'Our culture makes us strong': Understanding and working with community strengths among Aboriginal people in western Sydney.

BACKGROUND: Strengths-based approaches to health care are often seen as an alternative to deficit-based approaches and are common in Aboriginal health settings. Despite this, there is little existing research that describes Aboriginal peoples' perspectives about the strengths of their communities. This paper describes cultural strengths and resources as understood by Aboriginal people living in western Sydney. METHODS: In-depth interviews were used to collect qualitative data from two communities on Dharug and Dharrawal Country in western Sydney Australia. Data come from a larger study, which focused on how cultural strengths supported sexual well-being. Fifty-two interviews were conducted with Aboriginal young people (aged 16-24 years) by trained peer interviewers. Additionally, 16 interviews with Aboriginal adults (25 years and older) were conducted by members of the research team. FINDINGS AND DISCUSSION: While opinions varied, four key areas of cultural strength were identified: (1) strong kinship relationships; (2) knowledge sharing; (3) shared experiences, identities, and values; and (4) knowing Country. Throughout these four themes, the sense of connection and belonging is viewed as an important overarching theme. CONCLUSION: Communities are not homogenous with regard to what they view as cultural strengths. Knowing Country and practising culture meant different things to different individuals while providing a similar sense of belonging, connection, and identity. SO WHAT: Health service providers, policies, and programs can use this information to understand the continuing impacts of past policies and events whilst recognising that each community has strengths that can be drawn upon to improve service engagement, knowledge sharing, and health outcomes.

Genomic Surveillance and Evolutionary Dynamics of Influenza A Virus in Sri Lanka.

Background: Influenza A has been named as a priority pathogen by the WHO due to the potential to cause pandemics. Genomic sequencing of influenza strains is important to understand the evolution of the influenza strains and also to select the appropriate influenza vaccines to be used in the different influenza seasons in Sri Lanka. Therefore, we sought to understand the molecular epidemiology of the influenza viruses in the Western Province of Sri Lanka, including mutational analysis to investigate the evolutionary dynamics. Methodology: A total of 349 individuals presenting with fever and respiratory symptoms were enrolled in this study from November 2022 to May 2024. Nasopharyngeal and oropharyngeal specimens were collected and screened using quantitative PCR to detect Influenza A, Influenza B, and SARS-CoV-2. Subtyping and genomic sequencing was carried out on influenza A strains using Oxford Nanopore Technology. Results: Influenza A was detected in 49 (14 %) patients, influenza B in 20 (5.7%) and SARS-CoV-2 in 41 (11.7%). Co-infections were observed in five participants. The phylogenetic analysis assigned the H1N1 HA gene sequences within the 6B.1A.5a.2a clade. The HA gene of the H1N1 sequences in 2023 were assigned as belonging to the subclades C.1, C.1.2, and C.1.8, while the 2024 sequences were assigned to subclades C.1.8 and C.1.9. The H3N2 sequences from 2023 were assigned to the 3C.2a1b.2a.2a.1b clade and subclade G.1.1.2, while the 2024 sequences were assigned to the 3C.2a1b.2a.2a.3a.1 clade and subclade J.2. The K54Q, A186T, Q189E, E224A, R259K, K308R, I418V, and X215A amino acid substitutions were seen in the H1N1 in the 2023 and 2024 sequences. The 2024 H1N1 sequences additionally exhibited further substitutions, such as V47I, I96T, T120A, A139D, G339X, K156X, and T278S. Conclusion: In this first study using genomic sequencing to characterize the influenza A strains in Sri Lanka, which showed different influenza A viruses circulating in an 18-month period. As the Sri Lankan strains also had certain mutations of unknown significance, it would be important to continue detailed surveillance of the influenza strains in Sri Lanka to choose the most suitable vaccines for the population and the timing of vaccine administration.

Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages.

BACKGROUND: While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity. METHODS: Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1ß levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF. RESULTS: Significantly higher levels of IL-1ß were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1ß when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF. CONCLUSIONS: As RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.

Continuous quality improvement in a community-wide TB screening and prevention programme in Papua New Guinea.

