Pro- and anti-inflammatory cytokines mediate the progression of severe anemia in malaria-infected children: A prospective study.

BACKGROUND: Severe Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti-inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria-infected children in Ghana. METHODS: This case-control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12-144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: Malaria-infected children had higher tumor necrosis factor alpha (TNF-α) (p < .001), interferon-gamma (IFN-É£) (p < .001), interleukin (IL)-1ß (p < .001), IL-6 (p < .001), granulocyte macrophage-colony stimulating factor (GM-CSF) (p < .001), and IL-10 (p < .001) levels than controls. Participants with high parasitemia had raised TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but reduced IL-3 (p < .001) and TGF-ß (p < .001) than those with low parasitemia. Severe malarial anemic children had elevated TNF-α (p < .001), IFN-É£ (p < .001), IL-1ß (p < .001), IL-6 (p < .001), GM-CSF (p < .001), and IL-10 (p < .001), but lower IL-3 (p < .001) and TGF-ß (p < .001) than those with uncomplicated malaria. CONCLUSION: Parasite density was the principal predictor of the cytokine levels, as parasitemia positively associated with IL-10, GM-CSF, IL-6, IL-1ß, IFN-É£, and TNF-α, but negatively associated with IL-3 and TGF-ß. Malaria is associated with enhanced secretion of pro- and anti-inflammatory cytokines in Ghanaian children. Inflammatory cytokines may be involved in the development of severe malarial anemia in children. However, IL-3 and TGF-ß may offer protection against severe malarial anemia.

Judges' attitudes and experiences related to a trauma-informed approach: An exploratory study.

OBJECTIVE: Understanding judges' views is crucial to the successful adoption of a trauma-informed (TI) approach in the U.S. court system, yet little is known on this topic. We explored judges' attitudes of and experiences with TI practice to help fill this gap. METHOD: We surveyed 91 North Carolina district court judges, assessing their attitudes related to TI practice, use of trauma-informed practices (TIPs), previous trauma education, and support for different justice goals. We conducted independent-samples t tests and Poisson regression analyses to compare attitudes, use of TIPs, and education experiences between judges working in juvenile justice and those not in juvenile justice; descriptive statistics to examine rates of engagement with different TIPs; and bivariate correlation analyses to assess associations between TI practice outcomes and justice goals. RESULTS: Analyses revealed more favorable attitudes toward a TI approach and greater engagement with trauma education among judges working in juvenile versus adult courts; TIPs with the lowest levels of engagement related to policies and procedures; and strong positive correlations between favorable TI practice attitudes and support for rehabilitation and restoration. CONCLUSION: Findings highlight areas for growth in the movement to create more TI courts, such as strengthening support for TI practice in the adult criminal system and implementing TIPs related to policies, procedures, and outcomes, not just communication. Findings also support the connection between a TI approach and less punitive justice practices, signaling the potential role that TI judicial practice can play in shifting our legal system toward more transformative forms of justice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Machine learning to attribute the source of Campylobacter infections in the United States: A retrospective analysis of national surveillance data.

OBJECTIVES: Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern, and there is an urgent need to quantify the main routes to human infection. METHODS: During routine US national surveillance (2009-2019), 8856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs. RESULTS: Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens. CONCLUSIONS: National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US. DATA AVAILABILITY: All sequence reads were uploaded and shared on NCBI's Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli).

Towards quantifying plasmid similarity.

Plasmids are extrachromosomal replicons which can quickly spread resistance and virulence genes between clinical pathogens. From the tens of thousands of currently available plasmid sequences we know that overall plasmid diversity is structured, with related plasmids sharing a largely conserved 'backbone' of genes while being able to carry very different genetic cargo. Moreover, plasmid genomes can be structurally plastic and undergo frequent rearrangements. So, how can we quantify plasmid similarity? Answering this question requires practical efforts to sample natural variation as well as theoretical considerations of what defines a group of related plasmids. Here we consider the challenges of analysing and rationalising the current plasmid data deluge to define appropriate similarity thresholds.

Management of Dorsal Bunion in Nonambulatory Adolescents with Cerebral Palsy: A Retrospective Cohort Study.

