Synthesis of mannosylated and PEGylated nanoparticles via RAFT emulsion polymerisation, and investigation of particle-lectin aggregation using turbidimetric and DLS techniques

Recent developments in controlled radical polymerisation presents an attractive way of producing biocompatible polymeric nanoparticles for a wide range of applications. With this motivation, well defined P (ManAm) and P(PEGA) coated nanoparticles in a range of different sizes have been synthesised via RAFT emulsion polymerisation. The particles were used to precisely investigate the effect of particle size on lectin binding with Concanavalin A, and validate the use of online DLS measurements for lectin-glycoparticle aggregation studies. Larger particles were found to have an enhanced aggregation by both UV–Vis turbidimetric and DLS aggregation studies. The DLS technique was shown to be robust up to an aggregate diameter of c.500 nm for aggregation tests, and was not affected by any dilution or light scattering effects that typically hinder the common use of turbidimetry in particle aggregation studies

Do airway metallic stents for benign lesions confer too costly a benefit?

<p>Abstract</p> <p>Background</p> <p>The use of self-expanding metallic stents (SEMAS) in the treatment benign airway obstruction is controversial.</p> <p>Methods</p> <p>To evaluate the safety and efficacy of SEMAS for this indication, we conducted a 10-year retrospective review at our tertiary medical centre.</p> <p>Results</p> <p>Using flexible bronchoscopy, 82 SEMAS (67% Ultraflex, 33% Wallstent) were placed in 35 patients with inoperable lesions, many with significant medical comorbidities (88%). 68% of stents were tracheal, and 83% of patients showed immediate symptomatic improvement. Reversible complications developed in 9% of patients within 24 hrs of stent placement. Late complications (>24 hrs) occurred in 77% of patients, of which 37% were clinically significant or required an interventional procedure. These were mainly due to stent migration (12.2%), fracture (19.5%), or obstructive granulomas (24.4%). The overall granuloma rate of 57% was higher at tracheal sites (59%) than bronchial ones (34%), but not significantly different between Ultraflex and Wallstents. Nevertheless, Wallstents were associated with higher rates of bleeding (5% vs. 30%, p = 0.005) and migration (7% vs. 26%, p = 0.026). Of 10 SEMAS removed using flexible bronchoscopy, only one was associated with incomplete removal of fractured stent wire. Median survival was 3.6 ± 2.7 years.</p> <p>Conclusion</p> <p>Ill patients with inoperable lesions may be considered for treatment with SEMAS.</p

What are the toxicological effects of mercury in Arctic biota?

This review critically evaluates the available mercury (Hg) data in Arctic marine biota and the Inuit population against toxicity threshold values. In particular marine top predators exhibit concentrations of mercury in their tissues and organs that are believed to exceed thresholds for biological effects. Species whose concentrations exceed threshold values include the polar bears (Ursus maritimus), beluga whale (Delphinapterus leucas), pilot whale (Globicephala melas), hooded seal (Cystophora cristata), a few seabird species, and landlocked Arctic char (Salvelinus alpinus). Toothed whales appear to be one of the most vulnerable groups, with high concentrations of mercury recorded in brain tissue with associated signs of neurochemical effects. Evidence of increasing concentrations in mercury in some biota in Arctic Canada and Greenland is therefore a concern with respect to ecosystem health

Revealing the Appetite of the Marine Aquarium Fish Trade: The Volume and Biodiversity of Fish Imported into the United States

The aquarium trade and other wildlife consumers are at a crossroads forced by threats from global climate change and other anthropogenic stressors that have weakened coastal ecosystems. While the wildlife trade may put additional stress on coral reefs, it brings income into impoverished parts of the world and may stimulate interest in marine conservation. To better understand the influence of the trade, we must first be able to quantify coral reef fauna moving through it. Herein, we discuss the lack of a data system for monitoring the wildlife aquarium trade and analyze problems that arise when trying to monitor the trade using a system not specifically designed for this purpose. To do this, we examined an entire year of import records of marine tropical fish entering the United States in detail, and discuss the relationship between trade volume, biodiversity and introduction of non-native marine fishes. Our analyses showed that biodiversity levels are higher than previous estimates. Additionally, more than half of government importation forms have numerical or other reporting discrepancies resulting in the overestimation of trade volumes by 27%. While some commonly imported species have been introduced into the coastal waters of the USA (as expected), we also found that some uncommon species in the trade have also been introduced. This is the first study of aquarium trade imports to compare commercial invoices to government forms and provides a means to, routinely and in real time, examine the biodiversity of the trade in coral reef wildlife species

Individual Predisposition, Household Clustering and Risk Factors for Human Infection with Ascaris lumbricoides: New Epidemiological Insights

Numerous analyses have found that people infected with roundworm (Ascaris lumbricoides) are predisposed to harbor either many or few worms. Members of the same household also tend to harbor similar numbers of worms. These phenomena are called individual predisposition and household clustering respectively. In this article, we use Bayesian methods to fit a statistical model to worm count data collected from a cohort of participants at baseline and after two rounds of re-infection following curative treatment. We show that individual predisposition is extremely weak once the clustering effect of the household has been accounted for. This suggests that predisposition is of limited importance to the epidemiology of roundworm infection. Further, we show that over half of the variability in average worm counts among households is explained by household risk factors. This implies that exposures to infectious roundworm eggs shared by household members are important determinants of household clustering. We argue that these results support the hypothesis proposed in the literature that the household is a key focus of roundworm transmission

Chagas Disease Risk in Texas

Chagas disease is endemic in Texas and spread through triatomine insect vectors known as kissing bugs, assassin bugs, or cone–nosed bugs, which transmit the protozoan parasite, Trypanosoma cruzi. We examined the threat of Chagas disease due to the three most prevalent vector species and from human case occurrences and human population data at the county level. We modeled the distribution of each vector species using occurrence data from México and the United States and environmental variables. We then computed the ecological risk from the distribution models and combined it with disease incidence data to produce a composite risk map which was subsequently used to calculate the populations expected to be at risk for the disease. South Texas had the highest relative risk. We recommend mandatory reporting of Chagas disease in Texas, testing of blood donations in high risk counties, human and canine testing for Chagas disease antibodies in high risk counties, and that a joint initiative be developed between the United States and México to combat Chagas disease

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (&lt;50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

BackgroundThe safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.MethodsPANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.FindingsBetween Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.InterpretationMolnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community