Alumanyl Reduction, Reductive Coupling and C-H Isomerization of Organic Nitriles.

The behavior of the potassium alumanyl, [{SiNDipp}AlK]2 ({SiNDipp} = {CH2SiMe2N(Dipp)}2; Dipp = 2,6-i-Pr2C6H3), toward organic nitriles has been investigated. In common with earlier studies of the reactivity of charge neutral Al(I) species with multiply bonded small molecules, it is suggested that the initial step in all the reactions involves [2 + 1] cycloaddition and the generation of an [η2-C=N-Al] alumina azacyclopropane unit. In the cases of o- and m-tolyl-substituted aryl nitriles, this species is too kinetically labile to allow its isolation and undergoes C-C coupling via immediate Al-C/C≡N insertion to yield the alumina diazabutadiene derivatives. In contrast, the increased steric profile of alkyl nitriles imposes a marked influence on the nature of the products formed. Consistent with the proposed sequential pathway, reaction of [{SiNDipp}AlK]2 with t-BuCN provides an isolable alumina cyclopropane species that is kinetically resistant to onward reaction with a further nitrile equivalent. While reduction in the alkyl nitrile steric demands by use of i-PrCN again facilitates C-C bond formation, the crowding of the Al center by the resultant alumina-diazabutadienediide moiety appears to be beyond the limit of kinetic viability, resulting in an unusual 2-fold C-H to N-H isomerization from one of the C-iso-propyl substituents and the isolation of a 1-alumina-2,5-diazabutadiene structure.

Examining the relationship between different physical activities and health and well-being in middle-aged and older men: an isotemporal substitution analysis.

Background: Well-being declines during men's middle years, and while physical activity (PA) can have a positive influence, the type of PA that provides the greatest benefit is not clear. This cross-sectional study explored how participation in different types of PA is associated with the well-being and self-rated health of middle-aged and older men. Methods: A representative sample of South Australian adults completed a survey which assessed time spent in a variety of physical activities and self-rated health, life worth, life satisfaction and previous day happiness and anxiety. This study focused on a subsample of men≥35 years of age (n=1019). Partition and isotemporal substitution analyses were used to explore relationships between different types of PA and self-rated health and well-being outcomes. Results: Weekly PA was positively associated with all outcomes among middle-aged men (35-64 years), but only with self-rated health and life satisfaction in older men (65+ years). Substituting out 30 mins of team sport participation with cycling, fitness/gym-based activities or other recreational activities was associated with higher self-rated health in middle-aged men. In older men, substituting 30 mins of dance with most other types of PA was related with greater self-rated health and life worth. Conclusions: Total weekly PA was consistently related to the self-rated health and well-being of middle-aged men, but less so among older men. Despite some substitution effects for self-rated health, for the most part well-being was not influenced by activity substitution, particularly among middle-aged men.

Aligned Bioelectronic Polypyrrole/Collagen Constructs for Peripheral Nerve Interfacing.

Electrical stimulation has shown promise in clinical studies to treat nerve injuries. This work is aimed to create an aligned bioelectronic construct that can be used to bridge a nerve gap, directly interfacing with the damaged nerve tissue to provide growth support. The conductive three-dimensional bioelectronic scaffolds described herein are composite materials, comprised of conductive polypyrrole (PPy) nanoparticles embedded in an aligned collagen hydrogel. The bioelectronic constructs are seeded with dorsal root ganglion derived primary rat neurons and electrically stimulated in vitro. The PPy loaded constructs support a 1.7-fold increase in neurite length in comparison to control collagen constructs. Furthermore, upon electrical stimulation of the PPy-collagen construct, a 1.8-fold increase in neurite length is shown. This work illustrates the potential of bioelectronic constructs in neural tissue engineering and lays the groundwork for the development of novel bioelectronic materials for neural interfacing applications.

Stensen's Duct Dynamic Anatomy Assessed with Sialography.

