Long COVID Definitions and Models of Care : A Scoping Review.

BACKGROUND: Definitions of long COVID are evolving, and optimal models of care are uncertain. PURPOSE: To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models. DATA SOURCES: English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants. STUDY SELECTION: Publications describing long COVID definitions or models of care, supplemented by models described by key informants. DATA EXTRACTION: Data were extracted by one reviewer and verified for accuracy by another reviewer. DATA SYNTHESIS: Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score-based. Forty-nine long COVID care models were informed by 5 key principles: a core "lead" team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified. LIMITATIONS: Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models. CONCLUSION: Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.).

Investigating How the Properties of Electrospun Poly(lactic acid) Fibres Loaded with the Essential Oil Limonene Evolve over Time under Different Storage Conditions.

Essential oils have been identified as effective natural compounds to prevent bacterial infections and thus are widely proposed as bioactive agents for biomedical applications. Across the literature, various essential oils have been incorporated into electrospun fibres to produce materials with, among others, antibacterial, anti-inflammatory and antioxidant activity. However, limited research has been conducted so far on the effect of these chemical products on the physical characteristics of the resulting composite fibres for extended periods of time. Within this work, electrospun fibres of poly(lactic acid) (PLA) were loaded with the essential oil limonene, and the impact of storage conditions and duration (up to 12 weeks) on the thermal degradation, glass transition temperature and mechanical response of the fibrous mats were investigated. It was found that the concentration of the encapsulated limonene changed over time and thus the properties of the PLA-limonene fibres evolved, particularly in the first two weeks of storage (independently from storage conditions). The amount of limonene retained within the fibres, even 4 weeks after fibre generation, was effective to successfully inhibit the growth of model microorganisms Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The results of this work demonstrate the importance of evaluating physical properties during the ageing of electrospun fibres encapsulating essential oils, in order to predict performance modification when the composite fibres are used as constituents of medical devices.

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.

Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70-targeted allogeneic CAR T cells. SIGNIFICANCE: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.

Shifts in the genetic counseling workforce highlight a need for laboratory fieldwork experience for genetic counseling trainees.

As the genetic counseling workforce experiences an increase in genetic counselors (GCs) in non-direct patient care roles, it is essential that genetic counseling students are trained in these settings. The Accreditation Council for Genetic Counseling (ACGC) standards regarding laboratory exposure have evolved over time, but laboratory fieldwork experience continues to remain a suggestion for a diversified setting. As more trainees seek laboratory exposure and an increasing number of new graduates opt for laboratory positions, learning firsthand from GCs employed in this setting is a valuable experience that should be available to all trainees. Historically, laboratory educational offerings consisted of onsite rotations for students from local training programs focused on understanding diagnostic testing methodologies and shadowing GCs. Through the years, multiple laboratories have expanded their curriculums to expose students to variant interpretation and report writing, research, client services, marketing, and product development. Alongside the growth of laboratory rotation curriculum grew opportunities for remote rotations. Prior to the COVID-19 pandemic, GeneDx offered remote education options including both individualized rotations and a webinar series. These offerings expanded due to the pandemic coupled with increased demand and have positive implications for future trainees. The evolution of the rotation also included conscious efforts to incorporate diversity, equity, and inclusion into the curriculum, as well as to improved accessibility to laboratory rotations. Notably, there are inconsistencies in laboratory rotation curricula and requirements, and a standardized evaluation and definition of competencies are lacking. ACGC guidelines defining common core concepts required from laboratory rotations would help ensure students receive an equitable minimum skill set, regardless of training site. Stakeholders in GC education should collaborate to enhance the experiences of future trainees and provide the skills needed by a workforce shifting to remote work and increasing numbers of non-direct patient-facing laboratory roles. Drawing upon our years of experience, GeneDx aims to actively contribute to discussions around these questions. Alongside other laboratories and training programs, we hope to foster further innovation surrounding the training needs of our future GC colleagues. This educational innovation illustrates an approach to helping genetic counseling students achieve competencies related to lab-based roles.

Mixed methods evaluation of pediatric telehealth equity for patients/families who communicate in languages other than English.

Background: Emerging research demonstrates telehealth disparities for patients who communicate in languages other than English. A better understanding of pediatric telehealth use with families who communicate in languages other than English is needed to inform interventions to promote telehealth equity. Methods: We conducted a mixed methods study of telehealth care in a children's hospital health system using electronic health record data for outpatient video telehealth encounters from April 2020 to July 2021 and qualitative interviews with clinical staff and Spanish-speaking parents of telehealth patients. Results: The 16-month study period included 102,387 telehealth encounters; 5% of which were encounters in languages other than English. 83% of languages other than English encounters were with patients/families with a preferred healthcare language of Spanish. 11% of providers conducted ≥10 languages other than English telehealth encounters. This subset of providers conducted 71% of all languages other than English encounters. We conducted 25 interviews with clinical staff (n=13) and parents (n=12). Common themes identified across interviews were: (I) technology barriers affect access to and quality of telehealth; (II) clinical staff and parents are uncertain about the future role of telehealth for patients/families who communicate in languages other than English; (III) the well-known impact of language barriers on in-person healthcare access and quality for patients who communicate in languages other than English is also evident in telehealth. Conclusions: Patients who communicate in languages other than English were underrepresented among telehealth encounters and encounters were concentrated among few providers. Promoting equitable telehealth care requires investment to address technology barriers, increase the readiness of providers and clinics to provide telehealth care in languages other than English, and continued attention to reducing the healthcare impact of language barriers.

Detecting and Characterizing Particulate Organic Nitrates with an Aerodyne Long-ToF Aerosol Mass Spectrometer.

Particulate organic nitrate (pON) can be a major part of secondary organic aerosol (SOA) and is commonly quantified by indirect means from aerosol mass spectrometer (AMS) data. However, pON quantification remains challenging. Here, we set out to quantify and characterize pON in the boreal forest, through direct field observations at Station for Measuring Ecosystem Atmosphere Relationships (SMEAR) II in Hyytiälä, Finland, and targeted single-precursor laboratory studies. We utilized a long time-of-flight AMS (LToF-AMS) for aerosol chemical characterization, with a particular focus to identify C x H y O z N+ ("CHON+") fragments. We estimate that during springtime at SMEAR II, pON (including both the organic and nitrate part) accounts for ∼10% of the particle mass concentration (calculated by the NO+/NO2 + method) and originates mainly from the NO3 radical oxidation of biogenic volatile organic compounds. The majority of the background nitrate aerosol measured is organic. The CHON+ fragment analysis was largely unsuccessful at SMEAR II, mainly due to low concentrations of the few detected fragments. However, our findings may be useful at other sites as we identified 80 unique CHON+ fragments from the laboratory measurements of SOA formed from NO3 radical oxidation of three pON precursors (ß-pinene, limonene, and guaiacol). Finally, we noted a significant effect on ion identification during the LToF-AMS high-resolution data processing, resulting in too many ions being fit, depending on whether tungsten ions (W+) were used in the peak width determination. Although this phenomenon may be instrument-specific, we encourage all (LTOF-) AMS users to investigate this effect on their instrument to reduce the possibility of incorrect identifications.

Use of Predictive Analytics to Identify Unhealthy Opioid Use and Guide Intervention.

OBJECTIVE: The authors aimed to use the newly developed Opioid Risk Stratification Tool to identify individuals who may be at risk for unhealthy opioid use and to examine the impact of applying a mailing and engagement intervention to this population and their prescribers, with the goal of reducing high-risk prescribing behaviors, opioid medication use, and mortality rates. METHODS: A nonrandomized controlled study was conducted with members from two Medicaid managed care organizations. In both the intervention (N=131) and control (N=187) groups, an algorithm identified members at moderate to high risk for hazardous opioid use. Members at increased risk in the intervention group and their prescribers received a letter from the managed care organization, and members still at risk 3 months after the mailing were contacted by a care coordinator. Individuals in the control group were not contacted. Medicaid claims data were used to compare opioid use and prescribing practices between groups before and after the intervention. RESULTS: Individuals in the intervention group were less likely to have any opioid prescription postintervention compared with those in the control group (OR=0.55, p<0.001), and the intervention group had a greater reduction in the number of individuals with concurrent opioid and benzodiazepine prescriptions (OR=0.49, p=0.042). Practices such as multiple opioid prescriptions and multiple prescribers of opioids were not affected by the intervention. CONCLUSIONS: An intervention targeting individuals at risk for hazardous opioid use was associated with a reduction in some high-risk prescribing practices. Future research should determine the ideal mix of interventions to reduce as many risk factors as possible.

Activity patterns and reproductive behavior of the Critically Endangered Bermuda skink (Plestiodon longirostris).