BACKGROUND: A dorsal bunion may occur in nonambulatory adolescents with cerebral palsy (CP) and a Gross Motor Function Classification System (GMFCS) level of IV or V. The deformity can cause pain, skin breakdown, and difficulty wearing shoes and braces. A consensus on the biomechanics and surgical management of dorsal bunions in persons with severe CP has not been established. METHODS: This retrospective cohort study included 23 nonambulatory adolescents with CP, GMFCS level IV or V, and symptomatic dorsal bunions requiring surgery. The median age at surgery was 17 years, and the median follow-up was 56 months. Reconstructive surgery included the excision of a 2 to 3-cm segment of the tibialis anterior tendon to correct the elevation of the first metatarsal. The fixed deformity of the first metatarsophalangeal joint was managed with use of corrective arthrodesis and dorsal plate fixation. Clinical and radiographic outcomes were assessed preoperatively and postoperatively at the transition to adult services. RESULTS: There were significant improvements in the clinical and radiographic outcome measures (p < 0.001). Pain was relieved, and there were no further episodes of skin breakdown. The elevation of the first metatarsal was corrected from a mean of 3° of dorsiflexion to a mean of 19° of plantar flexion. The deformity of the first metatarsophalangeal joint was corrected from a mean of 55° of plantar flexion to a mean of 21° of dorsiflexion. Six patients had complications, all of which were grade I or II according to the modified Clavien-Dindo system. CONCLUSIONS: The surgical reconstruction of a dorsal bunion via soft-tissue rebalancing of the first ray and corrective arthrodesis of the first metatarsophalangeal joint resulted in favorable medium-term clinical and radiographic outcomes in nonambulatory adolescents with CP. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Proximity to humans is associated with antimicrobial-resistant enteric pathogens in wild bird microbiomes.

Humans are radically altering global ecology, and one of the most apparent human-induced effects is urbanization, where high-density human habitats disrupt long-established ecotones. Changes to these transitional areas between organisms, especially enhanced contact among humans and wild animals, provide new opportunities for the spread of zoonotic pathogens. This poses a serious threat to global public health, but little is known about how habitat disruption impacts cross-species pathogen spread. Here, we investigated variation in the zoonotic enteric pathogen Campylobacter jejuni. The ubiquity of C. jejuni in wild bird gut microbiomes makes it an ideal organism for understanding how host behavior and ecology influence pathogen transition and spread. We analyzed 700 C. jejuni isolate genomes from 30 bird species in eight countries using a scalable generalized linear model approach. Comparing multiple behavioral and ecological traits showed that proximity to human habitation promotes lineage diversity and is associated with antimicrobial-resistant (AMR) strains in natural populations. Specifically, wild birds from urban areas harbored up to three times more C. jejuni genotypes and AMR genes. This study provides novel methodology and much-needed quantitative evidence linking urbanization to gene pool spread and zoonoses.

The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

Global Variation in Escherichia coli mcr-1 Genes and Plasmids from Animal and Human Genomes Following Colistin Usage Restrictions in Livestock.

Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.

Can Large Language Models (LLMs) Predict the Appropriate Treatment of Acute Hip Fractures in Older Adults? Comparing Appropriate Use Criteria With Recommendations From ChatGPT.

BACKGROUND: Acute hip fractures are a public health problem affecting primarily older adults. Chat Generative Pretrained Transformer may be useful in providing appropriate clinical recommendations for beneficial treatment. OBJECTIVE: To evaluate the accuracy of Chat Generative Pretrained Transformer (ChatGPT)-4.0 by comparing its appropriateness scores for acute hip fractures with the American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria given 30 patient scenarios. "Appropriateness" indicates the unexpected health benefits of treatment exceed the expected negative consequences by a wide margin. METHODS: Using the AAOS Appropriate Use Criteria as the benchmark, numerical scores from 1 to 9 assessed appropriateness. For each patient scenario, ChatGPT-4.0 was asked to assign an appropriate score for six treatments to manage acute hip fractures. RESULTS: Thirty patient scenarios were evaluated for 180 paired scores. Comparing ChatGPT-4.0 with AAOS scores, there was a positive correlation for multiple cannulated screw fixation, total hip arthroplasty, hemiarthroplasty, and long cephalomedullary nails. Statistically significant differences were observed only between scores for long cephalomedullary nails. CONCLUSION: ChatGPT-4.0 scores were not concordant with AAOS scores, overestimating the appropriateness of total hip arthroplasty, hemiarthroplasty, and long cephalomedullary nails, and underestimating the other three. ChatGPT-4.0 was inadequate in selecting an appropriate treatment deemed acceptable, most reasonable, and most likely to improve patient outcomes.

