Chitosan-based multifunctional oxygenating antibiotic hydrogel dressings for managing chronic infection in diabetic wounds.

Current treatment strategies for infection of chronic wounds often result in compromised healing and necrosis due to antibiotic toxicity, and underlying biomarkers affected by treatments are not fully known. Here, a multifunctional dressing was developed leveraging the unique wound-healing properties of chitosan, a natural polysaccharide known for its numerous benefits in wound care. The dressing consists of an oxygenating perfluorocarbon functionalized methacrylic chitosan (MACF) hydrogel incorporated with antibacterial polyhexamethylene biguanide (PHMB). A non-healing diabetic infected wound model with emerging metabolomics tools was used to explore the anti-infective and wound healing properties of the resultant multifunctional dressing. Direct bacterial bioburden assessment demonstrated superior antibacterial properties of hydrogels over a commercial dressing. However, wound tissue quality analyses confirmed that sustained PHMB for 21 days resulted in tissue necrosis and disturbed healing. Therefore, a follow-up comparative study investigated the best treatment course for antiseptic application ranging from 7 to 21 days, followed by the oxygenating chitosan-based MACF treatment for the remainder of the 21 days. Bacterial counts, tissue assessments, and lipidomics studies showed that 14 days of application of MACF-PHMB dressings followed by 7 days of MACF dressings provides a promising treatment for managing infected non-healing diabetic skin ulcers.

Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use in patients with persistent abdominal pain, but their specific effect on this symptom has not been assessed systematically. METHODS: We searched the literature through December 16, 2023, for randomized controlled trials (RCTs) assessing efficacy of BGBTs for adults with IBS, compared with each other or a control intervention. Trials provided an assessment of abdominal pain resolution or improvement at treatment completion. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of abdominal pain not improving with 95% confidence intervals (CIs), ranking therapies according to the P score. RESULTS: We identified 42 eligible randomized controlled trials comprising 5220 participants. After treatment completion, the BGBTs with the largest numbers of trials and patients recruited demonstrating efficacy for abdominal pain, specifically, included self-guided/minimal contact cognitive behavioral therapy (CBT) (RR, 0.71; 95% CI, 0.54-0.95; P score, 0.58), face-to-face multicomponent behavioral therapy (RR, 0.72; 95% CI, 0.54-0.97; P score, 0.56), and face-to-face gut-directed hypnotherapy (RR, 0.77; 95% CI, 0.61-0.96; P score, 0.49). Among trials recruiting only patients with refractory global IBS symptoms, group CBT was more efficacious than routine care for abdominal pain, but no other significant differences were detected. No trials were low risk of bias across all domains, and there was evidence of funnel plot asymmetry. CONCLUSIONS: Several BGBTs, including self-guided/minimal contact CBT, face-to-face multicomponent behavioral therapy, and face-to-face gut-directed hypnotherapy may be efficacious for abdominal pain in IBS, although none was superior to another.

Changes in holopelagic Sargassum spp. biomass composition across an unusual year.

The year 2021 marked a decade of holopelagic sargassum (morphotypes Sargassum natans I and VIII, and Sargassum fluitans III) stranding on the Caribbean and West African coasts. Beaching of millions of tons of sargassum negatively impacts coastal ecosystems, economies, and human health. Additionally, the La Soufrière volcano erupted in St. Vincent in April 2021, at the start of the sargassum season. We investigated potential monthly variations in morphotype abundance and biomass composition of sargassum harvested in Jamaica and assessed the influence of processing methods (shade-drying vs. frozen samples) and of volcanic ash exposure on biochemical and elemental components. S. fluitans III was the most abundant morphotype across the year. Limited monthly variations were observed for key brown algal components (phlorotannins, fucoxanthin, and alginate). Shade-drying did not significantly alter the contents of proteins but affected levels of phlorotannins, fucoxanthin, mannitol, and alginate. Simulation of sargassum and volcanic ash drift combined with age statistics suggested that sargassum potentially shared the surface layer with ash for ~50 d, approximately 100 d before stranding in Jamaica. Integrated elemental analysis of volcanic ash, ambient seawater, and sargassum biomass showed that algae harvested from August had accumulated P, Al, Fe, Mn, Zn, and Ni, probably from the ash, and contained less As. This ash fingerprint confirmed the geographical origin and drift timescale of sargassum. Since environmental conditions and processing methods influence biomass composition, efforts should continue to improve understanding, forecasting, monitoring, and valorizing sargassum, particularly as strandings of sargassum show no sign of abating.