Objectives: The presence of a catheter required for contrast infusion during sialography obscures imaging of the distal duct. Static imaging via cone beam computed tomography and magnetic resonance sialography fails to address changes that occur dynamically to the anatomy of the flexible salivary ductal system. We aim to identify dynamic changes to the parotid gland by introducing a novel approach to analyze the full extent of Stensen's duct based on dynamic infusion digital sialography. Methods: Retrospective chart review of a single-center consecutive series of 409 parotid sialograms performed between April 2008 and June 2023 permitted selection of a contemporary series including seven normal sialograms and seven sialograms with stricture(s). Dynamic (fluoroscopic) infusion (iopamidol/gadolinium) sialograms were assessed through blinded review by two radiologists employing the institution's picture archiving and communication (PACS) system (©2023 Koninklijke Philips N.V., Amsterdam, Netherlands). Measurements determined changes, in two dimensions, to the angle of the masseteric bend and duct length while the catheter was in place (repose), during catheter withdrawal (stretch), and during recoil after withdrawal. Differences in median lengths and angles of Stensen's duct between the three time points were compared using Wilcoxon matched-pairs signed rank and Mann-Whitney tests. Results: Fourteen patients [median age (IQR), 55 years (24.7); 10 women] were evaluated. The median angle of the masseteric bend was 117.7° in repose versus 155.4° during catheter withdrawal (P < .001, n = 14). The median distance measured from the Stensen's duct orifice to the first major ductal bifurcation was 81.5 mm (IQR = 12.3) in repose. The median percent increase in length from repose to stretch was 6.3% (P < .001, n = 14). Conclusions: Dynamic infusion digital sialography with fluoroscopic recording during catheter removal permits assessment of the distal duct unobstructed by the presence of a catheter. The technique also identifies the dynamic nature and varying length and angulation of Stensen's duct.

Establishing species boundaries in Bornean geckos.

Species delimitation using mitochondrial DNA (mtDNA) remains an important and accessible approach for discovering and delimiting species. However, delimiting species with a single locus (e.g. DNA barcoding) is biased towards overestimating species diversity. The highly diverse gecko genus Cyrtodactylus is one such group where delimitation using mtDNA remains the paradigm. In this study, we use genomic data to test putative species boundaries established using mtDNA within three recognized species of Cyrtodactylus on the island of Borneo. We predict that multi-locus genomic data will estimate fewer species than mtDNA, which could have important ramifications for the species diversity within the genus. We aim to (i) investigate the correspondence between species delimitations using mtDNA and genomic data, (ii) infer species trees for each target species, and (iii) quantify gene flow and identify migration patterns to assess population connectivity. We find that species diversity is overestimated and that species boundaries differ between mtDNA and nuclear data. This underscores the value of using genomic data to reassess mtDNA-based species delimitations for taxa lacking clear species boundaries. We expect the number of recognized species within Cyrtodactylus to continue increasing, but, when possible, genomic data should be included to inform more accurate species boundaries.

Impact of restricted family presence during the COVID-19 pandemic on critically ill patients, families, and critical care clinicians: a qualitative systematic review.

BACKGROUND: We aimed to synthesize the qualitative evidence on the impacts of COVID-19-related restricted family presence policies from the perspective of patients, families, and healthcare professionals from neonatal (NICU), pediatric (PICU), or adult ICUs. METHODS: We searched MEDLINE, EMBASE, Cochrane Databases of Reviews and Clinical Trials, CINAHL, Scopus, PsycINFO, and Web of Science. Two researchers independently reviewed titles/abstracts and full-text articles for inclusion. Thematic analysis was completed following appraising article quality and assessing confidence in the individual review findings using standardized tools. RESULTS: We synthesized 54 findings from 184 studies, revealing the impacts of these policies in children and adults on: (1) Family integrated care and patient and family-centered care (e.g., disruption to breastfeeding/kangaroo care, dehumanizing of patients); (2) Patients, families, and healthcare professionals (e.g., negative mental health consequences, moral distress); (3) Support systems (e.g., loss of support from friends/families); and (4) Relationships (e.g., loss of essential bonding with infant, struggle to develop trust). Strategies to mitigate these impacts are reported. CONCLUSION: This review highlights the multifaceted impacts of restricted visitation policies across distinct care settings and strategies to mitigate the harmful effects of these policies and guide the creation of compassionate family presence policies in future health crises. REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=290263 .

Optimising in-cell NMR acquisition for nucleic acids.