Comparison of the Clinical Manifestations of Acute Coronary Syndrome Between Diabetic and Non-diabetic Patients: A Systematic Review and Meta-Analysis.

The presentation of acute coronary syndrome (ACS) in patients with type 2 diabetes mellitus (T2DM) may differ from that of non-diabetic patients, potentially leading to delayed diagnosis and treatment. This meta-analysis aimed to compare the clinical presentation of ACS between diabetic and non-diabetic patients. A systematic search of PubMed, Excerpta Medica database (EMBASE), and Web of Science databases was conducted for observational studies published from January 2010 onwards. Studies comparing ACS symptoms between diabetic and non-diabetic patients were included. The odds ratio (OR) with 95% confidence intervals (CI) was calculated using a random-effects model. Eight studies with a total of 29,503 patients (23.03% diabetic) were included. Diabetic patients were significantly less likely to present with chest pain compared to non-diabetic patients (OR: 0.43, 95% CI: 0.30 to 0.63, p<0.001). Anxiety (OR: 2.20, 95% CI: 1.17-4.14), shortness of breath (OR: 1.49, 95% CI: 1.11-2.01), and neck pain (OR: 1.62, 95% CI: 1.03-2.54) were significantly more common in diabetic patients. Sweating/cold sweat was less common in diabetics (OR: 0.60, 95% CI: 0.34-1.07), though not statistically significant. Other symptoms showed minimal differences between groups. High heterogeneity was observed across studies for most symptoms. This meta-analysis demonstrates that diabetic patients with ACS are less likely to experience typical chest pain and more likely to present with atypical symptoms such as anxiety, shortness of breath, and neck pain. These findings emphasize the need for healthcare providers to maintain high vigilance for atypical ACS presentations in diabetic patients. Tailored diagnostic approaches, modified triage protocols, and enhanced patient education are crucial to improving the timely diagnosis and treatment of ACS in this high-risk population.

Bibliometric Patent Review of Minimally Invasive Spine Surgery.

STUDY DESIGN: This study analyzes patents associated with minimally invasive spine surgery (MISS) found on the Lens open online platform. OBJECTIVE: The goal of this research was to provide an overview of the most referenced patents in the field of MISS and to uncover patterns in the evolution and categorization of these patents. SUMMARY OF BACKGROUND DATA: MISS has rapidly progressed, with a core focus on minimizing surgical damage, preserving the natural anatomy, and enabling swift recovery, all while achieving outcomes that rival traditional open surgery. While prior studies have primarily concentrated on MISS outcomes, the analysis of MISS patents has been limited. METHODS: To conduct this study, we used the Lens platform to search for patents that included the terms "minimally invasive" and "spine" in their titles, abstracts, or claims. We then categorized these patents and identified the top 100 with the most forward citations. We further classified these patents into 4 categories: Spinal Stabilization Systems, Joint Implants or Procedures, Screw Delivery System or Method, and Access and Surgical Pathway Formation. RESULTS: Five hundred two MISS patents were identified initially, and 276 were retained following a screening process. Among the top 100 patents, the majority had active legal status. The largest category within the top 100 patents was Access and Surgical Pathway Formation, closely followed by Spinal Stabilization Systems and Joint Implants or Procedures. The smallest category was Screw Delivery System or Method. Notably, the majority of the top 100 patents had priority years falling between 2000 and 2009, indicating a moderate positive correlation between patent rank and priority year. CONCLUSIONS: Thus far, patents related to Access and Surgical Pathway Formation have laid the foundation for subsequent innovations in Spinal Stabilization Systems and Screw Technology. This study serves as a valuable resource for guiding future innovations in this rapidly evolving field.

