Countering vaccine misinformation: Designing a learning resource for healthcare workers in eight countries.

In response to the pervasive challenges posed by online health misinformation, our objective was to develop a training program aimed at enhancing the skills and confidence of healthcare workers in recognizing and effectively responding to misinformation, with a particular focus on vaccinations. This article discusses the design of a training program aimed at equipping healthcare workers with the skills to combat health misinformation, offering theoretical foundations for integrating evidence-based strategies into problem-based learning to help learners retain and apply information, and also shares examples and insights gained from its application across diverse learner groups. The training curriculum integrates evidence-based misinformation intervention strategies, learner engagement strategies and draws from authentic scenarios across diverse cultural contexts. The trainings were administered from January through July 2023 to 287 participants across eight countries (Cameroon, Guyana, India, Kenya, Mozambique, Nigeria, Philippines, and the United States) in English, French, Spanish, and Portuguese. Throughout the implementation of the training, a key emphasis was placed on a learner-driven approach that fostered real-world application. Participants engaged in role-playing exercises and problem-solving sessions, enabling them to practice their newfound skills in a controlled setting. Our findings contribute to the literature of participatory, problem-based learning for healthcare professionals and vaccine communication and misinformation response, and can serve as a resource for practitioners implementing similar trainings.

Understanding Kenyan policymakers' perspectives about the introduction of new maternal vaccines.

New vaccine policy adoption is a complex process, especially in low-and-middle-income countries (LMICs), requiring country policymakers to navigate challenges such as competing priorities, human and financial resource constraints, and limited logistical capacity. Since the Expanded Programme on Immunization's (EPI) beginning, most new vaccine introductions under this structure have not been aimed at adult populations. The majority of adult vaccines offered under the EPI are not typically tested among and tailored for pregnant persons, except those that are specifically recommended for pregnancy. Given that new maternal vaccines, including RSV and GBS vaccines, are on the horizon, it is important to understand what barriers may arise during the policy development and vaccine introduction process. In this study, we sought to understand information needs among maternal immunization policymakers and decision-makers in Kenya for new vaccine maternal policy adoption through in-depth interviews with 20 participants in Nakuru and Mombasa counties in Kenya. Results were mapped to an adapted version of an established framework by Levine et al., (2010) focused on new vaccine introduction in LMICs. Participants reported that the policy process for new maternal vaccine introduction requires substantial evidence as well as coordination among diverse stakeholders. Importantly, our findings suggest that the process for new maternal vaccines does not end with the adoption of a new policy, as intended recipients and various actors can determine the success of a vaccine program. Previous shortcomings, in Kenya, and globally during HPV vaccine introduction show the need to allocate adequate resources in education of communities given the sensitive target group. With maternal vaccines targeting a sensitive group - pregnant persons- in the pipeline, we are at an opportune time to understand how to ensure successful vaccine introduction with optimal acceptance and uptake, while also addressing vaccine hesitancy to increase population benefit.

Patient experiences with telehealth treatment for opioid use disorder in Alabama.

INTRODUCTION: Telehealth-only provision of buprenorphine for the treatment of opioid use disorder (OUD) was first made possible during the COVID-19 pandemic. However, Alabama instituted a law in July 2022 that mandated an annual in-person visit in order to receive this treatment. In July 2023, our usually telehealth-only group established a temporary clinic in Birmingham to meet this requirement. METHODS: The study administered a survey instrument to patients at the time of clinic check-in. RESULTS: 158 of 160 (98.8 %) patients completed the survey. Mean distance traveled was 86.4 (standard deviation (SD) 53.7) miles; time required for travel was mean 1.6 (SD 1.0) hours. Twenty-five patients (15.8 %) reported needing to find childcare to attend the visit and 40 patients (25.3 %) reported missing work to attend. Patients disagreed (median 2 on 1-5 Likert scale, interquartile range (IQR) <1-3>) that it is important to see their provider in-person, that seeing their provider in-person improves care or improves their ability to succeed in treatment, and that they have other OUD treatment resources in their community. Patients strongly agreed (median 5, IQR <5-5>) that OUD can be treated by telehealth without the need for an in-person visit. CONCLUSIONS: An annual in-person visits requirement to receive telehealth OUD services imposed a significant burden on patients, was not desired by patients, and may be associated with harm.