The study of rare or cryptic species in zoos can provide insights into natural history and behavior that would be difficult to obtain in the field. Such information can then be used to refine population assessment protocols and conservation management. The Bermuda skink (Plestiodon longirostris) is an endemic Critically Endangered lizard. Chester Zoo's successful conservation breeding program is working to safeguard, increase and reinforce skink populations in the wild. A key aim of this program is to develop our understanding of the behavior of this species. In this study, using 24 h video recordings, we examined the daily activity patterns, basking behavior and food preferences of four pairs of Bermuda skinks. The skinks displayed a bimodal pattern of activity and basking, which may have evolved to avoid the strength of the midday sun in exposed habitats in Bermuda. Captive Bermuda skinks appear to prefer a fruit-based diet to orthopteran prey. We also documented their reproductive behavior and compared it against two closely related species. Although there were many similarities between the courtship and mating behaviors of the three species, there was a significantly shorter period of cloacal contact in the Bermuda skink. Oophagia was also documented for the first time in this species. This knowledge has enabled the evaluation of the current ex-situ management practices of this species, filled gaps in knowledge that would be challenging to obtain in the field, and enabled the enhancement of both animal husbandry and reproductive success for the conservation breeding program.

An innate ability: How do basal invertebrates manage their chronic exposure to microbes?

Homologs of mammalian innate immune sensing and downstream pathway proteins have been discovered in a variety of basal invertebrates, including cnidarians and sponges, as well as some single-celled protists. Although the structures of these proteins vary among the basal organisms, many of the activities found in their mammalian counterparts are conserved. This is especially true for the Toll-like receptor (TLR) and cGAS-STING pathways that lead to downstream activation of transcription factor NF-κB. In this short perspective, we describe the evidence that TLR and cGAS-STING signaling to NF-κB is also involved in immunity in basal animals, as well as in the maintenance of microbial symbionts. Different from terrestrial animals, immunity in many marine invertebrates might have a constitutively active state (to protect against continual exposure to resident or waterborne microbes), as well as a hyperactive state that can be induced by pathogens at both transcriptional and posttranscriptional levels. Research on basal immunity may be important for (1) understanding different approaches that organisms take to sensing and protecting against microbes, as well as in maintaining microbial symbionts; (2) the identification of novel antimicrobial effector genes and processes; and (3) the molecular pathways that are being altered in basal marine invertebrates in the face of the effects of a changing environment.

White Tongue Because of Uremic Stomatitis as a Sign of Advanced Kidney Disease.

We present a case of a previously healthy adolescent male who initially presented to his primary care physician with the chief complaint of a "large and white tongue," who subsequently was diagnosed with end-stage kidney disease (ESKD) and associated uremic stomatitis. This patient required admission to a PICU for acute renal replacement therapy with intermittent hemodialysis, and his hospital course was complicated by generalized tonic-clonic seizures. ESKD is difficult to diagnose in the pediatric population because these patients are often asymptomatic in the early stages given the insidiousness of underlying disorders. Renal disease should be considered in the differential diagnosis of a child with a white tongue not being the result of oral candidiasis.

Island Life: Use of Activity Budgets and Visibility to Evaluate a Multi-Species Within-Zoo Exhibit Move.

Modern zoos strive to construct habitats which both enable and encourage animals to engage in species-specific behaviour, without compromising their visibility to visitors. Here, we present the findings of a within-zoo move to a custom-built exhibit (Islands at Chester Zoo, UK) with respect to the behaviour of four mammal species; the Sumatran orangutan (Pongo abelii), crested macaque (Macaca nigra), Malayan tapir (Tapirus indicus) and the Malayan sun bear (Helarctos malayanus). We used full activity budgets along with Compositional Data Analysis (CoDA) to gain insight into how the move to a more naturalistic exhibit influenced behaviour. Engagement in abnormal behaviour remained low during the study period for all four species, suggesting no adverse responses to the change in environment. Following the move, both the non-human primate species spent more time engaged in positive social interactions with conspecifics, highlighting the importance of social support during enclosure moves. Time spent visible to the public was largely unaffected by the enclosure move for the Sumatran orangutan, whilst the movement to a new environment increased visibility for the Malayan sun bear and decreased visibility for the crested macaque and Malayan tapir. We demonstrate the value of monitoring behaviour throughout the translocation of zoo-housed species and outline the positive behavioral impacts of providing individuals with naturalistic, species-appropriate environments.

Investigating the Sources of Urban Air Pollution Using Low-Cost Air Quality Sensors at an Urban Atlanta Site.