A hybrid approach to sample size re-estimation in cluster randomized trials with continuous outcomes.

This study presents a hybrid (Bayesian-frequentist) approach to sample size re-estimation (SSRE) for cluster randomised trials with continuous outcome data, allowing for uncertainty in the intra-cluster correlation (ICC). In the hybrid framework, pre-trial knowledge about the ICC is captured by placing a Truncated Normal prior on it, which is then updated at an interim analysis using the study data, and used in expected power control. On average, both the hybrid and frequentist approaches mitigate against the implications of misspecifying the ICC at the trial's design stage. In addition, both frameworks lead to SSRE designs with approximate control of the type I error-rate at the desired level. It is clearly demonstrated how the hybrid approach is able to reduce the high variability in the re-estimated sample size observed within the frequentist framework, based on the informativeness of the prior. However, misspecification of a highly informative prior can cause significant power loss. In conclusion, a hybrid approach could offer advantages to cluster randomised trials using SSRE. Specifically, when there is available data or expert opinion to help guide the choice of prior for the ICC, the hybrid approach can reduce the variance of the re-estimated required sample size compared to a frequentist approach. As SSRE is unlikely to be employed when there is substantial amounts of such data available (ie, when a constructed prior is highly informative), the greatest utility of a hybrid approach to SSRE likely lies when there is low-quality evidence available to guide the choice of prior.

Predicting population-level impacts of projected climate heating on a temperate freshwater fish.

Climate heating has the potential to drive changes in ecosystems at multiple levels of biological organization. Temperature directly affects the inherent physiology of plants and animals, resulting in changes in rates of photosynthesis and respiration, and trophic interactions. Predicting temperature-dependent changes in physiological and trophic processes, however, is challenging because environmental conditions and ecosystem structure vary across biogeographical regions of the globe. To realistically predict the effects of projected climate heating on wildlife populations, mechanistic tools are required to incorporate the inherent physiological effects of temperature changes, as well as the associated effects on food availability within and across comparable ecosystems. Here we applied an agent-based bioenergetics model to explore the combined effects of projected temperature increases for 2100 (1.4, 2.7, and 4.4°C), and associated changes in prey availability, on three-spined stickleback (Gasterosteus aculeatus) populations representing latitudes 50, 55, and 60°N. Our results showed a decline in population density after a simulated 1.4°C temperature increase at 50°N. In all other modeled scenarios there was an increase (inflation) in population density and biomass (per unit area) with climate heating, and this inflation increased with increasing latitude. We conclude that agent-based bioenergetics models are valuable tools in discerning the impacts of climate change on wild fish populations, which play important roles in aquatic food webs.

Explainable Machine Learning Approach to Prediction of Prolonged Intesive Care Unit Stay in Adult Spinal Deformity Patients: Machine Learning Outperforms Logistic Regression.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Prolonged ICU stay is a driver of higher costs and inferior outcomes in Adult Spinal Deformity (ASD) patients. Machine learning (ML) models have recently been seen as a viable method of predicting pre-operative risk but are often 'black boxes' that do not fully explain the decision-making process. This study aims to demonstrate ML can achieve similar or greater predictive power as traditional statistical methods and follows traditional clinical decision-making processes. METHODS: Five ML models (Decision Tree, Random Forest, Support Vector Classifier, GradBoost, and a CNN) were trained on data collected from a large urban academic center to predict whether prolonged ICU stay would be required post-operatively. 535 patients who underwent posterior fusion or combined fusion for treatment of ASD were included in each model with a 70-20-10 train-test-validation split. Further analysis was performed using Shapley Additive Explanation (SHAP) values to provide insight into each model's decision-making process. RESULTS: The model's Area Under the Receiver Operating Curve (AUROC) ranged from 0.67 to 0.83. The Random Forest model achieved the highest score. The model considered length of surgery, complications, and estimated blood loss to be the greatest predictors of prolonged ICU stay based on SHAP values. CONCLUSIONS: We developed a ML model that was able to predict whether prolonged ICU stay was required in ASD patients. Further SHAP analysis demonstrated our model aligned with traditional clinical thinking. Thus, ML models have strong potential to assist with risk stratification and more effective and cost-efficient care.