Distinct pathway for evolution of enhanced receptor binding and cell entry in SARS-like bat coronaviruses.

Understanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from divergent bat CoVs to investigate their cell entry mechanisms. Unexpectedly, the successful recovery of rVSVs bearing the spike from SHC014, a SARS-like bat CoV, was associated with the acquisition of a novel substitution in the S2 fusion peptide-proximal region (FPPR). This substitution enhanced viral entry in both VSV and coronavirus contexts by increasing the availability of the spike receptor-binding domain to recognize its cellular receptor, ACE2. A second substitution in the spike N-terminal domain, uncovered through forward-genetic selection, interacted epistatically with the FPPR substitution to synergistically enhance spike:ACE2 interaction and viral entry. Our findings identify genetic pathways for adaptation by bat CoVs during spillover and host-to-host transmission, fitness trade-offs inherent to these pathways, and potential Achilles' heels that could be targeted with countermeasures.

The Emerging Landscape of Social Media Influencers in Public Health Collaborations: A Scoping Review.

Social media content creators or "influencers" are an increasingly influential voice in the public discourse generally, including global perceptions and practices related to health. In response, public health entities are increasingly embracing social media influencers (SMIs) as potential health promotion collaborators. Despite burgeoning interest in the potential of these partnerships, research evaluating this strategy remains limited. To address this gap, we conducted a scoping review to characterize and describe the current landscape of health promotion collaborations with SMIs with a focus on current practices. A search of six electronic databases (PubMed, SCOPUS, Communication & Mass Media Complete, CINAHL Plus, Web of Science, and APA PsycINFO) revealed wide-ranging and inconsistent approaches to these partnerships, including their optimal practices, data reported, and their evaluation criteria. Among the 658 articles initially identified, 15 publications met our inclusion criteria, spanning 7 countries, 8 social media platforms, 11 distinct health topics, and 21 different outcome measures. Basic information necessary for comparing across interventions was often lacking. We noted a lack of consensus on what constitutes an SMI with 53% of included studies lacking any definition or criteria. Although SMIs offer substantial promise as an emerging opportunity for health promotion, particularly for populations that may be otherwise difficult to identify or reach, this review highlights how the current lack of standardized methodologies and metrics prevents meaningful comparisons between collaborations and evaluations of their effectiveness. Based on these findings, we propose four key criteria to aid practitioners in the implementation and evaluation of SMI collaborations.

Naloxone prescription fills and use by patients treated for opioid use disorder by telehealth.

Background: It is unknown how many people in treatment for opioid use disorder (OUD) have naloxone, use naloxone, and what their perceptions and barriers to obtaining it are. Methods: This was a survey of patients treated in a large telehealth OUD program. Between December 6, 2023 and January 6, 2024, all patients who had access to the program's phone app (n=17,899 individuals, of whom 12,887 were in active treatment), were invited to complete an anonymous online survey. Results: There were 701 individuals who completed the survey. Nearly all patients (n=693, 99%) knew what naloxone is, and the majority (n=601, 86%) knew how to administer it. A quarter of these patients (n=177, 25%) reported either having naloxone used on themselves or using it on someone else. 161 patients (23%) reported taking a naloxone training course. Of patients who recalled receiving a prescription, 72% (n=382) filled the prescription, and 85% (n=321) reported that insurance paid for all or part of it. If filled, the naloxone was reported as used by 30 (8%) patients. If not filled, reasons were: already had it (n=55, 37%), did not think it was needed (n=54, 37%) or too expensive (n=36, 23%). Patients who reported knowing how to administer naloxone (OR 2.63 (95% CI 1.35-5.00) were more likely to fill the prescription. Conclusions: Patients prescribed naloxone in a telehealth treatment program filled the prescription 72% of the time, and when it was filled, 8% used the naloxone. Education and cost policy changes may reduce barriers to obtaining naloxone.