FicD regulates adaptation to the unfolded protein response in the murine liver.

The unfolded protein response (UPR) is a cellular stress response that is activated when misfolded proteins accumulate in the endoplasmic reticulum (ER). Regulation of the UPR response must be adapted to the needs of the cell as prolonged UPR responses can result in disrupted cellular function and tissue damage. Previously, we discovered that the enzyme FicD (also known as Fic or HYPE) through its AMPylation and deAMPylation activity can modulate the UPR response via post-translational modification of BiP. FicD AMPylates BiP during homeostasis and deAMPylates BiP during stress. We hypothesized that FicD regulation of the UPR will play a role in mitigating the deleterious effects of UPR activation in tissues with frequent physiological stress. Here, we explore the role of FicD in the murine liver. As seen in our pancreatic studies, livers lacking FicD exhibit enhanced UPR signaling in response to short term physiologic fasting and feeding stress. However, in contrast to studies on the pancreas, livers, as a more regenerative tissue, remained remarkably resilient in the absence of FicD. The livers of FicD-/- did not show marked changes in UPR signaling or damage after either chronic high fat diet (HFD) feeding or acute pathological UPR induction. Intriguingly, FicD-/- mice showed changes in UPR induction and weight loss patterns following repeated pathological UPR induction. These findings indicate that FicD regulates UPR responses during mild physiological stress and in adaptation to repeated stresses, but there are tissue specific differences in the requirement for FicD regulation.

Can genetic rescue help save Arabia's last big cat?

Genetic diversity underpins evolutionary potential that is essential for the long-term viability of wildlife populations. Captive populations harbor genetic diversity potentially lost in the wild, which could be valuable for release programs and genetic rescue. The Critically Endangered Arabian leopard (Panthera pardus nimr) has disappeared from most of its former range across the Arabian Peninsula, with fewer than 120 individuals left in the wild, and an additional 64 leopards in captivity. We (i) examine genetic diversity in the wild and captive populations to identify global patterns of genetic diversity and structure; (ii) estimate the size of the remaining leopard population across the Dhofar mountains of Oman using spatially explicit capture-recapture models on DNA and camera trap data, and (iii) explore the impact of genetic rescue using three complementary computer modeling approaches. We estimated a population size of 51 (95% CI 32-79) in the Dhofar mountains and found that 8 out of 25 microsatellite alleles present in eight loci in captive leopards were undetected in the wild. This includes two alleles present only in captive founders known to have been wild-sourced from Yemen, which suggests that this captive population represents an important source for genetic rescue. We then assessed the benefits of reintroducing novel genetic diversity into the wild population as well as the risks of elevating the genetic load through the release of captive-bred individuals. Simulations indicate that genetic rescue can improve the long-term viability of the wild population by reducing its genetic load and realized load. The model also suggests that the genetic load has been partly purged in the captive population, potentially making it a valuable source population for genetic rescue. However, the greater loss of its genetic diversity could exacerbate genomic erosion of the wild population during a rescue program, and these risks and benefits should be carefully evaluated. An important next step in the recovery of the Arabian leopard is to empirically validate these conclusions, implement and monitor a genomics-informed management plan, and optimize a strategy for genetic rescue as a tool to recover Arabia's last big cat.

Backbone-functionalised ruthenium diphosphine complexes for catalytic upgrading of ethanol and methanol to iso-butanol.

Efficient catalysts for Guerbet-type ethanol/methanol upgrading to iso-butanol have been developed via Michael addition of a variety of amines to ruthenium-coordinated dppen (1,1-bis(diphenylphosphino)ethylene). All catalysts produce over 50% iso-butanol yield with >90% selectivity in 2 h with catalyst 1 showing the best activity (74% yield after this time). The selectivity and turnover number approach 100% and 1000 respectively using catalyst 6. The presence of uncoordinated functionalised donor groups in these complexes results in a more stable catalyst compared to unfunctionalised analogues.

Disrupting the Hofmeister bias in salt liquid-liquid extraction with an arylethynyl bisurea anion receptor.

