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Healthcare Professionals Working in Schools (HPWS) are responsible for providing health services to students and play a role in providing education to prevent illnesses, including tickborne diseases (TBD). Providing TBD education to children has been shown to increase prevention behaviors and knowledge of TBD symptoms, but little is known regarding the current state of TBD awareness among HPWS. In spring 2019 we conducted a cross-sectional knowledge, attitudes, and practices (KAP) survey of HPWS in two states with a high incidence of Lyme disease (LD) to inform design of TBD prevention programs. The survey queried general knowledge of TBDs, school practices regarding TBDs, and availability of TBD resources. Overall, higher confidence, experience, risk perception, prior training on TBD, and more years employed as a HPWS were independently associated with knowledge of LD transmission, symptoms, and correct tick removal practices. State and local health departments should consider prioritizing engagement with HPWS to provide educational opportunities about tickborne diseases.

Bartonella quintana is a small, facultatively intracellular, gram-negative bacillus that is transmitted to humans through the feces of an infected human body louse (Pediculus humanus corporis) (1). B. quintana infection [...]

Lyme disease (LD) is the most reported vector-borne disease in the United States (1). In separate efforts designed to better measure the burden of disease in the United States, we [...]

Bartonella quintana is a pathogenic bacterium carried and transmitted to humans by the body louse, Pediculus humanus humanus. Clinical manifestations of disease are relapsing fever, bacillary angiomatosis, chronic bacteremia, and [...]

Bartonella quintana infection can cause severe disease that includes clinical manifestations such as endocarditis, chronic bacteremia, and vasoproliferative lesions of the skin and viscera. B. quintana bacteria is transmitted by the human body louse (Pediculus humanus corporis) and is associated with homelessness and limited access to hygienic services. We report B. quintana infection in 2 kidney transplant recipients in the United States from an organ donor who was experiencing homelessness. One infection manifested atypically, and the other was minimally symptomatic; with rapid detection, both recipients received timely treatment and recovered. B. quintana was identified retrospectively in an archived donor hematoma specimen, confirming the transmission link. Information about the organ donor’s housing status was critical to this investigation. Evaluation for B. quintana infection should be considered for solid organ transplant recipients who receive organs from donors with a history of homelessness or of body lice infestation.

Abstract Background Commercial insurance claims data are a stable and consistent source of information on Lyme disease diagnoses in the United States and can contribute to our understanding of overall disease burden and the tracking of epidemiological trends. Algorithms consisting of diagnosis codes and antimicrobial treatment information have been used to identify Lyme disease diagnoses in claims data, but there might be opportunity to improve their accuracy. Methods We developed three modified versions of our existing claims-based Lyme disease algorithm; each reflected refined criteria regarding antimicrobials prescribed and/or maximum days between diagnosis code and qualifying prescription claim. We applied each to a large national commercial claims database to identify Lyme disease diagnoses during 2016–2019. We then compared characteristics of Lyme disease diagnoses identified by each of the modified algorithms to those identified by our original algorithm to assess differences from expected trends in demographics, seasonality, and geography. Results Observed differences in characteristics of patients with diagnoses identified by the three modified algorithms and our original algorithm were minimal, and differences in age and sex, in particular, were small enough that they could have been due to chance. However, one modified algorithm resulted in proportionally more diagnoses in men, during peak summer months, and in high-incidence jurisdictions, more closely reflecting epidemiological trends documented through public health surveillance. This algorithm limited treatment to only first-line recommended antimicrobials and shortened the timeframe between a Lyme disease diagnosis code and qualifying prescription claim. Conclusions As compared to our original algorithm, a modified algorithm that limits the antimicrobials prescribed and shortens the timeframe between a diagnosis code and a qualifying prescription claim might more accurately identify Lyme disease diagnoses when utilizing insurance claims data for supplementary, routine identification and monitoring of Lyme disease diagnoses.

Abstract Background Satisfaction with birth and healthcare provider experiences have long-term effects for maternal health. Research has shown that mothers who report more trust, respect, and self-efficacy in their relationship with their healthcare providers are more likely to report positive birthing experiences. Further, individuals with obesity, including pregnant mothers, are more likely to experience weight-related stigma from healthcare providers which may negatively impact satisfaction with this relationship. Thus, the current study examines maternal pre-pregnancy body mass index (BMI) as a moderator between birth and provider satisfaction. Methods A sample of 94 women (ages 16–38) were recruited during pregnancy. Participants completed surveys about their satisfaction with their birth experience, provider satisfaction, height, weight, and demographics including age and education. A moderation analysis was used to examine pre-pregnancy BMI as a moderator between birth and provider satisfaction. Results Results show that provider satisfaction is positively associated with birth satisfaction among mothers with moderate (overweight) to high (obese) pre-pregnancy BMI scores in our sample. Conclusions Findings suggest that strengthening the patient-provider relationship may promote satisfaction with birth experiences.

