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Abstract Background The Gorlin–Goltz syndrome (the Nevoid basal cell carcinoma syndrome (NBCCS)) is reviewed as a rare autosomal dominant syndrome caused by gene mutations located on chromosome arm 9 q. It has a variety of presentations and is characterized by basal cell carcinomas (BCC), odontogenic keratocysts (OKCs), and ectopic calcifications of the falx cerebri or plantar pits. The diagnosis depends mainly on a number of minor and major criteria. This syndrome can be misdiagnosed, which makes its early detection important in preventing consensual complications. Case presentation In our case a 50-year-old male was reported and presented with one minor and four major criteria of the Gorlin–Goltz syndrome, the first presentation was pathologically proven facial basosquamous carcinoma post-surgical excision, subsequent contrast-enhanced maxillofacial MRI as well as CT Head, Neck revealed OKCs of the maxillary and mandible as well as calcifications of the falx and vertebral fusion with palmar pits on physical examination with definite diagnosis of Gorlin–Goltz syndrome. Conclusion Gorlin–Goltz syndrome is an unusual inherited multi-systemic syndrome, which may be misdiagnosed. It is crucial that health care specialists have the necessary knowledge of the fundamental features of NBCC syndrome and the determination of its associated disorders. All patients should undergo genetic screening as well as their first-degree relatives. Morbidity can be avoided by early treatment of BCC and OKCs to avoid deformities of surrounding dermal and osseous structures.

Digital watermarking encrypts private information with the original data to protect the ownership rights of the digital asset. This paper suggests a brand-new nested watermarking technique (two-level watermarking technique) to protect copyrights of digital images. It based on a hybrid discrete wave transformation-Hessenberg decomposition-Singular value decomposition (DWT-HD-SVD). The gray-watermark image is first split into n parts, and each portion goes through two steps of watermarking, using two host images, using hybrid DWT-HD-SVD method and one final level of encryption (based on the Lightweight algorithm, the high-speed cryptographic method). The results of the simulation reveal that the suggested system offers a high level of imperceptibility, reliability and robustness. Also it can be used for both the colored and the grayed images.

Abstract The mechanism behind the acute reduction in peripheral arterial stiffness with reactive hyperemia is presumed to be flow-mediated; however, this has not been clearly demonstrated. We hypothesized that a larger reactive hyperemia magnitude would result in a greater reduction in peripheral arterial stiffness. Fourteen healthy young adults (5 females, 25 ± 5 yrs, mean ± SD) underwent reactive hyperemia with a rapid-release cuff on the upper arm inflated to 220 mmHg for 5 min: once with the arm positioned ~ 50ο above heart level and once with the arm positioned ~ 50ο below heart level. Brachial-radial pulse wave velocity (PWV) was measured with tonometers over brachial and radial arteries before cuff inflation and at 5, 15, and 30 min after release. Brachial blood flow was monitored with doppler ultrasound. At 5 min after reactive hyperemia, both the absolute (2.31 ± 1.22 vs 1.19 ± 1.19 m/sec, p = 0.007) and relative (24% vs 15%; p = 0.043) changes in brachial to radial PWV were greater with the arm below the heart compared to above the heart. The peak brachial blood flow was higher when the arm was below the heart compared to above the heart (477 $$\pm$$ ± 145 vs 369 $$\pm$$ ± 137 ml/min; p

Abstract Background There has been increased attention to the need for, and the positive impact of, engaged or participatory science in recent years. Implementation scientists have an opportunity to leverage and contribute to engagement science (ES) through the systematic integration of engagement into implementation science (IS). The purpose of this study was to gather information from researchers and others to develop a prioritized list of research needs and opportunities at the intersection of IS and ES. Methods We conducted three Zoom-based focus groups with 20 researchers to generate a list of unmet needs, barriers, and to describe normative themes about use of ES and IS. Then a panel of nine experts in IS and/or engagement ranked the needs and barriers using a survey and met via a Zoom meeting to discuss and generate research opportunities and questions, with reference to the focus group outputs. Results Respondents and experts concurred on the importance of engagement in IS. Focus group participants reported 28 needs and barriers under the themes of 1) need for best practice guidance related to engagement processes and outcomes and 2) structural barriers to integrating ES in IS. The expert panel prioritized six structural barriers and four barriers related to generating best practice guidance, with corresponding recommendations on research opportunities. Example research opportunities related to engagement processes included: define “successful” engagement in IS contexts; adapt engagement tools and best practices from other disciplines into IS. Example research opportunities related to outcomes included: assess the impact of engagement on IS outcomes; examine engagement practices that lead to optimal engaged research. Example research opportunities related to structural barriers included: leverage research evidence to create structural changes needed to expand support for engaged IS; examine factors that influence institutional buy-in of engagement in IS. Conclusions Research needs exist that relate to engagement processes, outcomes, and structural barriers, even for scientists who value engaged research. Expert panelists recommended sequential and reinforcing research opportunities that implementation and engagement scientists can tackle together to advance both fields and health equity. Future work should assess insights from broader invested parties, particularly patients and community members.