Host-mediated liquid-liquid extraction is a convenient method for the separation of inorganic salts. However, selective extraction of an anion, regardless of its hydrophilicity or lipophilicity as qualitatively described by its place in the Hofmeister series, remains challenging. Herein we report the complete disruption of the Hofmeister-based ordering of anions in host-mediated extraction by a rigidified tweezer-type receptor possessing remarkably strong anion-binding affinity under the conditions examined. Experiments introduce a convenient new method for determination of anion binding using phosphorus inductively coupled plasma mass spectrometry (ICP-MS) to measure extraction of tetra-n-butylphosphonium (TBP+) salts from water into nitrobenzene, specifically examining the disrupting effect of the added arylethynyl bisurea anion receptor. In the absence of the receptor, the salt partitioning follows the expected Hofmeister-type ordering favoring the larger, less hydrated anions; the analysis yields the value -24 kJ mol-1 for the standard Gibbs energy of partitioning of TBP+ cation from water into nitrobenzene at 25 °C. Selectivity is markedly changed by the addition of receptor to the nitrobenzene and is concentration dependent, giving rise to three selectivity regimes. We then used SXLSQI liquid-liquid equilibrium analysis software developed at Oak Ridge National Laboratory to fit host-mediated extraction equilibria for TBP+ salts of Cl-, Br-, I-, and NO3- to the distribution data. While the reverse-Hofmeister 1 : 1 binding of the anions by the receptor effectively cancels the Hofmeister selectivity of the TBPX partitioning into nitrobenzene, formation of unexpected 2 : 1 receptor : anion complexes favoring Cl- and Br- dominates the selectivity at elevated receptor concentrations, producing the unusual order Br- > Cl- > NO3- > I- in anion distribution wherein a middle member of the series is selected and the most lipophilic anion is disfavored. Density functional theory calculations confirmed the likelihood of forming 2 : 1 complexes, where Cl- and Br- are encapsulated by two receptors adopting energetically competitive single or double helix structures. The calculations explain the rare non-Hofmeister preference for Br-. This example shows that anion receptors can be used to control the selectivity and efficiency of salt extraction regardless of the position of the anion in the Hofmeister series.

FicD regulates adaptation to the unfolded protein response in the murine liver.

The unfolded protein response (UPR) is a cellular stress response that is activated when misfolded proteins accumulate in the endoplasmic reticulum (ER). The UPR elicits a signaling cascade that results in an upregulation of protein folding machinery and cell survival signals. However, prolonged UPR responses can result in elevated cellular inflammation, damage, and even cell death. Thus, regulation of the UPR response must be tuned to the needs of the cell, sensitive enough to respond to the stress but pliable enough to be stopped after the crisis has passed. Previously, we discovered that the bi-functional enzyme FicD can modulate the UPR response via post-translational modification of BiP. FicD AMPylates BiP during homeostasis and deAMPylates BiP during stress. We found this activity is important for the physiological regulation of the exocrine pancreas. Here, we explore the role of FicD in the murine liver. Like our previous studies, livers lacking FicD exhibit enhanced UPR signaling in response to short term physiologic fasting and feeding stress. However, the livers of FicD -/- did not show marked changes in UPR signaling or damage after either chronic high fat diet (HFD) feeding or acute pathological UPR induction. Intriguingly, FicD -/- mice showed changes in UPR induction and weight loss patterns following repeated pathological UPR induction. These findings show that FicD regulates UPR responses during mild physiological stress and may play a role in maintaining resiliency of tissue through adaptation to repeated ER stress.

Talking in primary care (TIP): protocol for a cluster-randomised controlled trial in UK primary care to assess clinical and cost-effectiveness of communication skills e-learning for practitioners on patients' musculoskeletal pain and enablement.

INTRODUCTION: Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain. METHODS AND ANALYSIS: A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews. ETHICS APPROVAL AND DISSEMINATION: Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country. TRIAL REGISTRATION NUMBER: ISRCTN18010240.

A combined strategies intervention on the World Health Organization prescribing indicators: A quasi-randomised trial.