Water-powered, electronics-free dressings that electrically stimulate wounds for rapid wound closure.

Chronic wounds affect ~2% of the U.S. population and increase risks of amputation and mortality. Unfortunately, treatments for such wounds are often expensive, complex, and only moderately effective. Electrotherapy represents a cost-effective treatment; however, its reliance on bulky equipment limits its clinical use. Here, we introduce water-powered, electronics-free dressings (WPEDs) that offer a unique solution to this issue. The WPED performs even under harsh conditions-situations wherein many present treatments fail. It uses a flexible, biocompatible magnesium-silver/silver chloride battery and a pair of stimulation electrodes; upon the addition of water, the battery creates a radial electric field. Experiments in diabetic mice confirm the WPED's ability to accelerate wound closure and promote healing by increasing epidermal thickness, modulating inflammation, and promoting angiogenesis. Across preclinical wound models, the WPED-treated group heals faster than the control with wound closure rates comparable to treatments requiring expensive biologics and/or complex electronics. The results demonstrate the WPED's potential as an effective and more practical wound treatment dressing.

Molecular Detection of Tick-Borne Pathogens in Kumasi: With a First Report of Zoonotic Pathogens in Abattoir Workers.

Tick-borne pathogens continue to infect humans and animals worldwide. By adapting to the movement of livestock, ticks facilitate the spread of these infectious pathogens. Humans in close contact with animals that could be amplifying hosts are especially at risk of being infected with tick-borne pathogens. This study involved the collection of dry blood spots (DBSs) to determine tick-borne pathogens occurring in slaughtered livestock and abattoir workers in Kumasi. This study employed the use of conventional PCR, RT-PCR, and Sanger sequencing to detect and identify the tick-borne pathogens. The resulting data was analysed using Stata version 13. A total of 175 DBSs were collected from goats (76), cattle (54), and sheep (45) in the Kumasi abattoir (130, 74.29%) and Akwatia Line slaughter slab (45, 25.71%). The pathogens identified were mostly bacterial including Anaplasma capra (9.71%), Anaplasma phagocytophilum (1.14%), and Rickettsia aeschlimannii (0.57.%). The only parasite identified was Theileria ovis (9.14%). A significant association was seen between A. capra (p < 0.001) infection and female sheep sampled from the Akwatia Line slaughter slab. Again, there was a significant association between T. ovis (p < 0.001) infections and female sheep from the Kumasi abattoir. From the human DBS (63) screened, the pathogens identified were all bacterial including Coxiella burnetii (1.89%), Rickettsia africae (1.89%), and R. aeschlimannii (1.89%). This study reports the first detection of R. aeschlimannii in livestock as well as the occurrence of the above-mentioned pathogens in humans in Ghana. Animals can serve as amplifying hosts for infectious pathogens; hence, there is an increased risk of infections among the abattoir workers. Continuous surveillance effort is essential, and abattoir workers need to protect themselves from tick bites and infectious tick-borne pathogens.

Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19.

Soluble angiotensin-converting enzyme 2 (ACE2) can act as a decoy molecule that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by blocking spike (S) proteins on virions from binding ACE2 on host cells. Based on structural insights of ACE2 and S proteins, we designed a "muco-trapping" ACE2-Fc conjugate, termed ACE2-(G4S)6-Fc, comprised of the extracellular segment of ACE2 (lacking the C-terminal collectrin domain) that is linked to mucin-binding IgG1-Fc via an extended glycine-serine flexible linker. ACE2-(G4S)6-Fc exhibits substantially greater binding affinity and neutralization potency than conventional full length ACE2-Fc decoys or similar truncated ACE2-Fc decoys without flexible linkers, possessing picomolar binding affinity and strong neutralization potency against pseudovirus and live virus. ACE2-(G4S)6-Fc effectively trapped fluorescent SARS-CoV-2 virus like particles in fresh human airway mucus and was stably nebulized using a commercial vibrating mesh nebulizer. Intranasal dosing of ACE2-(G4S)6-Fc in hamsters as late as 2 days postinfection provided a 10-fold reduction in viral load in the nasal turbinate tissues by Day 4. These results strongly support further development of ACE2-(G4S)6-Fc as an inhaled immunotherapy for COVID-19, as well as other emerging viruses that bind ACE2 for cellular entry.

