The freshwater isopod Asellus aquaticus as a model biomonitor of environmental pollution: A review

Anthropogenic substances pollute freshwater systems worldwide, with serious, long-lasting effects to aquatic biota. Present methods of detecting elevated levels of trace metal pollutants are typically accurate but expensive, and therefore not suitable for applications requiring high spatial resolution. Additionally, these methods are not efficient solutions for the determination of long-term averages of pollution concentration. This is the rationale for the implementation of a biomonitoring programme as an alternative means of pollutant detection. This review summarises recent literature concerning the past and potential uses of the benthic isopod Asellus aquaticus as a biomonitor for pollution in freshwater systems. Recent studies indicate that A. aquaticus is well suited for this purpose. However, the mechanisms by which it bioaccumulates toxins have yet to be fully understood. In particular, the interactions between coexisting trace metal pollutants in the aquatic environment have only recently been considered, and it remains unclear how a biomonitoring programme should adapt to the effects of these interactions. It is evident that failing to account for these additional stressors will result in an ineffective biomonitoring programme; for this reason, a comprehensive understanding of the bioaccumulation mechanisms is required in order to reliably anticipate the effects of any interferences on the outcome

Application of broadband acoustic resonance dissolution spectroscopy (BARDS) to the gas release behaviour during rehydration of milk protein isolate agglomerates

peer-reviewedThe BARDS technique was applied in this study to acoustically assess the rehydration behaviour of milk protein isolate (MPI) agglomerates and to compare with regular MPI powder. The results showed that BARDS has potential to monitor the rehydration behaviour of agglomerates. The greater porosity (>70%) of agglomerated powders introduced more compressible gas into the water. The BARDS profile showed that there was faster initial gas release from the agglomerates, indicating better wetting and dispersion ability of the agglomerates with shorter tM (time of maximum gas volume in solution). At 0.10% powder addition, agglomerated MPI reached tM within 109 s, which was significantly less than the control MPI at 140 s. MPI with lactose binder (MPI-L) had a tM of 80 s at 0.10% powder addition and, larger size MPI-L had a tM of 60 s. At 0.20% and 0.30% powder addition, more time was required to wet and disperse the powders

Contactless, probeless and non-titrimetric determination of acid-base reactions using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

pH determination is a routine measurement in scientific laboratories worldwide. Most major advances in pH measurement were made in the 19th and early 20th century. pH measurements are critical for the determination of acid base reactions. This study demonstrates how an acid-base reaction can be monitored without the use of a pH probe, indicator and titres of reagent. The stoichiometric reaction between carbonate and HCl acid yields specific quantities of CO2, which causes reproducible changes to the compressibility of the solvent. This in turn slows down the speed of sound in solution which is induced by a magnetic follower gently tapping the inner wall of the vessel. As a consequence the frequencies of the acoustic resonances in the vessel are reduced. This approach is called Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) which harnesses this phenomenon for many applications. The acid-carbonate experiments have also been validated using H2SO4 acid and using both potassium and sodium counterions for the carbonate. This method can be used to interrogate strong acid-base reactions in a rapid and non-invasive manner using carbonate as the base. The data demonstrates the first example of a reactant also acting as an indicator. The applicability of the method to weak acids has yet to be determined. A novel conclusion from the study is that a person with a well-trained ear is capable of determining the concentration and pH of a strong acid just by listening. This brings pH measurement into the realm of human perception

The sound of salts by Broadband Acoustic Resonance Dissolution Spectroscopy

Salts are available in different grades and in a wide price range. Some contain more impurities than others, while some have special culinary traits that determine their identity. Acoustic profiling, which is based on the ‘hot chocolate effect’, may provide an interesting strategy to characterise salts of various origins to underpin their identity. In this study, the link between the identity of 60 food grade and technical salts and their acoustic properties was examined by Broad Acoustic Resonance Dissolution Spectroscopy. In particular, the influence of the composition of the salts and the impact of the salts' particle size distributions on their acoustic profiles were examined. Sodium and potassium contents were measured by flame photometry and the salts' particle size distributions by laser light diffraction. Reference salts (NaCl, KCl, MgCl2) and mixtures thereof were analysed for comparison, as well as intact and ground versions of the salt samples. The results show that both the composition and morphology of the salt crystals determine the down-slope of the resonance frequency, which is caused by the rate of release of entrained and dissolved gas. Coarse salts with high levels of non-NaCl constituents showed a rapid decline in sound frequency, which corresponds to a high gas release rate. On the other hand fine salts composed of pure NaCl revealed a slower change in sound frequency and thus lower gas release rates. The frequency minimums were however not affected by the salts' compositions nor particle size distributions. It is primarily the particle size distribution that affects the rate at which gas is released, and thus the change in sound frequency. Only when the particles are more similar in size, the composition also starts playing a role. Since both particle size distribution and composition is unique for each salt, the various salts show distinct acoustic profiles. Evidently, the current study shows that ‘listening’ to the sound of salts reveals interesting information about their identity and origin

Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): a rapid test for enteric coating thickness and integrity of controlled release pellet formulations

There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC

Tracking yeast metabolism and the Crabtree effect in real time via CO2 production using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

In this study, a new approach to measure metabolic activity of yeast via the Crabtree effect is described. BARDS is an analytical technique developed to aid powder and tablet characterisation by monitoring changes in the compressibility of a solvent during solute dissolution. It is a rapid and simple method which utilises a magnetic stir bar to mix added solute and induce the acoustic resonance of a vessel containing a fixed volume of solvent. In this study it is shown that initiation of fermentation in a yeast suspension, in aqueous buffer, is accompanied by reproducible changes in the frequency of induced acoustic resonance. These changes signify increased com-pressibility of the suspension due to CO2release by the yeast. A simple standardised BARDS protocol reveals yeast carbon source preferences and can generate quantitative kinetic data on carbon source metabolism which are characteristic of each yeast strain. The Crawford-Woods equation can be used to quantify total gaseous CO2produced by a given number of viable yeast when supplied with a fixed amount of carbon source. This allows for a value to be calculated for the amount of gaseous CO2produced by each yeast cell. The approach has the potential to transform the way in which yeast metabolism is tracked and potentially provide an orthogonal or surrogate method to determining viability, vitality and attenuation measurements in the future

Tracking cocrystallization of active pharmaceutical ingredients with Bbenzoic acid coformer using Broadband Acoustic resonance Dissolution Spectroscopy (BARDS)

This study investigates the use of Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) as a detection method for the formation of cocrystals. BARDS is a novel approach that uses reproducible changes in the compressibility of a solvent as a sample dissolves to characterize and differentiate between materials and in this case cocrystallization. Two cocrystal systems with a 1:1 stoichiometry were examined, which used benzoic acid as a coformer with isonicotinamide and with theophylline. Cocrystals were prepared using dry and wet milling for periods from 1 to 40 min, and samples were analyzed using infrared spectroscopy, powder X-ray diffraction, and BARDS. Comparison of the BARDS data with the IR and PXRD data cross-validated the BARDS results. This study shows that BARDS can be used to rapidly assess the formation of these cocrystals at-line when milling or as a relatively low cost tool in preformulation product development. The data can also be used to gauge the unique entrained gas and gas volume generation of the cocrystal samples during dissolution and their dissolution kinetics

Multidrug-resistant tuberculosis and migration to Europe.

Multidrug-resistant tuberculosis (MDR-TB) in low-incidence countries in Europe is more prevalent among migrants than the native population. The impact of the recent increase in migration to EU and EEA countries with a low incidence of TB (<20 cases per 100 000) on MDR-TB epidemiology is unclear. This narrative review synthesizes evidence on MDR-TB and migration identified through an expert panel and database search. A significant proportion of MDR-TB cases in migrants result from reactivation of latent infection. Refugees and asylum seekers may have a heightened risk of MDR-TB infection and worse outcomes. Although concerns have been raised around 'health tourists' migrating for MDR-TB treatment, numbers are probably small and data are lacking. Migrants experience significant barriers to testing and treatment for MDR-TB, exacerbated by increasingly restrictive health systems. Screening for latent MDR-TB is highly problematic because current tests cannot distinguish drug-resistant latent infection, and evidence-based guidance for treatment of latent infection in contacts of MDR patients is lacking. Although there is evidence that transmission of TB from migrants to the general population is low-it predominantly occurs within migrant communities-there is a human rights obligation to improve the diagnosis, treatment and prevention of MDR-TB in migrants. Further research is needed into MDR-TB and migration, the impact of screening on detection or prevention, and the potential consequences of failing to treat and prevent MDR-TB among migrants in Europe. An evidence-base is urgently needed to inform guidelines for effective approaches for MDR-TB management in migrant populations in Europe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570