BACKGROUND: Irrational medicine use is a global problem that may potentiate antimicrobial resistance. AIM: This study aims to assess prescribing practices and the effect of a prescription audit and feedback coupled with small-group education intervention on prescribing indicators. SETTING: The study was conducted in public-sector healthcare facilities in Eswatini. METHODS: A cluster quasi-randomised controlled study was conducted from 2016 to 2019 using the World Health Organization/ International Network for Rational Use of Drugs (WHO/INRUD) prescribing indicators at baseline, post-intervention and post-follow-up. A 6-month unblinded intervention was tested in 32 healthcare facilities, randomly allocated to intervention (16) and control (16) arms. Prescribing practices were assessed post-intervention, and 6 months after the intervention, through an audit of 100 randomly selected prescriptions from each facility. Comparisons of WHO or INRUD prescribing indicators were conducted using the intention-to-treat analysis at the two times. RESULTS: At baseline, in both arms, rational prescribing standards were met by the number of medicines per prescription and the use of injections. Antibiotic use was above 50% in both arms. After adjustment for baseline antibiotics use, region and level of care, there were no significant differences in all prescribing indicators between the two arms, post-intervention and at 6 months follow-up. CONCLUSION: In a lower middle-income setting with a high prevalence of irrational prescribing practices, a prescription audit, feedback and small-group education intervention had no benefits in improving rational prescribing.Contribution: Multifaceted strategies, strengthening of pharmacy and therapeutics committees, and holistic monitoring of medicine use are recommended to promote rational medicine use.

Lactation curves of Montbéliarde-sired and Viking Red-sired crossbred cows and their Holstein herdmates in commercial dairies.

Lactation curves were estimated for Montbéliarde (MO) × Holstein (HO) and Viking Red (VR) × HO 2-breed crossbred cows and for MO × VR/HO and VR × MO/HO 3-breed crossbred cows and their HO herdmates from test-day observations in 7 high-performance herds that participated in a designed study. Cows calved from 2010 to 2017. Test-day observations from milk recording were used to fit the lactation curves of cows in their first 3 lactations. Lactations of cows were required to have at least 250 DIM and to have at least 6 test days ≤265 DIM. Lactation curves from random regression (RR) were compared for 305-d production (kg), peak production (kg), peak day of production, and production from 4 to 103 DIM (kg), from 104 to 205 DIM (kg), and from 206 to 305 DIM (kg) for milk, fat, and protein. Also, the persistency of production was compared. First-lactation versus second- and third-lactation cows were analyzed separately for both the 2-breed and 3-breed crossbred cows and their respective HO herdmates. Legendre polynomial RR had the best goodness of fit for the lactation curves compared with Ali-Schaeffer and Wilmink RR from the test-day observations of milk, fat, and protein production. For fluid milk production of first-lactation cows, the MO × HO 2-breed crossbreds were not different from their HO herdmates for any of the lactation-curve characteristics, except persistency. However, the VR × HO 2-breed crossbreds had less fluid milk production compared with their HO herdmates. For first lactation, the MO × HO 2-breed crossbreds had more persistency of milk, fat, and protein production compared with their HO herdmates. The first-lactation MO × VR/HO 3-breed crossbreds had more persistency of fluid milk production compared with their HO herdmates. For second and third lactations, both the MO × HO and the VR × HO 2-breed crossbreds had higher fat production compared with their HO herdmates. Furthermore, the MO × HO 2-breed crossbreds had more protein production (kg) in all 3 periods of lactation compared with their HO herdmates. Crossbred cows may have advantages over HO cows for persistency of production in high-performance herds.

Clinging fauna associated with nearshore pelagic sargassum rafts in the Eastern Caribbean: Implications for coastal in-water harvesting.

Tropical Atlantic blooms of pelagic Sargassum species are associated with severe inundation events along the coasts of Caribbean and West African nations that cause extensive ecological and socioeconomic harm. The use of in-water harvesting as a management strategy avoids the plethora of challenges associated with shoreline inundations. Moreover, with a growing interest in the valorisation of this raw material, in-water harvesting provides the best opportunity to collect substantial amounts of 'fresh' sargassum that can be used in a variety of applications. However, in-water harvesting of sargassum will remove organisms associated with the floating habitat, resulting in loss of biodiversity, thus creating a potential management dilemma. To address this management concern, we assessed the clinging fauna associated with sargassum rafts at various distances from shore. From a total of 119 dipnet samples of sargassum, we recorded 18 taxa, across 6 phyla (Arthropoda, Mollusca, Chordata, Platyhelminthes, Nemathelminthes, Annelida) with the phylum Arthropoda being the most speciose (n = 10). Our multivariate and model selection analyses support that distance from shore and season are the most important drivers of variability in community composition and that season is the most important driver of individual abundance and number of taxa across samples. Overall, rafts within 0-3000 m of the shoreline of Barbados harbored low biodiversity and were dominated by small invertebrates (mean size: 5.5 mm) of no commercial value. Results suggest that biodiversity trade-offs associated with in-water sargassum harvesting in coastal areas are likely to be negligible.