Supportive care interventions in metastatic bone disease: scoping review.

BACKGROUND: Patients with secondary metastatic involvement of the musculoskeletal system due to primary cancers are a rapidly growing population with significant risks for health-related end-of-life morbidities. In particular, bone metastases or metastatic bone disease (MBD) imparts significant adversity to remaining quality of life. No rigorous review of clinical trials on the use of supportive care interventions for MBD has been conducted. The objective of this review was to examine the characteristics of supportive care interventions for MBD and critically appraise study designs, key findings, and quality of evidence of the research. METHODS: We searched for published clinical trials, systematic reviews and meta-analyses in PubMED, CINAHL and Google Scholar for articles published between September 2017 and September 2022. Some examples of Medical Subject Headings terms were: 'secondary neoplasm', 'metastatic bone disease', 'palliative care' and 'supportive care intervention'. Quality of published evidence was evaluated based on treatment types and study design. RESULTS: After reviewing 572 publications, 13 articles were included in the final review and evaluation including seven clinical trials, two trial protocols and four systematic reviews. Feasible interventions included enhanced palliative care consultation, palliative radiotherapy and alternative medicines. Interventions addressed primary endpoints of fatigue (N=4, 31%), pain (N=3, 23%) or cancer-related symptoms (N=3, 23%) with patient-reported outcome instruments. No interventions reported on fracture complications or endpoints, specifically. The quality of most studies was moderate to strong. CONCLUSION: Supportive care interventions for MBD are feasible and the impact is measurable via patient-reported outcome measures. While the evidence for interventions was moderate to strong, there are very few specific controlled trials for skeletal-related events and impacts of social determinants of health. Further clinical trials are needed to define supportive care interventions for MBD that demonstrate reduced risk of fracture and that mitigate the reduced quality of life when negative musculoskeletal outcomes arise.

Medical abortion in Ghana: A non-randomized, non-inferiority study of access through pharmacies compared with clinics.

OBJECTIVES: To compare self-reported clinical outcomes following medical abortion with mifepristone and misoprostol sourced from either a pharmacy or health clinic. STUDY DESIGN: We conducted a prospective, non-randomized, non-inferiority cohort study across four regions in Ghana, from high-volume pharmacies and health clinics. Participants seeking medical abortion (less than nine weeks' gestation) who met usual medical abortion eligibility criteria were recruited. Data collection included baseline surveys, follow-up phone interviews, and self-reported assessments of medical abortion outcomes. The study aimed to enroll 2000 medical abortion users (1000 from each source). RESULTS: Complete outcome data was available and analyzed from 1958 participants (of 2208 enrolled), with the adjusted risk difference of need for additional treatment to complete the abortion indicating non-inferiority of the pharmacy group compared to the clinic group [-2.3% (95% CI -5.3% to 0.7%)]. Both groups reported low rates of additional treatment (4.9%) and adhered similarly to the abortion regimen. Secondary outcomes showed no significant differences, with moderate acceptability in both groups (65.4% pharmacy, 52.3% facility). Adverse outcomes were rare: one ectopic pregnancy, one blood transfusion and no deaths or other major complications were reported. CONCLUSIONS: Accessing medical abortion pills directly from pharmacies without prior consultation from a provider demonstrated non-inferior self-reported clinical outcomes compared to seeking care from health clinics. The findings align with the growing global evidence supporting the safety and effectiveness of medical abortion self-care. IMPLICATIONS: This study contributes data which support future registration of over-the-counter use of medical abortion drugs up to nine weeks' gestation. Such measures could expand options for safe abortion care, especially in regions where unsafe abortion poses a substantial maternal health risk. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03727308).

Modelling the potential impact of global hepatitis B vaccination on the burden of chronic hepatitis B in the United States.

About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non-US-born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B-related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B-related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings.