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As carbon-based nanomaterials have such remarkable physical, chemical, and electrical capabilities, they have become a major focus of materials science study. A thorough examination of several carbon nanomaterial varieties, such as carbon nanotubes, graphene, fullerenes, and carbon nanodiamonds, is given in this review work. These materials all have distinctive qualities that qualify them for particular uses. This work starts by examining the synthesis processes of these nanomaterials, outlining the ways by which they are made and the variables affecting their ultimate characteristics. The specific features of each kind of carbon nanomaterial will then be briefly discussed in this study, along with their size, structure, and special physical and chemical properties. These materials have a wide range of possible uses in several fields. They are employed in the electronics industry to fabricate sensors, high-speed transistors, and other devices. Their high surface area and electrical conductivity make them useful in energy storage devices like supercapacitors and batteries. They are applied to environmental remediation and water purification in environmental science. They are employed in biomedicine for biosensing, bioimaging, and medication delivery. Notwithstanding the encouraging uses, the large-scale synthesis and functionalization of carbon nanomaterials present several difficulties. This review discusses the importance of carbon nanomaterials by studying their multifaceted properties and potential applications in industries. The novelty of this work lies in its detailed examination of the degradation and toxicity of these materials, which is essential for their safe integration into various technological and biomedical applications. By thoroughly analysing recent experimental results, this review aims to bridge the gap between fundamental research and practical applications.

Abstract Background US nursing homes were ground zero for COVID-19 and nursing home leaders faced multiple challenges to keep residents and staff safe. Understanding the leader’s role and their use of external resources to rapidly respond to the pandemic is important to better prepare for the next infectious disease outbreak emergency. The purpose of this study is to describe Missouri nursing home leaders’ use of external resources to manage challenges encountered during the pandemic. Methods This qualitative descriptive study uses data from semi-structured interviews conducted with leaders from 24 Midwestern nursing homes between March 2022 and March 2023. Interviews were transcribed verbatim and analyzed using Dedoose software. Directed content analysis, guided by Donabedian’s Structure, Process, Outcome framework, was used for analysis. Interviews were conducted as part of a larger mixed-methods study focused on developing knowledge and recommendations to improve US nursing homes’ capacity to respond to infectious disease outbreaks. Results Forty-three interviews were conducted across the 24 homes. Participants included administrators (n = 24), nurse leaders (n = 19), and infection preventionists (n = 16). Six sub-categories of external resources/support were used by leaders to manage challenges during the pandemic:1) corporate support and communications, 2) statewide resources, 3) community-based resources, 4) health care coalitions focused on emergency response planning, 5) existing affiliations with local organizations i.e., hospitals, and 6) community members and families. Corporate support was a primary resource; however, it was limited to chain-based homes. Leaders from standalone homes seemed most reliant on statewide agencies, existing affiliations, and other community-based resources due to their lack of corporate connections. Health care coalitions were few, but when available, helped nursing homes prepare for the pandemic onset. Family and community members were vital despite being off-site from nursing homes at the pandemic onset. Conclusion Leaders played a pivotal role in accessing and using external resources to manage challenges during the pandemic. Statewide and community-based agencies and existing affiliations were particularly critical for standalone homes who otherwise had little to no means of support. Federal, state and local agencies must consider opportunities to build multi-agency regional collaborations, local health care coalitions and community-based partnerships that include nursing homes as member. Finally, community members and family were important in providing support, thus closing visitation is a double-edged sword that needs careful, future consideration.

Abstract Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients of BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving from anteromedial to posterolateral BF, we observe reduced tethering between structural and functional connectivity gradients, with the lowest tethering in the nucleus basalis of Meynert. In the neocortex, this gradient is expressed by progressively reduced tethering from unimodal sensory to transmodal cortex, with the lowest tethering in the midcingulo-insular network, and is also spatially correlated with the molecular concentration of VAChT, measured by [18F]fluoroethoxy-benzovesamicol (FEOBV) PET. In mice, viral tracing of BF cholinergic projections and [18F]FEOBV PET confirm a gradient of axonal arborization. Altogether, our findings reveal that BF cholinergic neurons vary in their branch complexity, with certain subpopulations exhibiting greater modularity and others greater diffusivity in the functional integration with their cortical targets.

Abstract We developed and evaluated an electronic health record (EHR)-based model for suicide risk specific to an American Indian patient population. Using EHR data for all patients over 18 with a visit between 1/1/2017 and 10/2/2021, we developed a model for the risk of a suicide attempt or death in the 90 days following a visit. Features included demographics, medications, diagnoses, and scores from relevant screening tools. We compared the predictive performance of logistic regression and random forest models against existing suicide screening, which was augmented to include the history of previous attempts or ideation. During the study, 16,835 patients had 331,588 visits, with 490 attempts and 37 deaths by suicide. The logistic regression and random forest models (area under the ROC (AUROC) 0.83 [0.80–0.86]; both models) performed better than enhanced screening (AUROC 0.64 [0.61–0.67]). These results suggest that an EHR-based suicide risk model can add value to existing practices at Indian Health Service clinics.

Abstract Few insect-specific alphaviruses (ISA) have been discovered, with even fewer culturable to facilitate full characterisation. Here, we report the recovery of an infectious clone of Yada Yada virus (YYV)—a virus previously only detected by metagenomic sequencing of mosquito homogenates. Using the infectious clone, we confirmed the inability of YYV to replicate in vertebrate cells in vitro, with replication limited to only Aedes mosquito-derived cell lines. We further produced and characterised the first monoclonal antibodies (mAbs) to ISAs. Through successful replacement of the structural proteins of YYV with those of other ISAs, Eilat virus, Agua Salud (ASALV), Taï Forest (TALV) and Mwinilunga alphaviruses (MWAV), we established that a replication block for in vitro culture of TALV and MWAV in mosquito cells does not exist at virus entry. Unexpectedly, ASALV structural proteins were recognised by cross-reactive mAbs made to chikungunya (CHIKV) and Ross River viruses (RRV), suggesting a potential antigenic link between ASALV and pathogenic alphaviruses. The YYV genetic backbone was also investigated to generate chimeras displaying the structural proteins of various pathogenic vertebrate-infecting alphaviruses including CHIKV, RRV, Barmah Forest, Sindbis and Mayaro viruses. These chimeras retained the antigenic properties of the parental viruses and did not replicate in vertebrate cells, demonstrating the potential of the YYV platform for vaccine and diagnostic antigen production.

Objectives: This study evaluated the role of Upc2 in the development of azole resistance in Candida albicans isolates from Lebanese hospitalized patients and determined a correlation between resistance and virulence. Methods: The UPC2 gene which codes for an ergosterol biosynthesis regulator was sequenced and analysed in two azole-resistant and one azole-susceptible C. albicans isolates. An amino acid substitution screening was carried out on Upc2 with a focus on its ligand binding domain (LBD) known to interact with ergosterol. Then, Upc2 protein secondary structure prediction and homology modelling were conducted, followed by total plasma membrane ergosterol and cell wall chitin quantifications. For virulence, mouse models of systemic infection were generated and an agar adhesion and invasion test was performed. Results: Azole-resistant isolates harboured novel amino acid substitutions in the LBD of Upc2 and changes in protein secondary structures were observed. In addition, these isolates exhibited a significant increase in plasma membrane ergosterol content. Resistance and virulence were inversely correlated while increased cell wall chitin concentration does not seem to be linked to resistance since even though we observed an increase in chitin concentration, it was not statistically significant. Conclusions: The azole-resistant C. albicans isolates harboured novel amino acid substitutions in the LBD of Upc2 which are speculated to induce an increase in plasma membrane ergosterol content, preventing the binding of azoles to their target, resulting in resistance.

Caprine livestock are significant reservoirs of the Mycobacterium tuberculosis complex (MTBC), contributing to tuberculosis (TB) transmission among animals and humans. The P22 protein immunocomplex (P22PI), derived from bovine tuberculin, shows immunostimulating capacity and is used for TB diagnosis. This study assessed the immunogenicity and protective efficacy of P22PI in two groups of goats: 24 naïve goats (12 immunised, 12 controls) from a TB-free herd, and 24 infected goats (12 immunised, 12 controls), referred to as pre-infected animals, from a M. bovis-infected herd. Both were exposed for 5 months to M. bovis-naturally infected goats. Reactors to single and comparative intradermal tuberculin (SIT and SCIT, respectively) tests and interferon-gamma release assay (IGRA) significantly increased (p

Abstract Background This paper documents changes in the prevalence and intensity of soil-transmitted helminth (STH) infections in the Geshiyaro project in the Wolaita zone of Southern Ethiopia. Methods The Geshiyaro project comprises three intervention arms. Arm 1 is subdivided into the Arm 1 pilot (one district) and Arm 1 (four other districts), both receiving integrated community-wide mass drug administration MDA (cMDA) with intensive water, sanitation, and hygiene (WaSH) interventions. Arm 2 involves 18 districts with cMDA interventions plus the existing government-led One WaSH program, while Arm 3 serves as a control with school-based MDA (sMDA) interventions plus the existing government-led One WaSH program in three districts. The study is designed as a cohort investigation over time, with the establishment of longitudinal sentinel sites where infection levels are assessed annually. A total of 45 longitudinal parasitological surveillance sentinel sites are being used across all three intervention arms to monitor STH prevalence and intensity of infection. From each of the 45 sentinel sites, 150 individuals were randomly selected, stratified by age and gender. The t-test and analysis of variance (ANOVA) were employed to compare infection prevalence and intensity across the three study arms over time. Results The prevalence of STH decreased significantly from 34.5% (30.6%, 38.5%) in 2019 to 10.6% (8.3%, 13.4%) in 2022/2023 (df = 1, P

Abstract In 2022, a genotype IV (GIV) strain of Japanese encephalitis virus (JEV) caused an unprecedented and widespread outbreak of disease in pigs and humans in Australia. As no veterinary vaccines against JEV are approved in Australia and all current approved human and veterinary vaccines are derived from genotype (G) III JEV strains, we used the recently described insect-specific Binjari virus (BinJV) chimeric flavivirus vaccine technology to produce a JEV GIV vaccine candidate. Herein we describe the production of a chimeric virus displaying the structural prM and E proteins of a JEV GIV isolate obtained from a stillborn piglet (JEVNSW/22) in the genomic backbone of BinJV (BinJ/JEVNSW/22-prME). BinJ/JEVNSW/22-prME was shown to be antigenically indistinguishable from the JEVNSW/22 parental virus by KD analysis and a panel of JEV-reactive monoclonal antibodies in ELISA. BinJ/JEVNSW/22-prME replicated efficiently in C6/36 cells, reaching titres of >107 infectious units/mL - an important attribute for vaccine manufacture. As expected, BinJ/JEVNSW/22-prME failed to replicate in a variety of vertebrate cells lines. When used to immunise mice, the vaccine induced a potent virus neutralising response against JEVNSW/22 and to GII and GIII JEV strains. The BinJ/JEVNSW/22-prME vaccine provided complete protection against lethal challenge with JEVNSW/22, whilst also providing partial protection against viraemia and disease for the related Murray Valley encephalitis virus. Our results demonstrate that BinJ/JEVNSW/22-prME is a promising vaccine candidate against JEV.

Abstract Background The SARS-CoV-2 pandemic led to unprecedented testing demands, causing major testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. However, such traditional pooled testing was used in practice only when positivity rates were below 2%. Methods Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel. Results P-BEST is clinically validated using 3636 side-by-side tests and is able to correctly detect all positive samples and accurately estimate their Ct value. Following regulatory approval by the Israeli Ministry of Health, P-BEST was used in 2021 to clinically test 837,138 samples using 270,095 PCR tests - a 3.1fold reduction in the number of tests. This period includes the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available. Conclusions Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks.

Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and proimmune properties; however, their use has not been rigorously studied in human TBI populations. A single-center, retrospective, descriptive observational study was conducted at the LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ? 8) who remained in the ICU for ?2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared with those who received standard, polymeric EN with regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.

ABSTRACT: Objectives: This study aimed to identify the resistance mechanisms to micafungin and fluconazole in a clinical isolate of Candida glabrata. Methods: The isolate was whole-genome sequenced to identify amino acid changes in key proteins involved in antifungal resistance, and the isolate was further characterised by pathogenicity-related phenotypic assays that supported the sequencing results. Results: Amino acid substitutions were detected in 8 of 17 protein candidates. Many of these substitutions were novel, including in CHS3, CHS3B, and KRE5, which are involved in the development of micafungin resistance. Regarding fluconazole resistance, overexpression of efflux pumps was observed. Our isolate did not exhibit an increased virulence potential compared with the control strain; however, a significant increase in chitin content and potential to resist the cell surface disruptant sodium dodecyl sulphate was observed. Conclusions: This clinical Candida glabrata isolate experienced a change in cell wall architecture, which correlates with the development of micafungin resistance.

Over the past few decades, nanotechnology has gained momentum because of its potential to create a safer and healthier living environment using eco-friendly approaches. This study describes a safer, more dependable, and ecologically friendly technique of biologically synthesizing Cu/Fe/Ag trimetallic nanoparticles (NPs) using an aqueous leaf extract of Catharanthus roseus as the reducing and stabilizing agent. The synthesized trimetallic NPs were characterized by scanning electron microscope, Fourier transform infrared, dynamic light scattering, and ultraviolet–visible analysis and were evaluated for their potential applications, which included antioxidant properties and catalytic dye degradation. The result suggests that the antioxidant properties of Cu/Fe/Ag NPs are more significant than those of ascorbic acid, a known antioxidant, at lower doses (10 µg·ml−1) while a higher dose of 1,000 µg·ml−1 gives a 69.81% scavenging activity. The impact of Cu/Fe/Ag trimetallic NPs on the catalytic degradation of hazardous dyes such as phenol red (PR) and eosin yellow (EY) was also studied in this work. For PR and EY, the corresponding percentages of degradation were 76% and 48.6%, respectively.

During a survey of plant-parasitic nematodes in Costa Rica, Quinisulcius capitatus was isolated and identified for the first time in three locations: Barva and Santa Bárbara in the Heredia province, and Vázquez de Coronado in the San José province. The nematodes were extracted from soil samples by the sugar solution centrifugation-flotation method, and the specimens described and characterized based on integrative taxonomy. The adult nematodes of Q. capitatus are in accordance with the type population, but displayed slight morphometric variations in relation to those originally described: body length of 649.5-875.7 vs. 630-850, style length of 13.7-17 vs. 16-18 and percentage of vulva of 52.7-59.9 vs. 51-58. The D2-D3 expansion segments of the 28S rDNA from the recovered populations were sequenced and used in the phylogenetic analysis. The Costa Rican populations showed a high similarity and formed a separate clade with the Pakistani and Ethiopian populations deposited in the GenBank® database. This study expands the species geographic distribution and provides the first morphometric and molecular characterization of Q. capitatus from Costa Rica.

Titanium carbide (Ti3C2Tx) MXene has attracted significant attention due to its exceptional properties and versatile solution processibility. However, MXene dispersions are prone to various degradation processes, leading to the formation of byproducts that negatively affect its morphological, electrical, and mechanical properties. Through the years, several methods have been developed to mitigate MXene degradation; however, divergent viewpoints on the understanding of degradation mechanisms are prevalent, hindering the development of versatile strategies in producing environmentally stable MXene dispersions. This review provides a chronological analysis of the research efforts aimed at unraveling the underlying mechanisms of MXene degradation and highlights strategies for circumventing this process. This review discusses apparent inconsistencies in experimental findings and theoretical models. These discrepancies prompt further investigation for a clearer understanding of the degradation process in MXene. This narrative allows readers to follow the evolution of dominant theories and disputes and to ultimately stimulate further investigation, aiming for a better understanding of this process. It is anticipated that identifying the fundamental factors affecting the oxidation of MXene dispersions will enable their full‐scale processing into higher‐order structures and practical devices with greater longevity and long‐term performance.

Novel concepts for efficient compact spectroscopy are extensively researched due to their fundamental applications in prominent fields such as chemistry, biology, and physics. Here, with an unprecedented spectral-azimuthal resolution, such a concept is introduced and exemplified in the mid-infrared, in which its advantages are paramount and have yet to be established industrially. The concept is based on the design and instrumentation of optical absorption spectral tuning (or sensitivity) to the relative azimuthal component of light impinging on specifically designed metamaterials (MMs). The inversely-designed MMs offer perfect photo-absorption inside λ0/200 ultra-thin layer of lead telluride. Two small-footprint system designs are proposed to instrument the spectral-azimuth-angle tuning for spectrometry. The first is based on a single or few spinning MM layout elements, and the second, to avoid spinning, utilizes a fixed focal-plane-array approach. The latter exploits the inherent variations in the local azimuthal-incidence angle. While low absorption is the Achilles heel of conventional mid-infrared photodetector spectrometers, the optimized MMs, besides their unique spectral-azimuth-angle tuning functionality, provide giant absorption enhancement, facilitating higher resolution and even smaller in-plane form factor. The highlighted concept opens an additional dimension to encode-decode spectral information, yielding profound advantages over conventional designs, such as those based on diffraction gratings.

Background: Agricultural emissions pose significant health risks, especially in countries like India with abundant agricultural waste. This study focuses on understanding stubble burning perceptions and practices in rural National Capital Region to inform targeted interventions for sustainable farming practices and improved public health. Methods and Material: This community-based cross-sectional study was conducted among the randomly selected households of rural Ballabgarh, Haryana. A pre-tested, semi-structured questionnaire was used to obtain information on perception and practices on stubble burning. Data were collected in Epicollect 5 and analyzed in STATA 14. Results: Of the 2000 households approached, 1813 responded with a response rate of 90.7%. Around 53% of the study participants believed that vehicular pollution is the main reason for air pollution, and 90% of them were unaware of the Government schemes related to stop stubble burning and with respect to the practices of stubble disposal. Around 70% of the participants mentioned that respiratory illness is the most severe effect of air pollution. Conclusion: The public was mostly unaware of the government’s efforts to reduce stubble burning. Health promotion initiatives must be carried out to raise community knowledge about the programs available to combat stubble burning, therefore decreasing air pollution and its health implications.

Abstract Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.

Abstract Background In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites. Methods This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants’ fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants’ inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables. Results We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants’ mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8–1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20–1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04–11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory. Conclusions Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.

Background: Peroneus longus tendon (PLT) autograft has emerged as one of the primary graft options for arthroscopic anterior cruciate ligament reconstruction (ACLR). We aimed to study whether PLT autograft could be used as primary graft for arthroscopic single bundle ACLR, without compromising stability of donor ankle. Materials and Methods: A prospective observational study of 120 patients, who underwent single bundle arthroscopic ACLR with ipsilateral PLT autograft was done. Functional outcome of patients were evaluated with international knee documentation (IKDC) and Lysholm knee scores after one year. The donor ankle morbidity was assessed using American orthopedic foot and ankle score (AOFAS) and foot and ankle disability index (FADI) scores. Results: The mean IKDC pre-op subjective score was 55.3 ± 10.7 and after one year follow-up was 91.4 ± 5.86. The mean difference of IKDC score between pre-op and post-op evaluation was 33.1 ± 11.4, with a p-value of

Abstract Background This paper describes changes in the prevalence and intensity of schistosome parasite infections in a project integrating mass drug administration (MDA), water, sanitation, and hygiene (WaSH), and behavioral change interventions. Methods The Geshiyaro Project comprises three intervention arms. Arm 1 is subdivided into “Arm 1 pilot” (one district) and Arm 1 (four other districts), both receiving integrated community-wide MDA with intensive WaSH interventions. Arm 2 involves 17 districts with community-wide MDA interventions, while Arm 3 serves as a control with school-based MDA interventions in three districts. A total of 150 individuals, stratified by age group, were randomly selected from each of the 45 sentinel sites. Arm sizes were 584 (Arm 1 pilot), 1636 (Arm 1), 2203 (Arm 2), and 2238 (Arm 3). Statistical tests were employed to compare infection prevalence and intensity across the different arms. Results The prevalence of schistosome parasite infection ranged from 0% to 2.6% and from 1.7% to 25.7% across districts, employing the Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) diagnostics, respectively. The mean infection intensity level showed no marked difference between baseline and follow-up surveys when measured by KK, except in Arm 2 (t = 6.89, P

Objective: To describe the outcomes of training nephrology clinicians and clinical research participants, to use the Best Case/Worst Case Communication intervention, for discussions about dialysis initiation for patients with life-limiting illness, during a randomized clinical trial to ensure competency, fidelity to the intervention, and adherence to study protocols and the intervention throughout the trial. Methods: We enrolled 68 nephrologists at ten study sites and randomized them to receive training or wait-list control. We collected copies of completed graphic aids (component of the intervention), used with study-enrolled patients, to measure fidelity and adherence. Results: We trained 34 of 36 nephrologists to competence and 27 completed the entire program. We received 60 graphic aids for study-enrolled patients for a 73% return rate in the intervention arm. The intervention fidelity score for the graphic aid reflected completion of all elements throughout the study. Conclusion: We successfully taught the Best Case/Worst Case Communication intervention to clinicians as research participants within a randomized clinical trial. Innovation: Decisions about dialysis are an opportunity to discuss prognosis and uncertainty in relation to consideration of prolonged life supporting therapy. Our study reveals a strategy to evaluate adherence to a communication intervention in real time during a clinical study.

The rising problem of plastic pollution is becoming one of the major environmental issues for the world. In the ocean, plastics undergo degradation into smaller microplastics (MPs) and nanoplastics (NPs). Wild fish and farmed salmon would likely be exposed to these NPs and MPs both through skin and through skin wounds. Keratocyte cells, located in the skin epithelial layer, are scavenger cells which may remove foreign materials and maintain the salmon’s health. They are therefore first in line to handle and to suffer from MP and NP exposure. While the impacts of MPs have been well studied in many different organisms, much less is known about the effects of NP exposure, particularly at the subcellular level. Here, we have used holotomographic and fluorescence microscopy to show that both skin and corneal salmon keratocyte cells fully internalize 500–1000 nm polystyrene particles, as well as inorganic 500 nm silica particles. The fact that corneal epithelial cells also take up particles is novel. Furthermore, some of these particles likely end up in lysosomal compartments within 2 hours of exposure. Here, we show that both conventional and new modalities of microscopy have a role to play to understand how micro- and nano particles affect epithelial cells.

Decreased water quality in coastal environments due to land alterations by human activities has caused stressed and degraded coral reefs worldwide. The consequences of decreased water quality are not limited to coral reefs but also affect the quality of people’s lives by increasing the incidence of diseases, so areas highly impacted have been prioritized for management. The Guánica Bay Watershed Management Plan was developed to reduce the non-point sources of pollution that arrive at the bay and to protect adjacent coral reefs, however, 15 years have passed since its creation and management actions have not been evaluated. The purpose of this study was to evaluate the effectiveness of the management actions implemented in the Guánica Bay watershed. Therefore, the objective of this study was to describe temporal trends (2002–2008 and 2016–2022) of remotely sensed diffuse attenuation coefficient at 490 nm (Kd490), a water quality indicator, in one managed (Guánica Bay) and three non-managed (Guayanilla Bay, Descalabrado River, and Guanajibo River) estuaries in Southwestern Puerto Rico. This was achieved by integrating ocean-color satellite imagery from MERIS-Envisat and OLCI-Sentinel-3 sensors that were sampled using a beyond-Before-After-Control-Impact (beyond-BACI) approach. An additional oceanic site was selected to evaluate continuity between sensors estimates. The imagery was processed using SNAP to extract Kd490 values in the estuaries. The analysis for the beyond-BACI found significant differences between periods (before and after) but the changes were unique to each location within estuary. The lowest Kd490 values and variability within estuary was observed in Guánica (range 0.05–0.1 m-1) and the highest Kd490 values were observed in Guayanilla (0.35 m-1). The southern estuaries showed similar temporal trends, all having a peak in 2018 and a trough in 2020. Kd490 did not decrease in Guánica after the implementation of management actions, which can be related to the passage of several hurricanes during the after period. Further analysis should be done as new data is available and after the implementation of the last management actions suggested in the plan.

Physical properties of biological membranes directly or indirectly govern biological processes. Yet, the interplay between membrane and integral membrane proteins is difficult to assess due to reciprocal effects between membrane proteins, individual lipids, and membrane architecture. Using solid-state NMR (SSNMR) we previously showed that KirBac1.1, a bacterial Inward-Rectifier K+ channel, nucleates bilayer ordering and microdomain formation through tethering anionic lipids. Conversely, these lipids cooperatively bind cationic residues to activate the channel and initiate K+ flux. The mechanistic details governing the relationship between cooperative lipid loading and bilayer ordering are, however, unknown. To investigate, we generated KirBac1.1 samples with different concentrations of 13C-lableded phosphatidyl glycerol (PG) lipids and acquired a full suite of SSNMR 1D temperature series experiments using the ordered all-trans (AT) and disordered trans-gauche (TG) acyl conformations as markers of bilayer dynamics. We observed increased AT ordered signal, decreased TG disordered signal, and increased bilayer melting temperature with increased PG concentration. Further, we identified cooperativity between ordering and direct binding of PG lipids, indicating KirBac1.1-driven bilayer ordering and microdomain formation is a classically cooperative Hill-type process driven by and predicated upon direct binding of PG lipids. Our results provide unique mechanistic insight into how proteins and lipids in tandem contribute to supramolecular bilayer heterogeneity in the lipid membrane.

Abstract Background Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids. Methods This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers. Results We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using “down”, heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again. Conclusions Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS.

Traumatic brain injury (TBI) is a common diagnosis requiring acute hospitalization. Long-term, TBI is a significant source of health and socioeconomic impact in the United States and globally. The goal of clinicians who manage TBI is to prevent secondary brain injury. In this population, post-traumatic cerebral infarction (PTCI) acutely after TBI is an important but under-recognized complication that is associated with negative functional outcomes. In this comprehensive review, we describe the incidence and pathophysiology of PTCI. We then discuss the diagnostic and treatment approaches for the most common etiologies of isolated PTCI, including brain herniation syndromes, cervical artery dissection, venous thrombosis, and post-traumatic vasospasm. In addition to these mechanisms, hypercoagulability and microcirculatory failure can also exacerbate ischemia. We aim to highlight the importance of this condition and future clinical research needs with the goal of improving patient outcomes after TBI.

Background and Study Aim. Dehydration is a condition where there is a lack of fluid in the body, accompanied by disturbances in the body's metabolic processes. This study aims to prove the effect of dehydration on 5 lap running by comparing the pulse rate before and after dehydration. Materials and Methods. This study used an experimental method. The population in this research is Tanjungpura University sports students. Purposive sampling technique so that a sample of 19 students was obtained. The sample consists of 4 women and 15 men. In the research, the implementation procedure will be to measure 2000 meter running performance before and after losing fluid, weighing body weight to precision ounces. Analysis was assisted using SPSS 26. Results. The results of the analysis showed a significance value of 0.000

In this study, a silica matrix was utilized as a substrate for zinc oxide nanoparticles (ZnO NPs) to enhance their photocatalytic activity for the degradation of methylene blue (MB) dye. The recovery of the prepared material was also investigated. To compare the performance of the prepared material with ZnO NPs and bare silica, various analyses were conducted. ZnO NPs were synthesized via a coprecipitation method and characterized using Fourier-transform infrared spectra and X-ray diffraction (XRD). The XRD results revealed highly crystalline ZnO NPs with an average crystallite size of less than 100 nm. The presence of ZnO on the silica matrix was confirmed using scanning electron microscopy (SEM) and EDX analysis. The prepared ZnO NPs showed enhanced photocatalytic activity for the degradation of MB dye, and reasonable material recovery was also observed. The silica-coated ZnO NPs degraded MB dye by 97% in just 40 min and retained their photocatalytic activity for up to 20 cycles. In comparison, bare silica exhibited effective photodegradation but lost its photodegradation capacity after five cycles. ZnO NPs without silica coating took 5 h to degrade MB dye. The significant accomplishment in this study is the development of novel materials with high recoverability, simple preparation, and efficient photocatalytic activity. In the future, ZnO NPs supported on a silica matrix can be utilized for various applications.

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often phylogenetically related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and able to infect both mosquitoes and vertebrates. ISVs can also induce a phenomenon called “superinfection exclusion”, whereby a primary ISV infection in an insect inhibits subsequent viral infections of the insect. This has sparked interest in the use of ISVs for the control of pathogenic arboviruses transmitted by mosquitoes. In particular, insect-specific flaviviruses (ISFs) have been shown to inhibit infection of vertebrate-infecting flaviviruses (VIFs) both in vitro and in vivo. This has shown potential as a new and ecologically friendly biological approach to the control of arboviral disease. For this intervention to have lasting impacts for biological control, it is imperative that ISFs are maintained in mosquito populations with high rates of vertical transmission. Therefore, these strategies will need to optimise vertical transmission of ISFs in order to establish persistently infected mosquito lines for sustainable arbovirus control. This review compares recent observations of vertical transmission of arboviral and insect-specific flaviviruses and potential determinants of transovarial transmission rates to understand how the vertical transmission of ISFs may be optimised for effective arboviral control.

Plant biomass is the largest and amply available biomass on the earth. Petals of flowering plants serve as an excellent raw material to synthesize nanoparticles. Biologically prepared silver nanoparticles (AgNPs) have garnered interest due to their simple and cost-effective green approach compared to chemical and physical methods. This investigation aimed to analyze the antibacterial, antioxidant, and antibiofilm properties of AgNPs synthesized from Hibiscus Sabdariffa L. petal extract and assess their potential as a stabilizing agent. A surface plasmon resonance peak at 421 nm confirmed the formation of AgNPs in the ultraviolet–visible (UV–vis) range. Additionally, size and morphological studies of the AgNPs were obtained using Scanning electron microscope (SEM) and X-ray diffraction (XRD) techniques. The identification of functional groups that are responsible for the stabilizing layer of AgNPs was achieved through Fourier transform infrared spectroscopy (FTIR) analysis. The antioxidant activity of synthesized AgNPs was investigated using the DPPH and ABTS radicals; the best performance was found in the scavenging of the DPPH radical, with an IC50 value of 37.71 ± 0.07 μg/ml. AgNPs actively suppressed the growth of four pathogenic bacteria (Shigella dysenteriae, Shigella boydii, Staphylococcus aureus, and Escherichia coli). Notably, Escherichia coli biofilm formation was absent at 40 and 80 g/ml of AgNPs up to 96 h. Finally, the overall findings of this present study confirmed that the AgNPs prepared from Hibiscus Sabdariffa petal extract can be used as antioxidant, antimicrobial, and antibiofilm preparations.

Purpose: To investigate the simultaneous effect of 3-dimensional (3D) hinge axis (HA) orientation on alignment parameters in all 3 anatomical planes in high tibial osteotomy. Methods: A computed tomography–based 3D model of a human tibia/fibula was used to establish a 3D tibial coordinate system based on the tibial mechanical axis. In here, an HA was positioned and an opening-wedge high tibial osteotomy with a rotation angle of 10° over the HA was simulated. HA rotation in the axial plane ranged from 0° to 90° and HA tilt relative to the axial plane ranged from –20° to +20°. The study quantified the simultaneous effect of HA orientation on change of alignment parameters in all anatomical reference planes. Results: HA rotation within the tibial axial plane between orientations perpendicular to the coronal and sagittal planes primarily affected both coronal and sagittal plane alignment, with an inverse relationship between these planes (range: 0°-9.7°); the effect of HA rotation on the change in axial plane alignment was maximally 0.9°. In contrast, HA tilt relative to the tibial axial plane primarily affected axial alignment (maximum change: 6.9°); the effect on change in both coronal and sagittal plane alignment was maximally 0.6°. Conclusions: HA rotation in the tibial axial plane primarily affects sagittal and coronal plane alignment, and HA tilt relative to the tibial axial plane primarily affects axial plane alignment. Clinical Relevance: Integrating 3D HA orientation in malalignment planning and correction offers the potential to minimize unintended corrections in nontargeted planes in uniplanar correction osteotomies and to facilitate intentional multiplanar correction with a single osteotomy.