Understanding the structure and function of nucleic acids in their native environment is crucial to structural biology and one focus of in-cell NMR spectroscopy. Many challenges hamper in-cell NMR in human cell lines, e.g. sample decay through cell death and RNA degradation. The resulting low signal intensities and broad line widths limit the use of more complex NMR experiments, reducing the possible structural and dynamic information that can be extracted. Here, we optimize the detection of imino proton signals, indicators of base-pairing and therefore secondary structure, of a double-stranded DNA oligonucleotide in HeLa cells, using selective excitation. We demonstrate the reproducible quantification of in-cell selective longitudinal relaxation times (selT1), which are reduced compared to the in vitro environment, as a result of interactions with the complex cellular environment. By measuring the intracellular selT1, we optimize the existing proton pulse sequences, and shorten measurement time whilst enhancing the signal gained per unit of time. This exemplifies an advantage of selective excitation over conventional methods like jump-return water suppression for in-cell NMR. Furthermore, important experimental controls are discussed, including intracellular quantification, supernatant control measurements, as well as the processing of lowly concentrated in-cell NMR samples. We expect that robust and fast in-cell NMR experiments of nucleic acids will facilitate the study of structure and dynamics and reveal their functional correlation.

Poor Outcomes of Girdlestone Resection Arthroplasty in Injection Drug Users: A Retrospective Study.

This retrospective cohort study aims to investigate the clinical outcomes of Girdlestone resection arthroplasty (GRA) in injection drug users with septic hip arthritis. Patients who underwent primary GRA for septic hip arthritis secondary to injection drug use at two academic trauma centers from 2015 to 2023 were retrospectively reviewed. Patient demographics, surgical details, and follow-up outcomes, including patient-reported outcome measures, were collected and analyzed. The cohort included 15 patients, with a mean age of 44 ± 11 years and a mean follow-up period of 25 ± 20 months. Among the 15 patients, overall mortality was 27%, and only 4 patients underwent total hip arthroplasty (THA) following GRA. Infection resolution rates were significantly higher in patients who received an antibiotic spacer (75% vs. 0%, p = 0.048). GRA in injection drug users is associated with high mortality and low conversion rates to THA. The use of an antibiotic spacer during GRA significantly improves infection resolution rates. Larger studies are required to determine the optimal management strategies for this patient population.

A sucrose-binding protein and ß-conglycinins regulate soybean seed protein content and control multiple seed traits.

Expanded agriculture production is required to support the world's population but can impose substantial environmental and climate change costs, particularly with intensifying animal production and protein demand. Shifting from an animal- to a plant-based protein diet has numerous health benefits. Soybean (Glycine max (L.) Merr.) is a major source of protein for human food and animal feed; improved soybean protein content and amino acid composition could provide high-quality soymeal for animal feed, healthier human foods, and a reduced carbon footprint. Nonetheless, during the soybean genome evolution, a balance was established between the amount of seed protein, oil, and carbohydrate content, burdening the development of soybean cultivars with high proteins. We isolated two high-seed protein (HP) soybean mutants, HP1 and HP2, with improved seed amino acid composition and stachyose content, pointing to their involvement in controlling seed rebalancing phenomenon. HP1 encodes ß-conglycinin (GmCG-1) and HP2 encodes Sucrose Binding Protein (GmSBP-1), which are both highly expressed in soybean seeds. Mutations in GmSBP-1, GmCG-1, and the paralog GmCG-2 resulted in increased protein levels, confirming their role as general regulators of seed protein content, amino acid seed composition, and seed vigor. Biodiversity analysis of GmCG and GmSBP across 108 soybean accessions revealed haplotypes correlated with protein and seed carbohydrate content. Furthermore, our data revealed an unprecedented role of GmCG and GmSBP proteins in improving seed vigor, crude protein, and amino acid digestibility. Since GmSBP and GmCG are present in most seed plants analyzed, these genes could be targeted to improve multiple seed traits.

Considering collaborative incident management: A study of the COVID-19 response and initial recovery in a rural West Virginia community.