SETTING: Daru Island in Papua New Guinea (PNG) has a high prevalence of TB and multidrug-resistant TB (MDR-TB). OBJECTIVE: To evaluate the early implementation of a community-wide project to detect and treat TB disease and infection, outline the decision-making processes, and change the model of care. DESIGN: A continuous quality improvement (CQI) initiative used a plan-do-study-act (PDSA) framework for prospective implementation. Care cascades were analysed for case detection, treatment, and TB preventive treatment (TPT) initiation. RESULTS: Of 3,263 people screened for TB between June and December 2023, 13.7% (447/3,263) screened positive (CAD4TB or symptoms), 77.9% (348/447) had Xpert Ultra testing, 6.9% (24/348) were diagnosed with TB and all initiated treatment. For 5-34-year-olds without active TB (n = 1,928), 82.0% (1,581/1,928) had tuberculin skin testing (TST), 96.1% (1,519/1,581) had TST read, 23.0% (350/1,519) were TST-positive, 95.4% (334/350) were TPT eligible, and 78.7% (263/334) initiated TPT. Three PDSA review cycles informed adjustments to the model of care, including CAD4TB threshold and TPT criteria. Key challenges identified were meeting screening targets, sputum unavailability from asymptomatic individuals with high CAD4TB scores, and consumable stock-outs. CONCLUSION: CQI improved project implementation by increasing the detection of TB disease and infection and accelerating the pace of screening needed to achieve timely community-wide coverage.

CONTEXTE: L'île de Daru en Papouasie-Nouvelle-Guinée (PNG) présente une forte prévalence de la TB et de la TB multirésistante (MDR-TB). OBJECTIF: Évaluer la mise en œuvre précoce d'un projet à l'échelle de la communauté pour détecter et traiter la TB et l'infection, décrire les processus de prise de décision et changer le modèle de soins. CONCEPTION: Une initiative d'amélioration continue de la qualité (CQI, pour l'anglais « continuous quality improvement ¼) a utilisé un cadre de planification, d'action, d'étude, d'action (PDSA, pour l'anglais «plan-do-study-act ¼) pour la mise en œuvre prospective. Les cascades de soins ont été analysées pour la détection des cas, le traitement et l'initiation du traitement préventif de la TB. RÉSULTATS: Sur 3 263 personnes dépistées pour la TB entre juin et décembre 2023, 13,7% (447/3 263) ont été dépistées positives (CAD4TB ou symptômes), 77,9% (348/447) ont subi un test Xpert Ultra, 6,9% (24/348) ont reçu un diagnostic de TB et toutes ont commencé un traitement. Chez les 5 à 34 ans sans TB active (n = 1 928), 82,0% (1 581/1 928) ont subi un test cutané à la tuberculine (TCT), 96,1% (1 519/1 581) ont eu un test de dépistage du TCT, 23,0% (350/1 519) étaient positifs au TCT, 95,4% (334/350) étaient éligibles au TPT et 78,7% (263/334) ont initié le TPT. Trois cycles d'examen PDSA ont permis d'ajuster le modèle de soins, y compris le seuil CAD4TB et les critères TPT. Les principaux défis identifiés étaient l'atteinte des objectifs de dépistage, l'indisponibilité des expectorations chez les personnes asymptomatiques avec des scores CAD4TB élevés et les ruptures de stock de consommables. CONCLUSION: L'ACQ a amélioré la mise en œuvre du projet en augmentant la détection de la TB et de l'infection et en accélérant le rythme de dépistage nécessaire pour atteindre une couverture à l'échelle de la communauté en temps opportun.

Operational research highlights ongoing challenges for comprehensive TB services in Papua New Guinea.

Papua New Guinea (PNG) is a high-burden country for TB, with an estimated annual TB incidence rate of 432 per 100,000 population. There are major challenges to the provision of quality care for TB patients with high rates of loss to follow-up, and multidrug-resistant TB is increasingly detected. In 2022-2023, the second Structured Operational Research Training IniTiative (SORT-IT) for TB was undertaken. Eight participants completed the course, and the outputs from these research projects highlight important current operational issues for the PNG TB programme in a range of settings. The first four articles in the series are published in this issue of Public Health Action, with the remainder to follow in subsequent issues.

Loss to follow-up among adults with drug-resistant TB in Papua New Guinea.