Asim Roy,1 Diane Ito,2 Susan Morris,3 Shawn Candler,4 Judi Profant,3 Charles Bae5 1Ohio Sleep Medicine Institute, Dublin, OH, USA; 2Stratevi LLC, Santa Monica, CA, USA; 3Jazz Pharmaceuticals, Palo Alto, CA, USA; 4Jazz Pharmaceuticals, Philadelphia, PA, USA; 5Penn Sleep Center, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Asim Roy, Ohio Sleep Medicine Institute, 4975 Bradenton Avenue, Dublin, OH, 43017, USA, Tel +1 614-766-0773, Fax +1 614-766-2599, Email aroy@sleepmedicine.comPurpose: Real-world data regarding divided nightly dosing of oxybate and individualized prescribing in patients with narcolepsy are limited. Study objectives were to understand oxybate prescribing practices, including optimizing dose regimens and adjusting dosing per occasional changes in patients’ routines, and physician recommendations for representative patient scenarios.Patients and Methods: A cross-sectional, web- and audio-based survey of physicians treating ≥ 2 patients with narcolepsy, prescribed nightly oxybate (sodium oxybate) dosing for ≥ 6 months, was conducted. Physicians were surveyed on patients’ usual oxybate dosing regimens, frequency of and reasons for oxybate dosing-related discussions, and preferred methods for and perceptions of adjusting oxybate dosing. Physicians provided dosing-related guidance for 4 representative scenarios.Results: Participating physicians (N=25) were neurologists (52%), psychiatrists (44%), and neuropsychiatrists (4%). Individualized oxybate prescribing practices were reflected by the variability of physicians’ reporting of the percentage of their patients being prescribed once-nightly, twice-nightly, and thrice-nightly dosing regimens. Most physicians (68%) reported discussing adjusting individualized treatment to accommodate occasional changes to patients’ routines; the most common reasons were consuming contraindicated beverages (alcohol; 65%) and travel (59%). Adjusting total nightly dose (68%) and dose timing (68%) were preferred adjustment methods. Most physicians (88%) felt the ability to individualize oxybate dosing was important and had a positive impact on ability to provide care. For each representative scenario, physicians provided several dose-adjustment recommendations, and physician responses encouraged patient participation in treatment decision-making.Conclusion: Physicians provided guidance supportive of oxybate dose adjustments to accommodate occasional changes in patients’ routines, and perceived individualized dosing as important in providing care.Plain Language Summary: Why was the research needed?Narcolepsy is an uncommon condition that causes individuals to feel sleepy throughout the day. Other symptoms may include sudden muscle weakness. There is no cure for narcolepsy, but there are several treatments, including medicines known as oxybates. This study focused on how doctors use oxybate to treat patients with narcolepsy.How was the research done?This study was an online survey of doctors who were treating 2 or more patients with narcolepsy. Patients had been taking oxybate for at least 6 months. The survey asked doctors about their patients’ normal oxybate usage, how often and why they discussed oxybate treatment, and which ways oxybate treatment was usually adjusted.What are the results?Twenty-five doctors took part in this study. Most doctors said they discuss personalized treatment to help with occasional changes in their patients’ daily lives. The most common reasons for making treatment changes were consuming alcohol and travel. The most common changes were total nightly amount and timing of oxybate. Most doctors said the ability to personalize oxybate treatment is important and has a positive impact.What does the research mean?This study provides valuable knowledge on real-world oxybate treatment patterns and the conditions when doctors make clinical decisions about treating patients with narcolepsy.Graphical Abstract: Keywords: sodium oxybate, low-sodium oxybate, calcium, magnesium, potassium, sodium oxybates, prescribing patterns, personalized dosing

Achieving negative surgical margins, defined as no tumor found on the edges of the resected tissue, during lumpectomy for breast cancer is critical for mitigating the risk of local recurrence. To identify nonpalpable tumors that cannot be felt, pre-operative placements of wire and wire-free localization devices are typically employed. Wire-free localization approaches have significant practical advantages over wired techniques. In this study, we introduce an innovative localization system comprising a light-emitting diode (LED)-based implantable device and handheld system. The device, which is needle injectable and wire free, utilizes multiple wirelessly powered LEDs to provide direct visual guidance for lumpectomy. Two distinct colors, red and blue, provide a clear indication of tissue depth: blue light is absorbed strongly in tissue, visible within a close range of 2 cm of ex vivo chicken breast and bovine muscle tissue using less than 4 W of transmitted power from a handheld antenna. These miniaturized needle-injectable localization devices show promise for improving surgical guidance of nonpalpable breast tumors.

When performing remote sensing image segmentation, practitioners often encounter various challenges, such as a strong imbalance in the foreground–background, the presence of tiny objects, high object density, intra-class heterogeneity, and inter-class homogeneity. To overcome these challenges, this paper introduces AerialFormer, a hybrid model that strategically combines the strengths of Transformers and Convolutional Neural Networks (CNNs). AerialFormer features a CNN Stem module integrated to preserve low-level and high-resolution features, enhancing the model’s capability to process details of aerial imagery. The proposed AerialFormer is designed with a hierarchical structure, in which a Transformer encoder generates multi-scale features and a multi-dilated CNN (MDC) decoder aggregates the information from the multi-scale inputs. As a result, information is taken into account in both local and global contexts, so that powerful representations and high-resolution segmentation can be achieved. The proposed AerialFormer was benchmarked on three benchmark datasets, including iSAID, LoveDA, and Potsdam. Comprehensive experiments and extensive ablation studies show that the proposed AerialFormer remarkably outperforms state-of-the-art methods.

Background: Previous research has emphasized the significant role of illness perception in chronic diseases, including Multiple Sclerosis. Limited research has been conducted on exploring illness perception in Pediatric Onset Multiple Sclerosis (POMS), parental illness perception, and the impact of differences in their illness perceptions on the emotional well-being of the child. Method: This study included 65 dyads of children aged 10–17 and their parents, divided into the following two groups: (I) 32 dyads of children with POMS and their parents; and (II) 33 dyads of healthy children and their parents. Results: Overall, 73.1% and 43.8% of the children with POMS met the criteria for probable anxiety and depression, respectively, compared to 27.3% and 0% of the healthy children. Differences were found between the dimensions of illness perception in the POMS children and their parents, in the areas of consequences, personal control, identity, and control factors. Multinomial Logistic Regression indicated that differences in child–parent illness perception increased the likelihood of comorbid anxiety and depression by 37%. Discussion: These findings underscore the importance of alignment between children with POMS and their parents in illness perception. Healthcare providers should prioritize interventions that address illness perceptions and be mindful of the potential impact on depression and anxiety comorbidity.

The increasing usage of interconnected devices within the Internet of Things (IoT) and Industrial IoT (IIoT) has significantly enhanced efficiency and utility in both personal and industrial settings but also heightened cybersecurity vulnerabilities, particularly through IoT malware. This paper explores the use of one-class classification, a method of unsupervised learning, which is especially suitable for unlabeled data, dynamic environments, and malware detection, which is a form of anomaly detection. We introduce the TF-IDF method for transforming nominal features into numerical formats that avoid information loss and manage dimensionality effectively, which is crucial for enhancing pattern recognition when combined with n-grams. Furthermore, we compare the performance of multi-class vs. one-class classification models, including Isolation Forest and deep autoencoder, that are trained with both benign and malicious NetFlow samples vs. trained exclusively on benign NetFlow samples. We achieve 100% recall with precision rates above 80% and 90% across various test datasets using one-class classification. These models show the adaptability of unsupervised learning, especially one-class classification, to the evolving malware threats in the IoT domain, offering insights into enhancing IoT security frameworks and suggesting directions for future research in this critical area.

Background: Bipolar disorder (BD) is a mental illness which leads to considerable difficulties and challenges. The neurobiology of BD has complex underpinnings of gene–environment interactions. One such environmental factor, stressful life events (SLEs) can have adverse impacts on the course and prognosis of BD, however, this is underexplored. Aims and objectives: 1) To estimate the frequency and severity of SLEs in patients with BD-current episode depression 2) To determine the association of severity of depression with SLE, sociodemographic and illness-related factors. Methods: This was a cross-sectional study done on 100 consecutive patients diagnosed to have BD-current episode of depression (ICD-10), attending Psychiatry department at Pushpagiri Medical College, Thiruvalla, Kerala. A semi-structured proforma, Hamilton Rating Scale for Depression, Presumptive Stressful Life Events Scale and Brief Psychiatric Rating Scale were used. Results: About 73% of patients reported SLEs – of which 65% had mild/moderate and 8% had severe stress. A statistically significant association was found between SLEs and ‘very severe’ depressive episode. Past suicide attempt, the first episode as depression and lesser duration of the last episode also showed a statistically significant association with severity of depression. Conclusion: As the stressful life experiences have been linked to 'very severe' depressive episodes in a major way, understanding the association of stressful life events and BD can help in predicting further relapses and complications like suicide. It can aid in both symptom reduction and improving quality of life as well.