Microbial products linked to steatohepatitis are reduced by deletion of nuclear hormone receptor SHP in mice.

Deletion of the nuclear hormone receptor small heterodimer partner (Shp) ameliorates the development of obesity and nonalcoholic steatohepatitis (NASH) in mice. Liver-specific SHP plays a significant role in this amelioration. The gut microbiota has been associated with these metabolic disorders, and the interplay between bile acids (BAs) and gut microbiota contributes to various metabolic disorders. Since hepatic SHP is recognized as a critical regulator in BA synthesis, we assessed the involvement of gut microbiota in the antiobesity and anti-NASH phenotype of Shp-/- mice. Shp deletion significantly altered the levels of a few conjugated BAs. Sequencing the 16S rRNA gene in fecal samples collected from separately housed mice revealed apparent dysbiosis in Shp-/- mice. Cohousing Shp-/- mice with WT mice during a Western diet regimen impaired their metabolic improvement and effectively disrupted their distinctive microbiome structure, which became indistinguishable from that of WT mice. While the Western diet challenge significantly increased lipopolysaccharide and phenylacetic acid (PAA) levels in the blood of WT mice, their levels were not increased in Shp-/- mice. PAA was strongly associated with hepatic peroxisome proliferator-activated receptor gamma isoform 2 (Pparg2) activation in mice, which may represent the basis of the molecular mechanism underlying the association of gut bacteria and hepatic steatosis. Shp deletion reshapes the gut microbiota possibly by altering BAs. While lipopolysaccharide and PAA are the major driving forces derived from gut microbiota for NASH development, Shp deletion decreases these signaling molecules via dysbiosis, thereby partially protecting mice from diet-induced metabolic disorders.

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. METHODS: This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. FINDINGS: Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. INTERPRETATION: To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

Benchmarking the placement of hydrosulfide in the Hofmeister series using a bambus[6]uril-based ChemFET sensor.

Hydrosulfide (HS-) is the conjugate base of gasotransmitter hydrogen sulfide (H2S) and is a physiologically-relevant small molecule of great interest in the anion sensing community. However, selective sensing and molecular recognition of HS- in water remains difficult because, in addition to the diffuse charge and high solvation energy of anions, HS- is highly nucleophilic and readily oxidizes into other reactive sulfur species. Moreover, the direct placement of HS- in the Hofmeister series remains unclear. Supramolecular host-guest interactions provide a promising platform on which to recognize and bind hydrosulfide, and characterizing the placement of HS- in the Hofmeister series would facilitate the future design of selective receptors for this challenging anion. Few examples of supramolecular HS- binding have been reported, but the Sindelar group reported HS- binding in water using bambus[6]uril macrocycles in 2018. We used this HS- binding platform as a starting point to develop a chemically-sensitive field effect transistor (ChemFET) to facilitate assigning HS- to a specific place in the Hofmeister series. Specifically, we prepared dodeca-n-butyl bambus[6]uril and incorporated it into a ChemFET as the HS- receptor motif. The resultant device provided an amperometric response to HS-, and we used this device to measure the response of other anions, including SO42-, F-, Cl-, Br-, NO3-, ClO4-, and I-. Using this response data, we were able to experimentally determine that HS- lies between Cl- and Br- in the Hofmeister series, which matches recent theoretical computational work that predicted a similar placement. Taken together, these results highlight the potential of using molecular recognition coupled with ChemFET architectures to develop new approaches for direct and reversible HS- detection and measurement in water and further advance our understanding of different recognition approaches for this challenging anion.

An analysis of arsenic concentrations associated with sargassum influx events in Barbados.

Tropical Atlantic blooms of pelagic Sargassum spp. present major socioeconomic and ecological challenges for Caribbean and West African nations. Valorisation of sargassum provides an opportunity to ameliorate some of the damage to national economies; however, the active uptake of arsenic by pelagic sargassum creates significant barriers to its use. When defining valorisation pathways, it is important to understand arsenic speciation in pelagic sargassum, given the different levels of toxicity associated with different arsenic species. In this study, we assess the temporal variability of total arsenic and inorganic arsenic in pelagic sargassum arriving in Barbados; and test whether arsenic concentrations are linked to oceanic sub-origins. Results indicate that inorganic arsenic, the most toxic form, represents a consistent and substantial percentage of the total arsenic present in pelagic sargassum, and that variability in arsenic concentration does not appear to be driven by sample months, years or oceanic sub-origins/transport pathways.