SETTING: Multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) is now endemic in the National Capital District (NCD), Papua New Guinea. Loss to follow-up (LTFU) is a challenge. OBJECTIVE: To evaluate and identify risk factors for LTFU, including pre-treatment LTFU, in adults with MDR/RR-TB at Port Moresby General Hospital (PMGH). DESIGN: A retrospective analysis of treatment initiation in adults diagnosed with MDR/RR-TB (2018-2022) and outcomes for a cohort treated for MDR/RR-TB (2014-2019). We assessed the factors associated with LTFU using multivariate logistic regression. RESULTS: Of 95 patients diagnosed with MDR/RR-TB at PMGH from 2018 to 2022, 21 (22%) were lost to follow-up before treatment. Of the 658 adults who initiated treatment for MDR/RR-TB at PMGH from 2014 to 2019, 161 (24%) were lost to follow-up during treatment. A higher proportion of patients on injectable-containing long regimens (110/404, 27%) were lost to follow-up than those on the all-oral regimen containing bedaquiline (13/66, 12%). Treatment loss to follow-up was associated with age (35-54 years age group: aOR 0.49, 95% CI 0.32-0.77; 55-75 years age group: aOR 0.42, 95% CI 0.19-0.90; compared to the 15-34 years age group), residence outside of NCD (aOR 1.79, 95% CI 1.04-3.06), and year of treatment initiation. CONCLUSION: Pre-treatment LTFU requires programmatic focus. Shorter oral regimens and decentralised services may address the reasons for higher LTFU in younger people and people living outside NCD.

CONTEXTE: La TB multirésistante/résistante à la rifampicine (MDR-TB/RR-TB, pour l'anglais « multidrug/rifampicin-resistant TB ¼) est maintenant endémique dans le district de la capitale nationale (NCD, pour l'anglais « National Capital District ¼), en Papouasie-Nouvelle-Guinée. La perte de suivi (LTFU, pour l'anglais « loss to follow-up ¼) est un défi. OBJECTIF: Évaluer et identifier les facteurs de risque de LTFU, y compris le LTFU avant le traitement, chez les adultes atteints de MDR-TB/RR-TB à Port Moresby General Hospital (PMGH). CONCEPTION: Une analyse rétrospective de l'initiation du traitement chez les adultes diagnostiqués avec une MDR-TB/RR-TB (2018­2022) et des résultats pour une cohorte traitée pour la MDR-TB/RR-TB (2014­2019). Nous avons évalué les facteurs associés au LTFU à l'aide d'une régression logistique multivariée. RÉSULTATS: Sur les 95 patients diagnostiqués avec une MDR-TB/RR-TB à PMGH de 2018 à 2022, 21 (22%) ont été perdus de vue avant le traitement. Sur les 658 adultes qui ont commencé un traitement pour la MDR-TB/RR-TB à PMGH entre 2014 et 2019, 161 (24%) ont été perdus de vue pendant le traitement. Une proportion plus élevée de patients recevant des régimes longs contenant des injectables (110/404 ; 27%) ont été perdus de vue que ceux recevant un régime entièrement oral contenant de la bédaquiline (13/66 ; 12%). La perte de traitement au suivi était associée à l'âge (groupe d'âge de 35 à 54 ans : aOR 0,49 ; IC à 95% 0,32 à 0,77 ; groupe d'âge de 55 à 75 ans : aOR 0,42 ; IC à 95% 0,19 à 0,90 ; par rapport au groupe d'âge de 15 à 34 ans), à la résidence en dehors des NCD (aOR 1,79 ; IC à 95% 1,04 à 3,06) et à quelques années de début de traitement. CONCLUSION: Le LTFU avant le traitement nécessite une orientation programmatique. Des régimes oraux plus courts et des services décentralisés peuvent s'attaquer aux raisons de l'augmentation du LTFU chez les jeunes et les personnes vivant en dehors des NCD.

Current State of Evidence-Based Long-Term Monitoring Protocols for Breast Plastic Surgery Patients.