Throughout history, the utilization of plant products as medicinal remedies has been widespread, with numerous modern drugs finding their origins in the plant kingdom. Taxol, derived from Taxus species, stands out as an exceptional and highly potent anticancer medication. In this study, we present a rapid one-pot synthesis method for silver nanoparticles (AgNPs) using the leaves of Taxus wallichiana Zucca in the presence of sunlight. The synthesized AgNPs were comprehensively characterized using X-ray diffraction, transmission electron microscopy, and HPLC Q-TOF. The AgNPs were further investigated for their antioxidative, anticancer, anti-inflammatory, and antiurolithi properties. The anticancer activity was assessed through a sulforhodamine B assay conducted on the MDA-MB-231 human breast carcinoma cell line and SiHa human cervical cancer cell line. The findings of this study reveal the impressive antioxidative, anticancer, anti-inflammatory, and antiurolithi characteristics exhibited by AgNPs synthesized from leaf extracts. This research highlights an environmentally friendly and cost-effective approach to producing AgNPs by utilizing plant extracts as reducing agents, underscoring the immense potential of natural resources in advancing nanotechnology and its applications.

Abstract Hepatitis C virus (HCV) is a major global health burden as the leading causative agent of chronic liver disease and hepatocellular carcinoma. While the main antigenic target for HCV-neutralizing antibodies is the membrane-associated E1E2 surface glycoprotein, the development of effective vaccines has been hindered by complications in the biochemical preparation of soluble E1E2 ectodomains. Here, we present a cryo-EM structure of an engineered, secreted E1E2 ectodomain of genotype 1b in complex with neutralizing antibodies AR4A, HEPC74, and IGH520. Structural characterization of the E1 subunit and C-terminal regions of E2 reveal an overall architecture of E1E2 that concurs with that observed for non-engineered full-length E1E2. Analysis of the AR4A epitope within a region of E2 that bridges between the E2 core and E1 defines the structural basis for its broad neutralization. Our study presents the structure of an E1E2 complex liberated from membrane via a designed scaffold, one that maintains all essential structural features of native E1E2. The study advances the understanding of the E1E2 heterodimer structure, crucial for the rational design of secreted E1E2 antigens in vaccine development.

Abstract West Nile virus (WNV) causes skin lesions in farmed crocodiles leading to the depreciation of the value of their hides and significant economic losses. However, there is no commercially available vaccine designed for use in crocodilians against WNV. We tested chimeric virus vaccines composed of the non-structural genes of the insect-specific flavivirus Binjari virus (BinJV) and genes encoding the structural proteins of WNV. The BinJV/WNV chimera, is antigenically similar to wild-type WNV but replication-defective in vertebrates. Intramuscular injection of two doses of BinJV/WNV in hatchling saltwater crocodiles (Crocodylus porosus) elicited a robust neutralising antibody response and conferred protection against viremia and skin lesions after challenge with WNV. In contrast, mock-vaccinated crocodiles became viraemic and 22.2% exhibited WNV-induced lesions. This suggests that the BinJV/WNV chimera is a safe and efficacious vaccine for preventing WNV-induced skin lesions in farmed crocodilians.

Context and Background: The specialised land court in Zambia is known as the Lands Tribunal, and it was created in 1996 through the 1995 Lands Act. The Tribunal was established with the objective of achieving speedy, low cost, flexible and efficient means of settling conflicts over land. Inspite of being existence for 27 years, little has been done on the progress and challenges of the Lands Tribunal in resolving conflicts over land in the country. Goal and Objectives: This paper aims at establishing the progress made by the Lands Tribunal in resolving conflicts over land and investigating the challenges faced by the Lands Tribunal in resolving conflicts over land. Methodology: The study incorporated the use of both primary and secondary data collected between January and October 2023. Secondary data were obtained through documents which include peer-reviewed journal articles, theses, books, media, Zambian land laws, and technical reports. Secondary data was supplemented by primary data obtained from three purposively selected institutions: Lands Tribunal, Law Association of Zambia, and Zambia Land Alliance (Kitwe office). The data collection method used with the key informants was in-depth face-to-face interviews. Office management at each institution chose the key informant based on their expertise and experience on the subject. Results: In order to strengthen the Tribunal’s operations, the Lands Tribunal Act of 2010 was enacted, enhancing the Tribunal’s operations by granting it more authority and responsibilities (that is, expanding jurisdiction). Research findings showed that between 2014 and 2023, the Lands Tribunal handled 3318 cases. According to research findings, if the Tribunal was operating efficiently and effectively, it could have handled more than 3,318 cases between 2014 and 2022 considering the numerous problems facing the general courts which adversely affect the general public to resolve their land conflicts. However, the Tribunal could not handle more cases because of various challenges which include inadequate funding, Inadequate staff, poor conditions of service for members of the Tribunal, inadequate transport, delay in the delivery of judgments, low public awareness of the Lands Tribunal, centralised operations of the Lands Tribunal, and forum shopping.

ObjectivesDeworming programmes of soil-transmitted helminths are generally monitored and evaluated by aggregating drug coverage and infection levels at a district level. However, heterogeneity in drug coverage at finer spatial scales means indicators may remain above thresholds for elimination as a public health problem or of transmission in some areas. This paper aims to highlight the misleading information that aggregating data at larger spatial scales can have for programme decision making.MethodsDrug coverage data from the Geshiyaro project were compared at two spatial scales with reference to the World Health Organisation's targets. District (woreda) and village (kebele) level were compared. The association between infection levels and drug coverage was analysed by fitting a weighted least-squares function to the mean intensity of infection (eggs per gram of faeces) against drug coverage.ResultsThe data show clearly that when the evaluation of coverage is aggregated to the district level, information on heterogeneity at a finer spatial scale is lost. Infection intensity decreases significantly (p = 0.0023) with increasing drug coverage.ConclusionAggregating data at large spatial scales can result in prematurely ceasing deworming, prompting rapid infection bounce-back. There is a strong need to define context-specific spatial scales for monitoring and evaluating intervention programmes.