Seasonal variation in morphotype composition of pelagic Sargassum influx events is linked to oceanic origin.

The recent proliferation of pelagic Sargassum spp. in the Tropical Atlantic causes major ecological and socioeconomic impacts to the wider Caribbean when it washes ashore, with regional fisheries and tourism industries particularly affected. The Caribbean influxes have been tracked to a new bloom region known as the North Equatorial Recirculation Region (NERR) encompassing the area between the South Equatorial Current and the North Equatorial Counter Current and extending from Africa to South America. The vast biomass of Sargassum presents serious problems when it washes ashore but also represents significant commercial opportunities, especially with biofuel and fertilizer. The floating Sargassum mats are themselves diverse ecosystems that vary both in their biodiversity and biochemical attributes. Two major species (Sargassum fluitans and S. natans) have been identified as well as several distinguishable morphotypes of each. Oceanic mixing tends to blend the morphotypes together making it difficult to determine if there are regions of the NERR that favour bloom and growth of the distinct types. In this study, we quantify the species and morphotype composition of Sargassum strandings in Barbados and test if this is related to separate oceanic origins and routes travelled using a backtracking algorithm based on ocean drifter data. We found significant seasonal variation in the relative abundance of three morphotypes and this could be traced to two distinct easterly sub-origins and/or transport pathways; one area around 15° N that travels directly E-W across the Atlantic, and another area generally south of 10° N that takes a more meandering route coming close the coast of South America. These findings contribute towards our understanding of why the Tropical Atlantic bloom is presently occurring as well as towards addressing valorisation constraints surrounding variation in the supply of the three commonly occurring morphotypes.

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules.

The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99mTc, and the therapeutic radionuclide, 188Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph2PCH2CH2P(CH2CH2-Glc)2 (L, where Glc = a glucose moiety) using the readily accessible Ph2PCH2CH2PH2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either 99mTc(V) or 188Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of cis- and trans-[M(O)2L2]+ (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[99mTc(O)2L2]+ and trans-[99mTc(O)2L2]+ exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99mTc SPECT imaging and 188Re systemic radiotherapy.

Defining Pediatric Chronic Critical Illness: A Scoping Review.

OBJECTIVES: Children with chronic critical illness (CCI) are hypothesized to be a high-risk patient population with persistent multiple organ dysfunction and functional morbidities resulting in recurrent or prolonged critical care; however, it is unclear how CCI should be defined. The aim of this scoping review was to evaluate the existing literature for case definitions of pediatric CCI and case definitions of prolonged PICU admission and to explore the methodologies used to derive these definitions. DATA SOURCES: Four electronic databases (Ovid Medline, Embase, CINAHL, and Web of Science) from inception to March 3, 2021. STUDY SELECTION: We included studies that provided a specific case definition for CCI or prolonged PICU admission. Crowdsourcing was used to screen citations independently and in duplicate. A machine-learning algorithm was developed and validated using 6,284 citations assessed in duplicate by trained crowd reviewers. A hybrid of crowdsourcing and machine-learning methods was used to complete the remaining citation screening. DATA EXTRACTION: We extracted details of case definitions, study demographics, participant characteristics, and outcomes assessed. DATA SYNTHESIS: Sixty-seven studies were included. Twelve studies (18%) provided a definition for CCI that included concepts of PICU length of stay (n = 12), medical complexity or chronic conditions (n = 9), recurrent admissions (n = 9), technology dependence (n = 5), and uncertain prognosis (n = 1). Definitions were commonly referenced from another source (n = 6) or opinion-based (n = 5). The remaining 55 studies (82%) provided a definition for prolonged PICU admission, most frequently greater than or equal to 14 (n = 11) or greater than or equal to 28 days (n = 10). Most of these definitions were derived by investigator opinion (n = 24) or statistical method (n = 18). CONCLUSIONS: Pediatric CCI has been variably defined with regard to the concepts of patient complexity and chronicity of critical illness. A consensus definition is needed to advance this emerging and important area of pediatric critical care research.