Este artículo tiene como objetivo proporcionar una descripción general de las modalidades de diagnóstico por imágenes disponibles actualmente para el estudio de los nervios periféricos. Se enfoca en la revisión de la anatomía, por cuanto un conocimiento adecuado es fundamental para la correcta interpretación de las imágenes. Se discute el uso del ultrasonido, sus indicaciones, su uso en patologías más frecuentes, ventajas y desventajas. Se analiza el uso de la resonancia magnética (RM), incluyendo la neurografía por RM, que se refiere a una optimización de las secuencias estándar para mejorar el contraste de los nervios periféricos y estructuras anatómicas adyacentes. Se mencionan además otras técnicas en desarrollo como la elastografía, que se muestra como una prometedora técnica complementaria al ultrasonido estándar, el tensor de difusión y la tractografía, discutiendo sus posibilidades futuras en el estudio de nervios periféricos.

Abstract Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown. Infant cohorts were analysed to characterise early life nasal cathelicidin levels, revealing low expression levels in the first week of life, with increased levels at 9 months which are comparable to 2-year-olds and healthy adults. No impact of prematurity on nasal cathelicidin expression was observed, nor were there effects of sex or birth mode, however, nasal cathelicidin expression was lower in the first week-of-life in winter births. Nasal cathelicidin levels were positively associated with specific inflammatory markers and demonstrated to be associated with microbial community composition. Importantly, levels of nasal cathelicidin expression were elevated in infants with mild RSV infection, but, in contrast, were not upregulated in infants hospitalised with severe RSV infection. These data suggest important relationships between nasal cathelicidin, upper airway microbiota, inflammation, and immunity against RSV infection, with interventional potential.

Abstract It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.

Abstract Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a “spaceflight signature” of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Abstract Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.

Abstract Background Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. Methods To address this issue, we used a systems biology approach utilizing NASA’s Open Science Data Repository (OSDR) on space flown murine transcriptomic datasets focused on the skin, biochemical profiles of 50 NASA astronauts and human transcriptomic datasets generated from blood and hair samples of JAXA astronauts, as well as blood samples obtained from the NASA Twins Study, and skin and blood samples from the first civilian commercial mission, Inspiration4. Results Key biological changes related to skin health, DNA damage & repair, and mitochondrial dysregulation are identified as potential drivers for skin health risks during spaceflight. Additionally, a machine learning model is utilized to determine gene pairings associated with spaceflight response in the skin. While we identified spaceflight-induced dysregulation, such as alterations in genes associated with skin barrier function and collagen formation, our results also highlight the remarkable ability for organisms to re-adapt back to Earth via post-flight re-tuning of gene expression. Conclusion Our findings can guide future research on developing countermeasures for mitigating spaceflight-associated skin damage.

Resumo Neste dossiê, congregamos pesquisas que descrevem e analisam relações constituídas sob o efeito dos big data. A partir de espaços bastante distintos entre si - o jurídico, o burocrático, o agrícola, o biotecnológico, o econômico, o pornográfico -, voltamo-nos às agências conflitivas e criativas implicadas no que os dados fazem ver e no que são capazes de criar por meio de seu potencial de hiper-relacionalidade. Discutimos, então, a relação dos volumosos bancos de dados com aparatos diversos, como aplicativos, satélites, microscópios, documentos e algoritmos, capazes de arranjar e distribuir elementos informacionais por meio de práticas comparativas. Examinamos procedimentos de coleta e processamento de big data em diferentes setores e instituições; a pulverização das linguagens algorítmicas e estatísticas; as exigências crescentes por transparência, precisão e celeridade; a vinculação entre o tratamento de dados e as possibilidades de desenvolvimento democrático e sustentável. É dada especial atenção às transformações éticas e epistemológicas que envolvem os big data, bem como os efeitos da mobilização de conhecimentos computacionais por especialistas, incluídos aí os/as próprios/as antropólogos/as, em diferentes ambientes de produção de conhecimento.