A VHH single-domain platform enabling discovery and development of monospecific antibodies and modular neutralizing bispecifics against SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, escape coronavirus disease 2019 therapeutics and vaccines, and jeopardize public health. To combat SARS-CoV-2 antigenic escape, we developed a rapid, high-throughput pipeline to discover monospecific VHH antibodies and iteratively develop VHH-Fc-VHH bispecifics capable of neutralizing emerging SARS-CoV-2 variants. By panning VHH single-domain phage libraries against ancestral or beta spike proteins, we discovered high-affinity VHH antibodies with unique target epitopes. Combining two VHHs into a tetravalent bispecific construct conferred broad neutralization activity against multiple variants and was more resistant to antigenic escape than the monospecific antibody alone. Following the rise of the Omicron variant, a VHH in the original bispecific construct was replaced with another VHH discovered against the Omicron BA.1 receptor binding domain; the resulting bispecific exhibited neutralization against both BA.1 and BA.5 sublineage variants. A heavy chain-only tetravalent VHH-Fc-VHH bispecific platform derived from humanized synthetic libraries held a myriad of unique advantages: (i) synthetic preconstructed libraries minimized risk of liabilities and maximized discovery speed, (ii) VHH scaffolds allowed for a modular "plug-and-play" format that could be rapidly iterated upon as variants of concern arose, (iii) natural dimerization of single VHH-Fc-VHH polypeptides allowed for straightforward bispecific production and purification methods, and (iv) multivalent approaches enhanced avidity boosting effects and neutralization potency, and conferred more robust resistance to antigenic escape than monovalent approaches against specific variants. This iterative platform of rapid VHH discovery combined with modular bispecific design holds promise for long-term viral control efforts.

In vivo human knee varus-valgus loading apparatus for analysis of MRI-based intratissue strain and relaxometry.

The diagnosis of early-stage osteoarthritis remains as an unmet challenge in medicine and a roadblock to evaluating the efficacy of disease-modifying treatments. Recent studies demonstrate that unique patterns of intratissue cartilage deformation under cyclic loading can serve as potential biomarkers to detect early disease pathogenesis. However, a workflow to obtain deformation, strain maps, and quantitative MRI metrics due to the loading of articular cartilage in vivo has not been fully developed. In this study, we characterize and demonstrate an apparatus that is capable of applying a varus-valgus load to the human knee in vivo within an MRI environment to enable the measurement of cartilage structure and mechanical function. The apparatus was first tested in a lab environment, then the functionality and utility of the apparatus were examined during varus loading in a clinical 3T MRI system for human imaging. We found that the device enables quantitative MRI metrics for biomechanics and relaxometry data acquisition during joint loading leading to compression of the medial knee compartment. Integration with spiral DENSE MRI during cyclic loading provided time-dependent displacement and strain maps within the tibiofemoral cartilage. The results from these procedures demonstrate that the performance of this loading apparatus meets the design criteria and enables a simple and practical workflow for future studies of clinical cohorts, and the identification and validation of imaging-based biomechanical biomarkers.

Modeling the impact of decreasing waiting period length for Medicaid sterilization: A multi-site cohort study.

OBJECTIVE: To evaluate the impact of length of the Medicaid sterilization waiting period and postpartum permanent contraception fulfillment. STUDY DESIGN: Simulations from a retrospective cohort study estimating the potential increase in permanent contraception within 365 days of delivery. RESULTS: In our sample of 2076 patients, 61% achieved permanent contraception with the current waiting period of 30 days. With the waiting period hypothetically reduced to 15, 3, 1, and 0 days, 62.9%, 63.7%, 64.5%, and 75% patients, respectively, would have achieved permanent contraception. CONCLUSIONS: As potential Medicaid sterilization policy revisions are considered, understanding the impact on fulfillment rates is critical.

Ongoing contraceptive goals of patients who did not achieve desired postpartum permanent contraception prior to hospital discharge.

OBJECTIVE: To evaluate reasons for non-fulfillment and ongoing contraceptive plans of patients who desired but did not receive inpatient postpartum permanent contraception (PC). STUDY DESIGN: Multi-site retrospective cohort study of 1254 patients with unfulfilled inpatient postpartum PC. We analyzed the reason for PC non-fulfillment, documented contraceptive plan, and method prescription or provision at hospital discharge, six-weeks, and one-year postpartum. RESULTS: In our cohort, 44.3% of patients with unfulfilled inpatient PC did not receive any highly- or moderately-effective contraception within one year postpartum. CONCLUSIONS: Removing barriers to PC fulfillment as well as contraceptive counseling that acknowledges these barriers is imperative.

