnosis of SARS-CoV-2: the case of Spain in 2020.

OBJECTIVE: The aim of this work was to estimate the conditioned probability for the diagnosis of SARS-CoV-2 infection with reverse transcription polymerase chain reaction (RT-PCR), viral antigen rapid diagnostic tests (Ag-RDT), and antibody detection tests depending on the prevalence in the specific healthcare settings in Spain in 2020, and on the pre-test probability (PTP) according to the clinical situation, age and unknown or close contacts of the patient. METHODS: Performance parameters of tests were obtained from literature. Prevalence data and PTP were obtained from Spanish sources and a survey, respectively. The post-test probability is the positive predictive value (PPV) when test is positive. For negative result, we also calculated the probability of having the infection (false negatives). RESULTS: For both RT-PCR and viral Ag-RDT, the lowest PPV values were for the population screenings. This strategy proved to be useful in ruling out infection but generates a high number of false positives. At individual level, both tools provided high PPV (≥ 97%) when the PTP values are over 35%. In seroprevalence studies, though the specificity of IgG alone tests is high, under low seroprevalence, false positives cannot be avoided. Total antibodies tests are useful for diagnosis of COVID-19 in those doubtful cases with RT-PCR or Ag-RDT tests being repeatedly negative. CONCLUSIONS: The interpretating of results depends not only on the accuracy of the test, but also on the prevalence of the infection in different settings, and the PTP associated to the patient before performing the test.

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost.

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20-30 nm, being in vitro tolerance within 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4-6 days without polymer and 9-13 days with polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

Consumption of commercially sold dried fish snack "Charales" contaminated with microplastics in Mexico.

Inadvertent human exposure to microplastics by the ingestion of microplastic-contaminated processed foods poses health risks and new preventative issues; nevertheless, investigations analyzing microplastic occurrences in commercially dried fish for direct human consumption are scarce. This study assessed the abundance and characteristics of microplastics in 25 commercially sold dried fish products (4 supermarkets, 3 street vendors, and 18 traditional agri-product farmers' markets) from two widely consumed and commercially important Chirostoma species (C. jordani and C. patzcuaro) in Mexico. Microplastics were detected in all the samples examined, with abundances ranging from 4.00 ± 0.94 to 55.33 ± 9.43 items g-1. C. jordani dried fish samples had higher mean microplastic abundance (15.17 ± 5.90 items g-1) than the C. patzcuaro dried fish samples (7.82 ± 2.90 items g-1); nevertheless, there was no statistically significant difference in microplastic concentrations between the samples. The most prevalent type of microplastic was fiber (67.55%), followed by fragment (29.18%), film (3.00%), and sphere (0.27%). Non-colored microplastics (67.35%) predominated, while microplastic sizes varied from 24 to 1670 µm, with sizes less than 500 µm (84%) being the most common. ATR-FTIR analysis revealed polyester, acrylonitrile butadiene styrene, polyvinyl alcohol, ethylene-propylene copolymer, nylon-6 (3), cellophane, and viscose in the dried fish samples. Overall, this study's findings are the first in Latin America to demonstrate microplastic contamination in dried fish for human consumption, underscoring the need for developing countermeasures to prevent plastic pollution in fish-caught regions and reduce the risks of human exposure to these micropollutants.