Advances in low-cost sensors (LCS) for monitoring air quality have opened new opportunities to characterize air quality in finer spatial and temporal resolutions. In this study, we deployed LCS that measure both gas (CO, NO, NO2, and O3) and particle concentrations and co-located research-grade instruments in Atlanta, GA, to investigate the capability of LCS in resolving air pollutant sources using non-negative matrix factorization (NMF) in a moderately polluted urban area. We provide a comparison of applying the NMF technique to both normalized and non-normalized data sets. We identify four factors with different temporal trends and properties for both normalized and non-normalized data sets. Both normalized and non-normalized LCS data sets can resolve primary organic aerosol (POA) factors identified from research-grade instruments. However, applying normalization provides factors with more diverse compositions and can resolve secondary organic aerosol (SOA). Results from this study demonstrate that LCS not only can be used to provide basic mass concentration information but also can be used for in-depth source apportionment studies even in an urban setting with complex pollution mixtures and relatively low aerosol loadings.

Electrospinning of stimuli-responsive polymers for controlled drug delivery: pH- and temperature-driven release.

Stimuli-responsive polymers have attracted academic interest over the last 60 years due to their potential use in developing systems with a range of functionalities that can be activated by external artificial triggers. The diversity of responses and stimuli, which can be achieved through careful polymer selection and processing, opens up applications in nearly every sector. In particular, the use of responsive polymers for the controlled delivery of drugs and bioactive compounds has been heavily researched. This review provides an overview of the recent advancements in electrospinning of temperature- and pH-responsive polymers to create networks of nanofibres with controlled drug delivery profiles for biomedical applications.

Comparison of NF-κB from the protists Capsaspora owczarzaki and Acanthoeca spectabilis reveals extensive evolutionary diversification of this transcription factor.

We provide a functional characterization of transcription factor NF-κB in protists and provide information about the evolution and diversification of this biologically important protein. We characterized NF-κB in two protists using phylogenetic, cellular, and biochemical techniques. NF-κB of the holozoan Capsaspora owczarzaki (Co) has an N-terminal DNA-binding domain and a C-terminal Ankyrin repeat (ANK) domain, and its DNA-binding specificity is more similar to metazoan NF-κB proteins than to Rel proteins. Removal of the ANK domain allows Co-NF-κB to enter the nucleus, bind DNA, and activate transcription. However, C-terminal processing of Co-NF-κB is not induced by IκB kinases in human cells. Overexpressed Co-NF-κB localizes to the cytoplasm in Co cells. Co-NF-κB mRNA and DNA-binding levels differ across three Capsaspora life stages. RNA-sequencing and GO analyses identify possible gene targets of Co-NF-κB. Three NF-κB-like proteins from the choanoflagellate Acanthoeca spectabilis (As) contain conserved Rel Homology domain sequences, but lack C-terminal ANK repeats. All three As-NF-κB proteins constitutively enter the nucleus of cells, but differ in their DNA-binding abilities, transcriptional activation activities, and dimerization properties. These results provide a basis for understanding the evolutionary origins of this key transcription factor and could have implications for the origins of regulated immunity in higher taxa.

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing.

Cryogels are macroporous polymeric structures formed from the cryogelation of monomers/polymers in a solvent below freezing temperature. Due to their inherent interconnected macroporosity, ease of preparation, and biocompatibility, they are increasingly being investigated for use in biomedical applications such as 3D-bioprinting, drug delivery, wound healing, and as injectable therapeutics. This review highlights the fundamentals of macroporous cryogel preparation, cryogel properties that can be useful in the highlighted biomedical applications, followed by a comprehensive review of recent studies in these areas. Research evaluated includes the use of cryogels to combat various types of cancer, for implantation without surgical incision, and use as highly effective wound dressings. Furthermore, conclusions and outlooks are discussed for the use of these promising and durable macroporous cryogels.

Molecular and Biochemical Approaches to Study the Evolution of NF-κB Signaling in Basal Metazoans.

Extensive genomic and transcriptomic sequencing over the past decade has revealed NF-κB signaling pathway homologs in organisms basal to insects, for example, in members of the phyla Cnidaria (e.g., sea anemones, corals, hydra, jellyfish) and Porifera (sponges), and in several single-celled protists (e.g., Capsaspora owczarzaki, some choanoflagellates). Therefore, methods are required to study the function of NF-κB and its pathway members in early branching organisms, many of which do not have histories as model organisms. Here, we describe a combination of cellular, molecular, and biochemical techniques that have been used for studying NF-κB, and related pathway proteins, in some of these basal organisms. These methods are useful for studying the evolution of NF-κB signaling, and may be adaptable to the study of NF-κB in other non-model organisms.