Association between potentially traumatic birthing experience and worsening postpartum depression or anxiety trajectories among participants in perinatal collaborative care model.

BACKGROUND: Having a potentially traumatic birth experience (PTBE) is a known risk factor for postpartum depression (PPD) and postpartum anxiety (PPA). PTBE-related PPA or PPD can peak long after six weeks postpartum, when typical screening for PPD and PPA typically occurs, leaving many of these individuals disconnected from care. Collaborative care models (CCMs) have been shown to reduce PPD and PPA via collaboration between care managers, obstetric clinicians, and mental health professionals. Whether participating in a CCM mitigates the risk of worsening PPD or PPA after PTBE is unknown. OBJECTIVE: To examine trajectories of PPD and PPA among those who experienced a PTBE and participated in a CCM. STUDY DESIGN: This secondary analysis of a prospective cohort study included people enrolled in COMPASS, a CCM program embedded within all Northwestern Medicine prenatal clinics. All pregnant or postpartum people with a history of a mental health conditions or current mental health symptoms during pregnancy or within a year postpartum are eligible for COMPASS referral. Those who enroll in COMPASS are screened every two to four weeks for depression and anxiety symptoms using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. For this secondary analysis, COMPASS participants were stratified into two groups based on whether they had a PTBE, defined as postpartum hemorrhage, maternal intensive care unit (ICU) admission, or preterm birth <35 weeks (the gestational age cut-off for required Neonatal Intensive Care Unit (NICU) admission at this medical center). PTBE was evaluated as a composite and as its individual subcomponents. The primary outcomes were worsening trajectories for PPD or PPA, defined by a score increase of ≥1 standard deviation on the PHQ-9 or GAD-7, respectively, on at least two assessments for up to one year postpartum. A propensity score was used in multivariable models to control for covariates that significantly differed in bivariable analysis. RESULTS: Among 2,312 COMPASS participants, 413 (17.9%) had PTBE. Compared to those without a PTBE, those with PTBE were more likely to have a pregnancy conceived via IVF, public insurance, or be diagnosed with preexisting diabetes, preexisting hypertension, or obesity. Among 736 and 282 participants with at least two PPD and PPA assessments, 65 (2.8%) and 27 (1.2%) had worsening PPD or PPA trajectories, respectively. After using propensity scores to control for differences identified between groups, PTBE was not associated with worsening trajectories for PPD [aOR 0.92 (95% CI 0.36, 2.38)] or PPA [(aOR 0.64 (95% CI 0.12, 3.26)]. There was no association between individual conditions within the PTBE composite and worsening PPD or PPA trajectories. CONCLUSIONS: Among those enrolled in COMPASS, worsening PPD or PPA trajectories were uncommon, and PTBE were not associated with worsening trajectories. Given the abundance of literature suggesting that PTBE are associated with worse PPD and PPA symptoms, these findings suggest that enrollment in a CCM may be associated with mitigation of the negative impact of PTBE.

Proactive Coping in Early Pregnancy and Adverse Pregnancy Outcomes.

Objective: Outside of pregnancy, proactive coping has been associated with both mental and physical well-being and with improved quality of life in chronic disease, but its effects in pregnancy are understudied. Our objective was to evaluate whether early pregnancy proactive coping was associated with adverse perinatal outcomes. Study Design: This was a planned secondary analysis of nulliparous pregnant people recruited from a tertiary care center. Participants completed a validated assessment of proactive coping (Proactive Coping Scale) at 8-20 weeks and were followed longitudinally through delivery. Detailed pregnancy and delivery data were collected by trained research personnel. The primary outcome was a composite of adverse perinatal outcomes including unplanned cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy. Secondary analyses included individual perinatal composite components and a neonatal morbidity composite measure. Multivariate regression compared adverse perinatal outcomes by Proactive Coping Scale quartile, controlling for a priori confounders. Results: Of the 281 parturients, the median Proactive Coping Scale score was 45.0 (range 25-55), and 47% experienced an adverse perinatal outcome. After adjusting for confounders, those in the lowest Proactive Coping Scale quartile had 2.2 times higher odds of experiencing an adverse perinatal outcome compared to those in the highest Proactive Coping Scale quartile. There were no differences in odds of the individual composite components or the adverse neonatal outcome. Conclusion: Lower early pregnancy proactive coping scores are associated with significant increase in adverse perinatal outcomes. Interventions that target improving proactive coping may be a novel mechanism for reducing perinatal morbidity.