Hierarchical command-style structures are commonplace in the management of disasters, though researchers have begun to recommend the exploration of networked approaches to incident management. Furthermore, few studies are explicitly looking at the rural context of disaster management. This study seeks to contribute to both topics by examining the motivations for emergent collaboration in the direction of the response and initial recovery to the coronavirus disease 2019 pandemic in a rural West Virginia community. Between March 2020 and March 2022, the primary investigator moderated regular briefings of a community task force convened to coordinate the pandemic response and recovery. As regular operations concluded, members completed a survey, and 10 randomly selected members participated in semistructured interviews regarding their experiences in the task force. Survey responses suggest that common motivations for collaboration in nondisaster contexts (as they appear in the scholarly literature) and potential benefits of networked approaches highlighted in the incident management literature could also serve as motivators within the disaster context. Qualitative interview data extend that discussion and identify the need to gain clear information regarding the concerned authorities and specific local information to better inform the expenditure of limited resources as two additional motivators for collaboration.

Re-Purposing the Ordering of Routine Laboratory Tests in Hospitalized Medical Patients (RePORT): protocol for a multicenter stepped-wedge cluster randomised trial to evaluate the impact of a multicomponent intervention bundle to reduce laboratory test over-utilization.

BACKGROUND: Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada. METHODS: We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2-3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes. DISCUSSION: The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work. TRIAL REGISTRATION: This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic. CLINICALTRIALS: gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1.

Biomarkers of peanut allergy in children over time.

BACKGROUND: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. METHODS: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point. RESULTS: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time. CONCLUSIONS: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time.

Wild grass-derived alleles represent a genetic architecture for the resilience of modern common wheat to stresses.

This review explores the integration of wild grass-derived alleles into modern bread wheat breeding to tackle the challenges of climate change and increasing food demand. With a focus on synthetic hexaploid wheat, this review highlights the potential of genetic variability in wheat wild relatives, particularly Aegilops tauschii, for improving resilience to multifactorial stresses like drought, heat, and salinity. The evolutionary journey of wheat (Triticum spp.) from diploid to hexaploid species is examined, revealing significant genetic contributions from wild grasses. We also emphasize the importance of understanding incomplete lineage sorting in the genomic evolution of wheat. Grasping this information is crucial as it can guide breeders in selecting the appropriate alleles from the gene pool of wild relatives to incorporate into modern wheat varieties. This approach improves the precision of phylogenetic relationships and increases the overall effectiveness of breeding strategies. This review also addresses the challenges in utilizing the wheat wild genetic resources, such as the linkage drag and cross-compatibility issues. Finally, we culminate the review with future perspectives, advocating for a combined approach of high-throughput phenotyping tools and advanced genomic techniques to comprehensively understand the genetic and regulatory architectures of wheat under stress conditions, paving the way for more precise and efficient breeding strategies.

Asymmetric ion transport through "Janus" MoSSe sub-nanometer pores.

We conduct all-atom molecular dynamics simulations to systematically investigate the underlying mechanisms governing ion transport through a sub-nanometer pore decorated with negative charges in a "Janus" MoSSe membrane. The charge imbalance between S and Se atoms on each side of the membrane induces different types of ion adsorption processes depending on the pore inner charge configuration, and the polarity of external biases, which leads to asymmetry in ionic I-V characteristics. Statistical analysis of the total translocation times including adsorption-desorption processes, and ion dwell times indicates that potassium ions predominantly remain adsorbed during their interaction with the membrane before undertaking a quick translocation through the pore. High applied biases suppress cation adsorption, which results in fast translocation with the current flow boosted by negative inner charges around the pore. We also show that in a membrane consisting of several "Janus" layers, the applied bias necessary to overcome the sub-nm pore barrier increases with the number of layers, providing control over the ionic current.

Well-being approaches targeted to improve child and youth health post-COVID-19 pandemic: a scoping review.