Abstract We present a comprehensive integrative taxonomic review of Callosciurus caniceps and Tamiops mcclellandii as they are currently defined. This review combines published molecular evidence, craniodental morphometrics, pelage and bacular variation, evaluations of potential hybrid zones using museum specimens and citizen science photographs, and, for C. caniceps, bioacoustic evidence. Our findings lead to the recognition of two species that had been lost in synonymy and highlight future perspectives on species delimitation in Sciuridae. By comparing phenotypic differentiation across climatic and vegetation transitions and contextualizing our results with the evolutionary history of our study systems, we provide insights into distribution, ecogeographical patterns, and speciation drivers in Southeast Asian vertebrates.

Beavers (Castor canadensis) have not been adequately included in critical zone research, yet they can affect multiple critical zone processes across the terrestrial-aquatic interface of river corridors. River corridors (RC) provide a disproportionate amount of ecosystem services. Over time, beaver activity, including submersion of woody vegetation, burrowing, dam building, and abandonment, can impact critical zone processes in the river corridor by influencing landscape evolution, biodiversity, geomorphology, hydrology, primary productivity, and biogeochemical cycling. In particular, they can effectively restore degraded riparian areas and improve water quality and quantity, causing implications for many important ecosystem services. Beaver-mediated river corridor processes in the context of a changing climate require investigation to determine how both river corridor function and critical zone processes will shift in the future. Recent calls to advance river corridor research by leveraging a critical zone perspective can be strengthened through the explicit incorporation of animals, such as beavers, into research projects over space and time. This article illustrates how beavers modify the critical zone across different spatiotemporal scales, presents research opportunities to elucidate the role of beavers in influencing Western U.S. ecosystems, and, more broadly, demonstrates the importance of integrating animals into critical zone science.

Study Region: This study focuses on the Cape Fear and Tar-Pamlico watersheds in North Carolina, which are characterized by diverse hydrological conditions, varied land use, soil types, and hydrological characteristics. Study Focus: The primary goal of this study is to examine the combined effects of three satellite precipitation products (SPPs) — ERA-5, gridMET, and GPM IMERG — along with three autocalibration techniques — DDS, GLUE, and LHS — on SWAT+ river flow predictions. Flow accuracy was assessed using three evaluation metrics: NSE, KGE, and R². New Hydrological Insights for the Region: Key findings revealed that five SWAT+ parameters (cn2, revap_co, flo_min, revap_min, and awc) were consistently sensitive across all SPPs and watersheds, with rainfall products exerting a greater influence on simulated river flow than optimization techniques. Among the SPPs, GPM IMERG performed the best, followed by ERA-5 and gridMET, while NSE was more responsive to changes in SPPs and calibration methods than KGE and R². For the Cape Fear and Tar-Pamlico watersheds, the study highlighted SWAT+ 's challenges in predicting base flow for groundwater-driven systems and demonstrated the potential of optimization techniques to improve flow simulations despite poor satellite-gauge rainfall correlation. The combination of the GPM IMERG dataset and the GLUE method proved most effective, offering valuable guidance for selecting optimal datasets and methods to enhance prediction accuracy in complex watersheds.

ObjectivesThis scoping review examines the evidence and knowledge gaps regarding the effectiveness of digital early childhood parenting interventions in Low- and Middle-Income Countries (LMICs).MethodsUsing PRISMA-ScR and PICOS frameworks, we systematically reviewed studies published since 2010 from four databases, focusing on the impact of digital parenting interventions on Early Childhood Development and parent-level outcomes.ResultsOf 1,399 studies identified, 13 met inclusion criteria, evaluating digital interventions for parents of children aged 0–5 years. These interventions included digital-only and hybrid approaches, leveraging technologies for tasks such as sharing health and ECD information, reminders, group chats, or screening. Among ECD studies, three of four with parent-reported outcomes found positive effects, but none of three using direct assessments did. Parent-level outcomes, such as mental health and parenting behaviors, showed consistent positive impacts.ConclusionDigital parenting interventions are feasible in LMICs but face challenges in implementation and reaching vulnerable families. Most studies are small-scale with variable designs and outcomes. Rigorous, high-quality studies are needed to establish effectiveness and optimize implementation strategies before these programs are deployed at scale.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

BackgroundThe incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA has not been previously reported.MethodsTrained thoracic radiologists evaluated 13 944 cardiac computed tomography scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study participants >45 years of age from 2000 to 2012. Five percent of the scans were re-read by the same or a different observer in a blinded fashion. After exclusion of participants with ILA at baseline, incidence rates and incidence rate ratios for ILA and fibrotic ILA were calculated.ResultsThe intra-reader agreement of ILA was 92.0% (Gwet's AC1 0.912, intraclass correlation coefficient (ICC) 0.982) and the inter-reader agreement of ILA was 83.5% (Gwet's AC1 0.814, ICC 0.969). Incidence of ILA and fibrotic ILA was estimated to be 13.1 and 3.5 cases per 1000 person-years, respectively. In multivariable analyses, age (hazard ratio (HR) 1.06 (95% CI 1.05-1.08); p