Proactive coping is the process of preparing for a stressor or goal, which has been studied in the context of chronic disease. We sought to understand how proactive coping relates to pregnancy outcomes. Our results indicated that higher proactive coping scores were associated with lower risk of adverse pregnancy outcomes. Therefore, interventions to increase proactive coping may have a role in reducing adverse pregnancy outcomes.

Fulfillment of Permanent Contraception among Patients with Cesarean Delivery in a Multi-Site Cohort.

OBJECTIVES: This study aimed to assess the association between insurance type and permanent contraception fulfillment among those with cesarean deliveries. Additionally, we sought to examine modification by the scheduled status of the cesarean. STUDY DESIGN: We used data from a multi-site cohort study of patients who delivered in 2018-2019 at Northwestern Memorial Hospital in Illinois, MetroHealth Medical System in Ohio, or University of Alabama at Birmingham in Alabama. All patients had permanent contraception as their contraceptive plan in their medical chart during delivery hospitalization. We used logistic regression to model the association between insurance type, scheduled status of cesarean and permanent contraception fulfillment by hospital discharge. The scheduled status of cesarean delivery was examined as an effect modifier. RESULTS: Compared to patients with private insurance, those with Medicaid were less likely to have their desired permanent contraception procedure fulfilled by hospital discharge (89.3% vs. 96.8%, p < 0.001). After adjusting for covariates, patients with Medicaid had a lower odds of permanent contraception fulfillment by hospital discharge (OR: 0.41; 95% CI: 0.21, 0.77). This association was stronger among those who had unscheduled cesarean deliveries (OR: 0.29; 95% CI: 0.12, 0.74) than those with scheduled cesarean deliveries (OR: 0.77; 95% CI: 0.32, 1.88). CONCLUSIONS FOR PRACTICE: Compared to patients with private insurance undergoing a cesarean delivery, those with Medicaid insurance were less likely to have their desired permanent contraception fulfilled. Physicians and hospitals must examine their practices surrounding Medicaid forms to ensure that patients have valid consent forms available at the time of delivery.

Neighbourhood socioeconomic position, prenatal care and fulfilment of postpartum permanent contraception: Findings from a multisite cohort study.

Introduction: Research suggests neighbourhood socioeconomic vulnerability is negatively associated with women's likelihood of receiving adequate prenatal care and achieving desired postpartum permanent contraception. Receiving adequate prenatal care is linked to a greater likelihood of achieving desired permanent contraception, and access to such care may be critical for women with Medicaid insurance given that the federally mandated Medicaid sterilization consent form must be signed at least 30 days before the procedure. We examined whether adequacy of prenatal care mediates the relationship between neighbourhood socioeconomic position and postpartum permanent contraception fulfilment, and examined moderation of relationships by insurance type. Methods: This secondary analysis of a retrospective cohort study examined 3012 Medicaid or privately insured individuals whose contraceptive plan at postpartum discharge was permanent contraception. Path analysis estimated relationships between neighbourhood socioeconomic position (economic hardship and inequality, financial strength and educational attainment) and permanent contraception fulfilment by hospital discharge, directly and indirectly through adequacy of prenatal care. Multigroup testing examined moderation by insurance type. Results: After adjusting for age, parity, weeks of gestation at delivery, mode of delivery, race, ethnicity, marital status and body mass index, having adequate prenatal care predicted achieving desired sterilization at discharge (ß = 0.065, 95% confidence interval [CI]: 0.011, 0.117). Living in neighbourhoods with less economic hardship (indirect effect -0.007, 95% CI: -0.015, -0.001), less financial strength (indirect effect -0.016, 95% CI: -0.030, -0.002) and greater educational attainment (indirect effect 0.012, 95% CI: 0.002, 0.023) predicted adequate prenatal care, in turn predicting achievement of permanent contraception by discharge. Insurance status conditioned some of these relationships. Conclusion: Contact with the healthcare system via prenatal care may be a mechanism by which neighbourhood socioeconomic disadvantage affects permanent contraception fulfilment, particularly for patients with Medicaid. To promote reproductive autonomy and healthcare equity, future inquiry and policy might closely examine how neighbourhood social and economic characteristics interact with Medicaid mandates.