BACKGROUND: Our previous work synthesized published studies on well-being interventions during COVID-19. As we move into a post-COVID-19 pandemic period there is a need to comprehensively review published strategies, approaches, and interventions to improve child and youth well-being beyond deleterious impacts experienced during COVID-19. METHODS: Seven databases were searched from inception to January 2023. Studies were included if they: (1) presented original data on an approach (i.e., approach applied) or (2) provided recommendations to inform development of a future approach (i.e., approach suggested), (3) targeted to mitigate negative impacts of COVID-19 on child and youth (≤18 year) well-being, and (4) published on or after December 2019. RESULTS: 39 studies (n = 4/39, 10.3% randomized controlled trials) from 2021 to 2023 were included. Twenty-two studies applied an approach (n = 22/39, 56.4%) whereas seventeen studies (n = 17/39, 43.6%) suggested an approach; youth aged 13-18 year (n = 27/39, 69.2%) were most frequently studied. Approach applied records most frequently adopted an experimental design (n = 11/22, 50.0%), whereas approach suggested records most frequently adopted a cross-sectional design (n = 13/22, 59.1%). The most frequently reported outcomes related to good health and optimum nutrition (n = 28/39, 71.8%), followed by connectedness (n = 22/39, 56.4%), learning, competence, education, skills, and employability (n = 18/39, 46.1%), and agency and resilience (n = 16/39, 41.0%). CONCLUSIONS: The rapid onset and unpredictability of COVID-19 precluded meaningful engagement of children and youth in strategy development despite widespread recognition that early engagement can enhance usefulness and acceptability of interventions. Published or recommended strategies were most frequently targeted to improve connectedness, belonging, and socialization among children and youth.

Dried Plasma for Major Trauma: Past, Present, and Future.

Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well.

The borylamino-diborata-allyl anion.

Reactions of ß-diketiminato alkaline earth alkyldiboranate derivatives [(BDI)Ae{pinBB(R)pin}] (BDI = HC{(Me)CNDipp}2; Dipp = 2,6-i-Pr2C6H3; Ae = Mg, R = n-Bu or Ae = Ca, R = n-hexyl) with t-BuNC provide access to the respective group 2 derivatives of unprecedented diborata-allyl, {(pinB)2CNBpin(t-Bu)}-, anions. Although the necessary mode of B-C bond cleavage implicated in these transformations could not be elucidated, further studies of the reactivity of magnesium triboranates toward isonitriles delivered a more general and rational synthetic access to analogous anionic moieties. Extending this latter reactivity to a less symmetric triboranate variant also provided an isomeric Mg-C-bonded dibora-alkyl species and sufficient experimental insight to prompt theoretical evaluation of this reactivity. DFT calculations, thus, support a reaction pathway predicated on initial RNC attack at a peripheral boron centre and the intermediacy of such dibora-alkyl intermediates.

Clovis organizational dynamics at a Late Glacial campsite in the central Great Lakes: Belson site excavations 2020-2021.

The Belson site is located on an outwash plain draining the Early Algonquin stage of the central Great Lakes (coinciding with the Older Dryas stadial period around 14,000 Cal B.P) southwest across Lower Michigan into the Ohio tributaries. By 13,000 Cal B.P the St. Joseph River had incised multiple channels into this plain. On a terrace just north of a now-abandoned channel, a detailed surface study by Talbot from 2005-2018 showed several flake clusters largely of Attica chert, procured about 235 km southwest of Belson. A study of the surface sample was published by the authors in 2021 and indicated that the points were made with the Clovis technological pattern. Excavations in 2020-21 revealed hundreds of buried flakes and multiple tools in the lower, less-disturbed terrace sediment. Plotting of this material indicates successive occupations below the ploughed deposit and covering more than 30 m2. The buried assemblages are similar to the published surface assemblage with the addition of more small scrapers and manufacturing debris. Several of the buried tools have traces of proteins from a range of mammals, suggesting a broad-spectrum subsistence strategy. The documentation of a succession of little disturbed deposits with precisely recorded micro-debris will allow for testing of models describing settlement choice and developing dynamics of internal site organization. Initial analysis of recovered data provides support for an 'outcrop centered' model where high-quality chert outcrops serve as central places on the landscape. Samples of sediment and charcoal for identification and dating await study.

Hypotonic, gel-forming delivery system for vaginal drug administration.

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT.

Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention.

BACKGROUND: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption. METHODS: Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months. RESULTS: We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 µg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 µg/l. Adverse events were uncommon, and the majority were related to the food challenge. CONCLUSIONS: Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).