BACKGROUND: Recommendations for breast surveillance following breast plastic surgery are frequently changing. Establishing guidelines for long-term monitoring protocols may help identify treatable conditions and prevent untoward sequelae. We sought to evaluate the current state of evidence-based long-term monitoring protocols for patients following breast augmentation, reduction, and breast reconstruction. METHODS: Official guidelines from various American societies and international societies were analyzed for alignment in evidence-based recommendations regarding breast surveillance. RESULTS: The most recent US FDA update recommends magnetic resonance imaging or ultrasound starting 5-6 years after surgery and every 2-3 years thereafter. Discrepancies exist among professional societies: the American Society of Plastic Surgeons (ASPS) aligns with the FDA, while the American Society of Breast Surgeons and American College of Radiology (ACR) find no role for imaging for asymptomatic cases. Ultrasound is first-line for any implant concerns, with MRI if necessary. European societies oppose routine breast implant imaging. Breast reduction patients lack unique screening protocols; monitoring aligns with age and cancer risk factors. Following mastectomy and breast reconstruction, most organizations advocate for annual clinical examinations, with more frequent examinations initially. Evidence suggests that physical examination is sufficient to detect local cancer recurrence, with imaging only indicated if there is concern for recurrence. No surveillance imaging is recommended by the American Society of Clinical Oncology, National Comprehensive Cancer Network, or ASPS; however, ACR recommends mammography for autologous reconstruction only. CONCLUSION: Multispecialty and regulatory body alignment may promote provider and patient adherence. Ongoing studies of long-term outcomes are needed to strengthen the level of evidence for monitoring guidelines.

Artificial Intelligence-Based Indocyanine Green Lymphography Pattern Classification for Management of Lymphatic Disease.

Background: Lymphedema diagnosis relies on effective imaging of the lymphatic system. Indocyanine green (ICG) lymphography has become an essential diagnostic tool, but globally accepted protocols and objective analysis methods are lacking. In this study, we aimed to investigate artificial intelligence (AI), specifically convolutional neural networks, to categorize ICG lymphography images patterns into linear, reticular, splash, stardust, and diffuse. Methods: A dataset composed of 68 ICG lymphography images was compiled and labeled according to five recognized pattern types: linear, reticular, splash, stardust, and diffuse. A convolutional neural network model, using MobileNetV2 and TensorFlow, was developed and coded in Python for pattern classification. Results: The AI model achieved 97.78% accuracy and 0.0678 loss in categorizing images into five ICG lymphography patterns, demonstrating high potential for enhancing ICG lymphography interpretation. The high level of accuracy with a low loss achieved by our model demonstrates its effectiveness in pattern recognition with a high degree of precision. Conclusions: This study demonstrates that AI models can accurately classify ICG lymphography patterns. AI can assist in standardizing and automating the interpretation of ICG lymphographic imaging.

Protocol for a randomized controlled trial of intensive blood pressure control on cardiovascular risk reduction in patients with atrial fibrillation: rationale and design of the CRAFT trial.

BACKGROUND: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHOD: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months post-randomization, and every 6 months thereafter during the study. CONCLUSION: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF.

Restrictive Versus Liberal Transfusion in Patients with Type 1 or Type 2 Myocardial Infarction: A Prespecified Analysis of the Myocardial Ischemia and Transfusion (MINT) Trial.

BACKGROUND: The MINT trial raised concern for harm from a restrictive versus liberal transfusion strategy in patients with acute myocardial infarction (MI) and anemia. Type 1 and type 2 MI are distinct pathophysiological entities that may respond differently to blood transfusion. This analysis sought to determine if the effects of transfusion varied among patients with a type 1 or a type 2 MI and anemia. We hypothesized that the liberal transfusion strategy would be of greater benefit in type 2 than in type 1 MI. METHODS: We compared rates of death or MI at 30 days in patients with type 1 (n=1460) and type 2 (n=1955) MI and anemia who were randomly allocated to a restrictive (threshold of 7 to 8 g/dL) or a liberal (threshold of 10 g/dL) transfusion strategy. RESULTS: The primary outcome of death or MI was observed in 16% of type 1 MI and 15.4% of type 2 MI patients. The rate of death or MI was higher in patients with type 1 MI randomized to a restrictive (18.2%) versus liberal (13.2%) transfusion strategy (RR 1.32, 95% CI 1.04 - 1.67) with no difference observed between the restrictive (15.8% ) and liberal (15.1% ) transfusion strategies in patients with type 2 MI (RR 1.05 95% CI 0.85-1.29). The test for a differential effect of transfusion strategy by MI type was not statistically significant (P-interaction = 0.16). CONCLUSIONS: The concern for harm with a restrictive transfusion strategy in patients with acute MI and anemia raised in the MINT primary outcome manuscript may be more apparent in patients with type 1 than type 2 MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02981407.

Impact of a community-based participatory research project with underserved communities at risk for hepatitis C virus in Ho Chi Minh City, Vietnam: an evaluation study.

BACKGROUND: Participatory approaches have become a widely applied research approach. Despite their popularity, there are many challenges associated with the evaluation of participatory projects. Here we describe an evaluation of a community-based participatory research study of underserved communities in Ho Chi Minh City (HCMC), Vietnam at risk for hepatitis C virus. The goals of our evaluation were to explore the main benefits and challenges of implementing and participating in a participatory study and to describe study impacts. METHODS: We conducted two meetings with leaders and members of the participating groups followed by in-depth interviews with 10 participants. We then held a dissemination meeting with over 70 participants, including the representatives of each group, researchers from non-governmental organizations (community-based, national and international), and govenrment officials from the Vietnam Ministry of Health and the Department of Health of HCMC. RESULTS: Results include four categories where we describe first the participatory impacts, followed by the collaborative impacts. Then we describe the benefits and challenges of creating and belonging to one of the groups, from members' and leaders' points of view. Finally, we describe the key suggestions that participants provided for future research. CONCLUSION: In conclusion, the evaluation approach led to both a research reflection on the 'success' of the project and enabled participants themselves to reflect on the outcomes and benefits of the study from their point of view.

Participatory approaches in research aim to include participants in an array of aspects of the study, including developing research questions, collecting data, conducting analysis, etc. It has become a more popular method, however there are still challenges surrounding the evaluation of these projects. Here we describe an evaluation of a community-based participatory research study of underserved communities in Ho Chi Minh City (HCMC), Vietnam at risk for hepatitis C virus. The goals of the evaluation were to discuss and explore the main benefits and challenges with those who participated, as well as assess study impacts. To conduct the evaluation, we conducted two meetings with leaders and members of the participating groups followed by interviews with 10 people who were involved. The evaluation results included four categories including impacts for members as well as wider impacts in the community. Then we describe the benefits and challenges of creating and belonging to one of the groups, from members' and leaders' points of view. Finally, we describe the key suggestions that participants provided for future research. In conclusion, the evaluation approach led to both a research reflection on the 'success' of the project and enabled participants themselves to reflect on the outcomes and benefits of the study from their point of view.

Syntaxin-6 delays prion protein fibril formation and prolongs the presence of toxic aggregation intermediates.

Prions replicate via the autocatalytic conversion of cellular prion protein (PrPC) into fibrillar assemblies of misfolded PrP. While this process has been extensively studied in vivo and in vitro, non-physiological reaction conditions of fibril formation in vitro have precluded the identification and mechanistic analysis of cellular proteins, which may alter PrP self-assembly and prion replication. Here, we have developed a fibril formation assay for recombinant murine and human PrP (23-231) under near-native conditions (NAA) to study the effect of cellular proteins, which may be risk factors or potential therapeutic targets in prion disease. Genetic screening suggests that variants that increase syntaxin-6 expression in the brain (gene: STX6) are risk factors for sporadic Creutzfeldt-Jakob disease. Analysis of the protein in NAA revealed, counterintuitively, that syntaxin-6 is a potent inhibitor of PrP fibril formation. It significantly delayed the lag phase of fibril formation at highly sub-stoichiometric molar ratios. However, when assessing toxicity of different aggregation time points to primary neurons, syntaxin-6 prolonged the presence of neurotoxic PrP species. Electron microscopy and super-resolution fluorescence microscopy revealed that, instead of highly ordered fibrils, in the presence of syntaxin-6 PrP formed less-ordered aggregates containing syntaxin-6. These data strongly suggest that the protein can directly alter the initial phase of PrP self-assembly and, uniquely, can act as an 'anti-chaperone', which promotes toxic aggregation intermediates by inhibiting fibril formation.

Correction: Facing the escalating burden of dengue: Challenges and perspectives.

[This corrects the article DOI: 10.1371/journal.pgph.0002598.].

Expanding Color Control of Anodically Coloring Electrochromes Based on Electron-Rich 1,4-Dihydropyrrolo[3,2-b]pyrroles.