The design and implementation of a multi-center, pragmatic, individual-level randomized controlled trial to evaluate Baby2Home, an mHealth intervention to support new parents.

BACKGROUND: Becoming a parent is a transformative experience requiring multiple transitions, including the need to navigate several components of health care, manage any mental health issues, and develop and sustain an approach to infant feeding. Baby2Home (B2H) is a digital intervention built on the collaborative care model (CCM) designed to support families during these transitions to parenthood. OBJECTIVES: We aim to investigate the effects of B2H on preventive healthcare utilization for the family unit and patient-reported outcomes (PROs) trajectories with a focus on mental health. We also aim to evaluate heterogeneity in treatment effects across social determinants of health including self-reported race and ethnicity and household income. We hypothesize that B2H will lead to optimized healthcare utilization, improved PROs trajectories, and reduced racial, ethnic, and income-based disparities in these outcomes as compared to usual care. METHODS: B2H is a multi-center, pragmatic, individual-level randomized controlled trial. We will enroll 640 families who will be randomized to: [1] B2H + usual care, or [2] usual care alone. Preventive healthcare utilization is self-reported and confirmed from medical records and includes attendance at the postpartum visit, contraception use, depression screening, vaccine uptake, well-baby visit attendance, and breastfeeding at 6 months. PROs trajectories will be analyzed after collection at 1 month, 2 months, 4 months, 6 months and 12 months. PROs include assessments of stress, depression, anxiety, self-efficacy and relationship health. IMPLICATIONS: If B2H proves effective, it would provide a scalable digital intervention to improve care for families throughout the transition to new parenthood.

MRI-derived Articular Cartilage Strains Predict Patient-Reported Outcomes Six Months Post Anterior Cruciate Ligament Reconstruction.

Key terms: Multicontrast and Multiparametric, Magnetic Resonance Imaging, Osteoarthritis, Functional Biomechanical Imaging, Knee Joint Degeneration What is known about the subject: dualMRI has been used to quantify strains in a healthy human population in vivo and in cartilage explant models. Previously, OA severity, as determined by histology, has been positively correlated to increased shear and transverse strains in cartilage explants. What this study adds to existing knowledge: This is the first in vivo use of dualMRI in a participant demographic post-ACL reconstruction and at risk for developing osteoarthritis. This study shows that dualMRI-derived strains are more significantly correlated with patient-reported outcomes than any MRI relaxometry metric. Background: Anterior cruciate ligament (ACL) injuries lead to an increased risk of osteoarthritis, characterized by altered cartilage tissue structure and function. Displacements under applied loading by magnetic resonance imaging (dualMRI) is a novel MRI technique that can be used to quantify mechanical strain in cartilage while undergoing a physiological load. Purpose: To determine if strains derived by dualMRI and relaxometry measures correlate with patient-reported outcomes at six months post unilateral ACL reconstruction. Study Design: Cohort study. Methods: Quantitative MRI (T2, T2*, T1ρ) measurements and transverse, axial, and shear strains were quantified in the medial articular tibiofemoral cartilage of 35 participants at six-months post unilateral ACL reconstruction. The relationships between patient-reported outcomes (WOMAC, KOOS, MARS) and all qMRI relaxation times were quantified using general linear mixed-effects models. A combined best-fit multicontrast MRI model was then developed using backwards regression to determine the patient features and MRI metrics that are most predictive of patient-reported outcome scores. Results: Higher femoral strains were significantly correlated with worse patient-reported functional outcomes. Femoral shear and transverse strains were positively correlated with six-month KOOS and WOMAC scores, after controlling for covariates. No relaxometry measures were correlated with patient-reported outcome scores. We identified the best-fit model for predicting WOMAC score using multiple MRI measures and patient-specific information, including sex, age, graft type, femoral transverse strain, femoral axial strain, and femoral shear strain. The best-fit model significantly predicted WOMAC score (p<0.001) better than any one individual MRI metric alone. When we regressed the model-predicted WOMAC scores against the patient-reported WOMAC scores, we found that our model achieved a goodness of fit exceeding 0.52. Conclusions: This work presents the first use of dualMRI in vivo in a cohort of participants at risk for developing osteoarthritis. Our results indicate that both shear and transverse strains are highly correlated with patient-reported outcome severity could serve as novel imaging biomarkers to predict the development of osteoarthritis.