Three Cases of Severe ME/CFS in Adults.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, only partially understood multi-system disease whose onset and severity vary widely. Symptoms include overwhelming fatigue, post-exertional malaise, sleep disruptions, gastrointestinal issues, headaches, orthostatic intolerance, cognitive impairment, etc. ME/CFS is a physiological disease with an onset often triggered by a viral or bacterial infection, and sometimes by toxins. Some patients have a mild case and are able to function nearly on a par with healthy individuals, while others are moderately ill and still others are severely, or even, very severely ill. The cohort of moderately to very severely ill is often housebound or bedbound, has lost employment or career, and has engaged in a long, and often futile, search for treatment and relief. Here, we present three case studies, one each of a moderately ill, a severely ill, and a very severely ill person, to demonstrate the complexity of the disease, the suffering of these patients, and what health care providers can do to help.

The uses and implications of avian vocalizations for conservation planning.

There is a growing recognition that animal behavior can affect wildlife conservation, but there have been few direct studies of animal behavior in conservation programs. However, a great deal of existing behavioral research can be applied in the context of conservation. Research on avian vocalizations provides an excellent example. The conspicuous nature of the vocal behavior of birds makes it a useful tool for monitoring populations and measuring biodiversity, but the importance of vocalizations in conservation goes beyond monitoring. Geographic song variants with population-specific signatures, or dialects, can affect territory formation and mate choice. Dialects are influenced by cultural evolution and natural selection and changes can accumulate even during the timescale of conservation interventions, such as translocations, reintroductions, and ex situ breeding. Information from existing research into avian vocalizations can be used to improve conservation planning and increase the success of interventions. Vocalizations can confer a number of benefits for conservation practitioners through monitoring, providing baseline data on populations and individuals. However, the influence of cultural variation on territory formation, mate choice, and gene flow should be taken into account because cultural differences could create obstacles for conservation programs that bring birds from multiple populations together and so reduce the success of interventions.

Implicaciones y Usos de las Vocalizaciones de Aves para la Conservación de la Planeación Resumen Hay un creciente reconocimiento de que el comportamiento animal puede afectar a la conservación de la fauna, pero ha habido pocos estudios directos del comportamiento animal en los programas de conservación. Sin embargo, una gran cantidad de la investigación existente sobre el comportamiento puede aplicarse en el contexto de la conservación. Las investigaciones sobre las vocalizaciones de aves son un excelente ejemplo. La naturaleza conspicua del comportamiento vocal de las aves hace que sea una herramienta útil para el monitoreo de las poblaciones y las medidas de la biodiversidad, pero la importancia de las vocalizaciones en la conservación va más allá del monitoreo. Las variantes geográficas de canto con firmas específicas para cada población, también conocidas como dialectos, pueden afectar a la formación del territorio y a la elección de pareja. Los dialectos están influenciados por la evolución cultural y la selección natural y los cambios pueden acumularse incluso durante la escala de tiempo de las intervenciones de conservación, como las reubicaciones, las reintroducciones y la reproducción ex situ. La información disponible a partir de las investigaciones existentes sobre las vocalizaciones de aves puede usarse para mejorar la planeación de la conservación e incrementar el éxito de las intervenciones. Las vocalizaciones pueden otorgar un número de beneficios para quienes practican la conservación a través del monitoreo, proporcionando información de la línea base de las poblaciones y los individuos. Sin embargo, la influencia de la variación cultural sobre la formación del territorio, la elección de pareja y el flujo génico deberían considerarse ya que las diferencias culturales podrían crear obstáculos para los programas de conservación que agrupan a aves de diferentes poblaciones y con ello reducen el éxito de las intervenciones.

Looking Down on NF-κB.

The diversified NF-κB transcription factor family has been extensively characterized in organisms ranging from flies to humans. However, homologs of NF-κB and many upstream signaling components have recently been characterized in basal phyla, including Cnidaria (sea anemones, corals, hydras, and jellyfish), Porifera (sponges), and single-celled protists, including Capsaspora owczarzaki and some choanoflagellates. Herein, we review what is known about basal NF-κBs and how that knowledge informs on the evolution and conservation of key sequences and domains in NF-κB, as well as the regulation of NF-κB activity. The structures and DNA-binding activities of basal NF-κB proteins resemble those of mammalian NF-κB p100 proteins, and their posttranslational activation appears to have aspects of both canonical and noncanonical pathways in mammals. Several studies suggest that the single NF-κB proteins found in some basal organisms have dual roles in development and immunity. Further research on NF-κB in invertebrates will reveal information about the evolutionary roots of this major signaling pathway, will shed light on the origins of regulated innate immunity, and may have relevance to our understanding of the responses of ecologically important organisms to changing environmental conditions and emerging pathogen-based diseases.