Anodically coloring electrochromes have received attention in recent years as high-contrast alternatives to cathodically coloring electrochromes due to their superior optical contrast during electrochemical switching. While current systems represent significant progress for organic electrochromics, it is necessary to expand the structural diversity of these materials while simultaneously reducing the hazards associated with synthetic protocols. With these considerations in mind, a family of 1,4-dihydropyrrolo[3,2-b]pyrrole (DHPP) chromophores with varying functionalities along the 2,5-axis was envisioned to accomplish these goals. After predicting different absorbance traits as oxidized molecules with time-dependent density functional theory, DHPP chromophores with varying peripheral functionalities were synthesized in a single aerobic synthetic step via an iron-catalyzed multicomponent reaction and characterized as high-contrast chromophores. In solution, the DHPP chromophores absorb in the ultraviolet region of the electromagnetic spectrum, resulting in color-neutral L*a*b* color coordinates of ∼100, 0, 0. Upon chemical oxidation, each molecule transitions to absorb at various points across the visible spectrum based on the extent of electron-donating ability and can display five distinct colors. Importantly, the chromophores are redox-active and display switching capabilities with an applied electrochemical potential. In conjunction with building fundamental insights into molecular design of DHPP chromophores, the results and synthetic simplicity of DHPPs make them compelling materials for color-controlled high-contrast electrochromes.

Understanding Degradation Dynamics of Azomethine-containing Conjugated Polymers.

Understanding the influence of chemical environments on the degradation properties of conjugated polymers is an important task for the continued development of sustainable materials with potential utility in biomedical and optoelectronic applications. Azomethine-containing polymers were synthesized via palladium-catalyzed direct arylation polymerization (DArP) and used to study fundamental degradation trends upon exposure to acid. Shifts in the UV-vis absorbance spectra and the appearance/disappearance of aldehyde and imine diagnostic peaks within the 1H NMR spectra indicate that the polymers will degrade in the presence of acid. After degradation, the aldehyde starting material was recovered in high yields and was shown to maintain structural integrity when compared with commercial starting materials. Solution-degradation studies found that rates of degradation vary from 5 h to 90 s depending on the choice of solvent or acid used for hydrolysis. Additionally, the polymer was shown to degrade in the presence of perfluoroalkyl substances (PFASs), which makes them potentially useful as PFAS-sensitive sensors. Ultimately, this research provides strategies to control the degradation kinetics of azomethine-containing polymers through the manipulation of environmental factors and guides the continued development of azomethine-based materials.

Odorant transport in a hagfish.

Odorant transport is of fundamental and applied importance. Using computational simulations, we studied odorant transport in an anatomically accurate model of the nasal passage of a hagfish (probably Eptatretus stoutii). We found that ambient water is sampled widely, with a significant ventral element. Additionally, there is a bilateral element to olfactory flow, which enters the single nostril in two narrow, laminar streams that are then split prior to the nasal chamber by the anterior edge of the central olfactory lamella. An appendage on this lamella directs a small portion (10-14%) of the overall nasal flow to the olfactory sensory channels. Much of the remaining flow is diverted away from the sensory channels by two peripheral channels. The anterior edge of the central olfactory lamella, together with a jet-impingement mechanism, disperses flow over the olfactory surfaces. Diffusion of odorant from bulk water to the olfactory surfaces is facilitated by the large surface area:volume ratio of the sensory channels, and by a resistance-based hydrodynamic mechanism that leads to long residence times (up to 4.5 s) in the sensory channels. With increasing volumetric flow rate, the rate of odorant transfer to the olfactory surfaces increases, but the efficiency of odorant uptake decreases, falling in the range 2-6%. Odorant flux decreases caudally across the olfactory surfaces, suggesting in vivo a preponderance of olfactory sensory neurons on the anterior part of each olfactory surface. We conclude that the hagfish has a subtle anatomy for locating and capturing odorant molecules.