Nurturing transformative local structures of multisectoral collaboration for primary health care: qualitative insights from select states in India.

BACKGROUND: Multisectoral collaboration is essential for advancing primary health care (PHC). In low- and middle-income countries (LMICs), limited institutional capacities, governance issues, and inadequate stakeholder engagement impede multisectoral collaboration. India faces similar challenges, especially at the meso-level (districts and subdistricts). Owing to its dependence on context, and insufficient evidence, understanding "How" to improve multisectoral collaboration remains challenging. This study aims to elicit specific recommendations to strengthen meso-level stewardship in India for multisectoral collaboration. The findings from this study may offer lessons for other LMICs. METHODS: Using purposive, maximum variation sampling, the study team conducted semi-structured interviews with 20 diverse participants, including policymakers, implementers, development agency representatives, and academics experienced in multisectoral initiatives. The interviews delved into participants' experiences, the current situation, enablers, and recommendations for enhancing stakeholder engagement and capacities at the meso-level for multisectoral collaboration. RESULTS: Context and power are critical elements to consider in fostering effective collaboration. Multisectoral collaboration was particularly successful in three distinct governance contexts: the social-democratic context as in Kerala, the social governance context in Chhattisgarh, and the public health governance context in Tamil Nadu. Adequate health system input and timely guidance instil confidence among local implementers to collaborate. While power plays a role through local leadership's influence in setting agendas, convening stakeholders, and ensuring accountability. To nurture transformative local leaders for collaboration, holistic, equity-driven, community-informed approaches are essential. The study participants proposed several concrete steps: at the state level, establish "central management units" for supervising local implementers and ensuring bottom-up feedback; at the district level, rationalise committees and assign deliverables to stakeholders; and at the block level, expand convergence structures and involve local self-governments. Development partners can support data-driven priority setting, but local implementers with contextual familiarity should develop decentralised plans collaboratively, articulating rationales, activities, and resources. Finally, innovative training programs are required at all levels, fostering humility, motivation, equity awareness, leadership, problem- solving, and data use proficiency. CONCLUSION: This study offers multiple solutions to enhance local implementers' engagement in multisectoral efforts, advocating for the development, piloting, and evaluation of innovative approaches such as the block convergence model, locally-led collaboration efforts, and novel training methods for local implementers.

Engineering the cellulolytic bacterium, Clostridium thermocellum, to co-utilize hemicellulose.

Consolidated bioprocessing (CBP) of lignocellulosic biomass holds promise to realize economic production of second-generation biofuels/chemicals, and Clostridium thermocellum is a leading candidate for CBP due to it being one of the fastest degraders of crystalline cellulose and lignocellulosic biomass. However, CBP by C. thermocellum is approached with co-cultures, because C. thermocellum does not utilize hemicellulose. When compared with a single-species fermentation, the co-culture system introduces unnecessary process complexity that may compromise process robustness. In this study, we engineered C. thermocellum to co-utilize hemicellulose without the need for co-culture. By evolving our previously engineered xylose-utilizing strain in xylose, an evolved clonal isolate (KJC19-9) was obtained and showed improved specific growth rate on xylose by ∼3-fold and displayed comparable growth to a minimally engineered strain grown on the bacteria's naturally preferred substrate, cellobiose. To enable full xylan deconstruction to xylose, we recombinantly expressed three different ß-xylosidase enzymes originating from Thermoanaerobacterium saccharolyticum into KJC19-9 and demonstrated growth on xylan with one of the enzymes. This recombinant strain was capable of co-utilizing cellulose and xylan simultaneously, and we integrated the ß-xylosidase gene into the KJC19-9 genome, creating the KJCBXint strain. The strain, KJC19-9, consumed monomeric xylose but accumulated xylobiose when grown on pretreated corn stover, whereas the final KJCBXint strain showed significantly greater deconstruction of xylan and xylobiose. This is the first reported C. thermocellum strain capable of degrading and assimilating hemicellulose polysaccharide while retaining its cellulolytic capabilities, unlocking significant potential for CBP in advancing the bioeconomy.