IntroductionStructured medication reviews (SMRs), introduced in the United Kingdom (UK) in 2020, aim to enhance shared decision-making in medication optimisation, particularly for patients with multimorbidity and polypharmacy. Despite its potential, there is limited empirical evidence on the implementation of SMRs, and the challenges faced in the process. This study is part of a larger DynAIRx (Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity) project which aims to introduce Artificial Intelligence (AI) to SMRs and develop machine learning models and visualisation tools for patients with multimorbidity. Here, we explore how SMRs are currently undertaken and what barriers are experienced by those involved in them.MethodsQualitative focus groups and semi-structured interviews took place between 2022-2023. Six focus groups were conducted with doctors, pharmacists and clinical pharmacologists (n = 21), and three patient focus groups with patients with multimorbidity (n = 13). Five semi-structured interviews were held with 2 pharmacists, 1 trainee doctor, 1 policy-maker and 1 psychiatrist. Transcripts were analysed using thematic analysis.ResultsTwo key themes limiting the effectiveness of SMRs in clinical practice were identified: 'Medication Reviews in Practice' and 'Medication-related Challenges'. Participants noted limitations to the efficient and effectiveness of SMRs in practice including the scarcity of digital tools for identifying and prioritising patients for SMRs; organisational and patient-related challenges in inviting patients for SMRs and ensuring they attend; the time-intensive nature of SMRs, the need for multiple appointments and shared decision-making; the impact of the healthcare context on SMR delivery; poor communication and data sharing issues between primary and secondary care; difficulties in managing mental health medications and specific challenges associated with anticholinergic medication.ConclusionSMRs are complex, time consuming and medication optimisation may require multiple follow-up appointments to enable a comprehensive review. There is a need for a prescribing support system to identify, prioritise and reduce the time needed to understand the patient journey when dealing with large volumes of disparate clinical information in electronic health records. However, monitoring the effects of medication optimisation changes with a feedback loop can be challenging to establish and maintain using current electronic health record systems.

BackgroundThe Women's Health Needs Study (WHNS) collected information on the health characteristics, needs, and experiences, including female genital mutilation (FGM) experiences, attitudes, and beliefs, of women aged 18 to 49 years who were born, or whose mothers were born, in a country where FGM is prevalent living in the US. The purpose of this paper is to describe the WHNS design, methods, strengths and limitations, as well as select demographic and health-related characteristics of participants.MethodsWe conducted a cross-sectional survey from November 2020 -June 2021 in four US metropolitan areas, using a hybrid venue-based sampling (VBS) and respondent-driven sampling (RDS) approach to identify women for recruitment.ResultsOf 1,132 participants, 395 were recruited via VBS and 737 RDS. Most were born, or their mothers were born, in either a West African country (Burkina Faso, Guinea, Mali, Mauritania, Sierra Leone, The Gambia) (39.0%) or Ethiopia (30.7%). More than a third were aged 30-39 years (37.5%) with a majority who immigrated at ages ≥13 years (86.6%) and had lived in the United States for ≥5 years (68.9%). Medicaid was the top health insurer (52.5%), followed by private health insurance (30.5%); 17% of participants had no insurance. Nearly half of women reported 1-2 healthcare visits within the past 12 months (47.7%). One in seven did not get needed health care due to cost (14.8%). Over half have ever used contraception (52.1%) to delay or avoid pregnancy and 76.9% had their last pelvic and/or Papanicolaou (pap) exam within the past 3 years. More than half experienced FGM (55.0%). Nearly all women believed that FGM should be stopped (92.0%).ConclusionThe VBS/RDS approach enabled recruitment of a diverse study population. WHNS advances research related to the health characteristics, needs, and experiences of women living in the US from countries where FGM is prevalent.

Objective: The coronavirus disease 2019 (COVID-19) public health emergency has disproportionately affected older adults and their caregivers, requiring evidence-based and coordinated efforts to meet their health and social needs. This paper describes the role of the CDC Foundation as a knowledge broker working with public health partners to rapidly meet the unmet health, social, and other needs of older adults and caregivers during the COVID-19 pandemic. Type of program or service: Qualitative case study using the Role Model for Knowledge Brokering framework to describe a project that translated public health research into practice during the COVID-19 pandemic response. Methods: This case study documents the experiences of a US-based foundation serving as a knowledge broker, carrying out three roles: establishing research partnerships to study unmet health, social, and other needs of older adults and caregivers during COVID-19; coordinating with partners to identify evidence-based strategies; and rapidly implementing four emergency response pilot projects. Results: The emergency response pilot projects created included: an online resource library – ­SearchFindHelp.org – of public health programs and resources for organisations serving older adults and caregivers; digital literacy training for older adults and caregivers; multicultural caregiver tools to serve rural and Asian American and Pacific Islander older adults; and a grant program to expand local, direct services for older adults. SearchFindHelp.org had 46 781 new users and 101 908 total views from June 2021–March 2023. Older adults and caregivers who participated in digital literacy training from May–September 2021 were more likely to find health resources online and schedule and attend an online doctor’s visit. A paid media campaign in December 2021 was launched to raise awareness of multicultural caregiver tools. Ten community organisations expanded direct, local services for older adults. Lessons learnt: This project highlights the valuable role a foundation can play as a knowledge broker in rapidly translating research into practice during a public health emergency response, to address emerging community needs.

Background: The use of telehealth for the management and treatment of hypertension and cardiovascular disease (CVD) has increased across the United States (U.S.), especially during the COVID-19 pandemic. Telehealth has the potential to reduce barriers to accessing health care and improve clinical outcomes. However, implementation, outcomes, and health equity implications related to these strategies are not well understood. The purpose of this review was to identify how telehealth is being used by U.S. health care professionals and health systems to manage hypertension and CVD and to describe the impact these telehealth strategies have on hypertension and CVD outcomes, with a special focus on social determinants of health and health disparities. Methods: This study comprised a narrative review of the literature and meta-analyses. The meta-analyses included articles with intervention and control groups to examine the impact of telehealth interventions on changes to select patient outcomes, including systolic and diastolic blood pressure. A total of 38 U.S.-based interventions were included in the narrative review, with 14 yielding data eligible for the meta-analyses. Results: The telehealth interventions reviewed were used to treat patients with hypertension, heart failure, and stroke, with most interventions employing a team-based care approach. These interventions utilized the expertise of physicians, nurses, pharmacists, and other health care professionals to collaborate on patient decisions and provide direct care. Among the 38 interventions reviewed, 26 interventions utilized remote patient monitoring (RPM) devices mostly for blood pressure monitoring. Half the interventions used a combination of strategies (e.g., videoconferencing and RPM). Patients using telehealth saw significant improvements in clinical outcomes such as blood pressure control, which were comparable to patients receiving in-person care. In contrast, the outcomes related to hospitalizations were mixed. There were also significant decreases in all-cause mortality when compared to usual care. No study explicitly focused on addressing social determinants of health or health disparities through telehealth for hypertension or CVD. Conclusions: Telehealth appears to be comparable to traditional in-person care for managing blood pressure and CVD and may be seen as a complement to existing care options for some patients. Telehealth can also support team-based care delivery and may benefit patients and health care professionals by increasing opportunities for communication, engagement, and monitoring outside a clinical setting.