In Vivo Intra-Articular Antibiotic Concentrations at 24 Hours After TKA Fall Below the Minimum Inhibitory Concentration for Most Bacteria: A Randomized Study of Commercially Available Bone Cement.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) to help reduce the risk of infection after primary total knee arthroplasty (TKA) is controversial. There is a paucity of in vivo data on the elution characteristics of ALBC. We aimed to determine whether the antibiotic concentrations of 2 commercially available ALBCs met the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) for common infecting organisms. METHODS: Forty-five patients undergoing TKA were randomized to receive 1 of the following: bone cement without antibiotic (the negative control; n = 5), a commercially available formulation containing 1 g of tobramycin (n = 20), or a commercially available formulation containing 0.5 g of gentamicin (n = 20). Intra-articular drains were placed, and fluid was collected at 4 and 24 hours postoperatively. An automated immunoassay measuring antibiotic concentration was performed, and the results were compared against published MIC and MBEC thresholds. RESULTS: The ALBC treatment groups were predominantly of White (65%) or Black (32.5%) race and were 57.5% female and 42.4% male. The mean age (and standard deviation) was 72.6 ± 7.2 years in the gentamicin group and 67.6 ± 7.4 years in the tobramycin group. The mean antibiotic concentration in the tobramycin group was 55.1 ± 37.7 µg/mL at 4 hours and 19.5 ± 13.0 µg/mL at 24 hours, and the mean concentration in the gentamicin group was 38.4 ± 25.4 µg/mL at 4 hours and 17.7 ± 15.4 µg/mL at 24 hours. Time and antibiotic concentration had a negative linear correlation coefficient (r = -0.501). Most of the reference MIC levels were reached at 4 hours. However, at 24 hours, a considerable percentage of patients had concentrations below the MIC for many common pathogens, including Staphylococcus epidermidis (gentamicin: 65% to 100% of patients; tobramycin: 50% to 85%), methicillin-sensitive Staphylococcus aureus (gentamicin: 5% to 90%; tobramycin: 5% to 50%), methicillin-resistant S. aureus (gentamicin: 5% to 65%; tobramycin: 50%), Streptococcus species (gentamicin: 10% to 100%), and Cutibacterium acnes (gentamicin: 10% to 65%; tobramycin: 100%). The aforementioned ranges reflect variation in the MIC among different strains of each organism. Gentamicin concentrations reached MBEC threshold values at 4 hours only for the least virulent strains of S. aureus and Escherichia coli. Tobramycin concentrations did not reach the MBEC threshold for any of the bacteria at either time point. CONCLUSIONS: The elution of antibiotics from commercially available ALBC decreased rapidly following TKA, and only at 4 hours postoperatively did the mean antibiotic concentrations exceed the MIC for most of the pathogens. Use of commercially available ALBC may not provide substantial antimicrobial coverage following TKA. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Immune responses and severe dengue: what have we learned?

PURPOSE OF REVIEW: With the marked rise in dengue globally, developing well tolerated and effective vaccines and therapeutics is becoming more important. Here we discuss the recent developments in the understanding of immune mechanisms that lead to severe dengue and the learnings from the past, that can help us to find therapeutic targets, prognostic markers, and vaccines to prevent development of severe disease. RECENT FINDINGS: The extent and duration of viraemia often appears to be associated with clinical disease severity but with some variability. However, there also appear to be significant differences in the kinetics of viraemia and nonstructural protein 1 (NS1) antigenemia and pathogenicity between different serotypes and genotypes of the DENV. These differences may have significant implications for development of treatments and in inducing robust immunity through dengue vaccines. Although generally higher levels of neutralizing antibodies are thought to protect against infection and severe disease, there have been exceptions and the specificity, breadth and functionality of the antibody responses are likely to be important. SUMMARY: Although there have been many advances in our understanding of dengue pathogenesis, viral and host factors associated with occurrence of severe dengue, vascular leak and the immune correlates of protection remain poorly understood.

Fatality Rates After Infection With the Omicron Variant (B.1.1.529): How Deadly has it been? A Systematic Review and Meta-Analysis.

Background: Since late 2019, the global community has been gripped by the uncertainty surrounding the SARS-CoV-2 pandemic. In November 2021, the emergence of the Omicron variant in South Africa added a new dimension. This study aims to assess the disease's severity and determine the extent to which vaccinations contribute to reducing mortality rates. Methods: A systematic review and meta-analysis of the epidemiological implications of the omicron variant of SARS-CoV-2 were performed, incorporating an analysis of articles from November 2021that address mortality rates. Results: The analysis incorporated data from 3,214,869 patients infected with omicron, as presented in 270 articles. A total of 6,782 deaths from the virus were recorded (0.21%). In the analysed articles, the pooled mortality rate was 0.003 and the pooled in-house mortality rate was 0.036. Vaccination is an effective step in preventing death (odds ratio: 0.391, p < 0.01). Conclusion: The mortality rates for the omicron variant are lower than for the preceding delta variant. mRNA vaccination affords secure and effective protection against severe disease and death from omicron.