Although chimeric antigen receptor (CAR) T cell therapy has revolutionized type B cancer treatment, efficacy remains limited in various lymphomas and solid tumors. Reinforcing conventional CAR-T cells to release cytokines can improve their efficacy but also increase safety concerns. Several strategies have been developed to regulate their secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators. However, these chimeric proteins can disrupt the normal physiology of T cells. Here, we present the first transactivator-free anti-CD19 CAR-T cells able to control IL-18 expression (iTRUCK19.18) under ultra-low doses of doxycycline and without altering cellular fitness. Interestingly, IL-18 secretion requires T cell activation in addition to doxycycline, allowing the external regulation of CAR-T cell potency. This effect was translated into an increased CAR-T cell antitumor activity against aggressive hematologic and solid tumor models. In a clinically relevant context, we generated patient-derived iTRUCK19.18 cells capable of eradicating primary B cells tumors in a doxycycline-dependent manner. Furthermore, IL-18-releasing CAR-T cells polarized pro-tumoral macrophages toward an antitumoral phenotype, suggesting potential for modulating the tumor microenvironment. In summary, we showed that our platform can generate exogenously controlled CAR-T cells with enhanced potency and in the absence of transactivators.

Tick-borne diseases are commonly reported in the United States, but frequency of tick bites and care-seeking behaviors following tick bites are poorly understood. We used nationally representative survey data to describe the frequency of tick bites among people living in the United States and how often, where, and why care-seeking associated with tick bites occurs. We found that over 31 million people (nearly 1 in 10) living in the United States might experience a tick bite each year and highlight regional trends in associated care-seeking behaviors. These findings emphasize the need for effective tick bite prevention education and regionally tailored healthcare provider recommendations for management of tick-borne diseases.

There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC50 in the region near the perfusion channel versus the region far from the channel. We compared behaviour of organoids in this platform to two commonly used PDO culture models: organoids in media and organoids in a static (no perfusion) hydrogel. The bioreactor IC50 values were significantly higher than IC50 values for organoids cultured in media whereas only the IC50 for organoids far from the channel were significantly different than organoids cultured in the static hydrogel condition. Using finite element simulations, we showed that the total dose delivered, calculated using area under the curve (AUC) was similar between platforms, however normalized viability was lower for the organoid in media condition than in the static gel and bioreactor. Our results highlight the utility of our multi-well bioreactor for studying organoid response to chemical gradients and demonstrate that comparing drug response across these different platforms is nontrivial.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

Tickborne diseases are an increasing public health problem, accounting for [approximately equal to] 75% of reported vector-borne illnesses in the United States (1-3). Continued discovery of new tickborne pathogens in [...]

The blood–brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier. This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE). Using an in vivo rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared. Equivalent waveforms were designed for direct comparison between the two pulsing schemes, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation. While B-SWE exhibited heightened neuromuscular contractions when compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that a reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions. Repair kinetics indicated faster closure post B-SWE-induced BBB disruption when compared to equivalent H-FIRE protocols, emphasizing B-SWE's transient and controllable nature. Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE. B-SWE presents a promising avenue for tailored BBB disruption with minimal tissue ablation, offering a nuanced approach for glioblastoma treatment and beyond.

Abstract Background The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. Methods We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. Discussion We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. Trial registration ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Background: Carpal Tunnel Syndrome (CTS) is associated with a significant personal and societal burden. Evaluating access to care can identify barriers, limitations, and disparities in the delivery of healthcare services in this population. The purpose of this study was to evaluate access to overall healthcare and healthcare utilization among patients with CTS. Methods: This is a retrospective cohort study conducted with the All of Us database. Patients diagnosed with CTS that completed the access to care survey were included and matched to a control group. The primary outcomes were access to care across 4 domains: (1) delayed care, (2) could not afford care, (3) skipped medications, and (4) over 1 year since seeing provider. Secondary analysis was then performed to identify patient-specific factors associated with reduced access to care. Results: In total, 7649 patients with CTS were included and control matched to 7649 patients without CTS. In the CTS group, 33.7% (n = 2577) had delayed care, 30.4% (n = 2323) could not afford care, 15.4% (n = 1180) skipped medications, and 1.6% (n = 123) had not seen a provider in more than 1 year. Within the CTS cohort, low-income, worse physical health, and worse mental health were associated with poor access to care. Conclusion: Patients experience notable challenges with delayed care, affordability of care, and medication adherence regardless of having a diagnosis of CTS. Targeted interventions on modifiable risk factors such as low income, poor mental health, and poor physical health are important opportunities to improve access to care in this population.