Resumo Este artigo contribui para os debates acerca dos conceitos de acesso e de democratização do sistema de justiça por meio da atenção a circuitos técnico-burocráticos ainda pouco inspecionados pela antropologia interessada no direito: os que, depois de promulgadas as sentenças, se encarregam de sua organização e divulgação em ferramentas de busca digitais. Pelo exame de documentos institucionais do Superior Tribunal de Justiça (STJ), descrevo a jurisprudência não como o resultado direto dos julgamentos de tribunais superiores, mas como o produto de um complexo trabalho técnico-documental, realizado por analistas humanos e aplicativos computacionais, que recorre a comparações, sínteses e extensões de documentos abrigados em uma volumosa base de dados. Demonstro como a gestão desta base e a confecção de “representações digitais” das sentenças promulgadas intrincam-se ao conceito de uniformização, central às atividades do Tribunal. Argumento, enfim, que o apelo democrático do STJ, a despeito das numerosas cancelas que cerceiam suas entradas, ancora-se contemporaneamente na disponibilização cuidadosa de seus enunciados a todos os usuários que tenham acesso à internet.

Recent studies have highlighted the importance of host-associated microbial communities in inhibiting growth or colonization of pathogenic species and mitigating disease severity. Much research has been conducted on how the microbiome of individuals may impact their disease susceptibility; however, less attention has been given to the role of microbiomes in population-level disease processes. In this study, we examined the effects of the ocular microbiome on pathogen load, disease severity, and transmission success of the conjunctival bacterial pathogen Mycoplasma gallisepticum (MG) in house finches (Haemorhous mexicanus). Fifteen male house finches were exposed to MG and housed pairwise with uninfected females for 32 days. Swabs for ocular microbiome characterization via 16 S rRNA gene amplicon sequencing were collected from male and female finches before and nine days after MG inoculation. MG load and disease severity were quantified throughout the experiment for all individuals. We examined whether ocular microbiome composition prior to MG infection was associated with pathogen load, disease severity, or transmission efficacy. Although the presence of certain taxa in the ocular microbiome is associated with disease protection in this species, we did not find any evidence that ocular microbiome composition was associated with any metric used to quantify disease transmission. MG infection did alter the resident bacterial communities, which aligns with results from previous studies. However, this was only true for the indicator birds that were directly inoculated with MG. Our results suggest the resident ocular microbiome of house finches shifts in responses to direct contact with pathogens, but may be more resilient, at least at the timescales examined, when host exposure is via an infected conspecific. This suggests that outcomes of interactions between pathogens and resident microbial communities may depend on the mode or dose of pathogen exposure.

In this work, we advocate agroforestry as a sustainable agricultural method that leverages biodiversity and ecosystem services, simultaneously tackling the problems of adaptation and mitigation to climate change, and of land restoration for sustainable agriculture across scales. While the rise of industrial agriculture has been instrumental in addressing the food demands of an expanding global population, enhancing food quality, yield, productivity, and efficiency, we must now reckon with the consequences. This advancement, which prioritizes simplification, specialization, and external inputs, has escalated detrimental externalities including deforestation, biodiversity loss, soil degradation, pollution, and an increase in greenhouse gases, contributing significantly to global warming and to exacerbated environmental crises. These demand urgent attention. In response, various agricultural methodologies such as organic, biodynamic, ecological, and biological farming have emerged, attempting to propose alternatives. However, these methods have yet to significantly alter the trajectory of mainstream agriculture. For over two decades, we have devoted our efforts to developing and refining a multispecies integrated agroforestry system for the sustainable cultivation of Ilex paraguariensis, “yerba mate,” in the subtropical north-east of Argentina. With “integrated” we mean that the trees are planted within the I. paraguariensis distribution, not between alleys as in “alley cropping” or “hedgrow intercropping.” The experimental work we present here was designed and implemented to enable data comparisons across consociations of multiple species of trees, at a relevant experimental scale. We achieve soil preservation and restoration, productivity comparable to or exceeding monocultures, and a significant increase in resiliency, particularly evidenced during the extreme climate events of spring and summer 2021 and 2022. These results underscore agroforestry’s potential for climate change mitigation and adaptation.

In this paper, Benson, Blumenthal, and Klosek summarize the proceedings of the public symposium on the “Protection of Copyright User Rights from Contractual Override.” The American Library Association (ALA) and the Association of Research Libraries (ARL)—together, the Library Copyright Alliance (LCA)—sponsored the symposium in partnership with the American University Washington College of Law Program on Information Justice and Intellectual Property (PIJIP). The paper includes summaries of each panel, questions that were discussed, and takeaways for the library community to consider. Keywords: copyright, contracts, public policy, limitations and exceptions

The Mark and Gail Appel Program in Holocaust and Antiracism Education: “Learning from the Past, Teaching for the Future” (TFTF) is a tri-national program that brings students from Canada, Germany, and Poland to sites of Holocaust memory to focus on the history, experience, representation, and memorialization of the Holocaust and its implications for other instances of atrocity, racism, and genocide. This forum gathers five voices from the 2013-2014 cohort of TFTF in order to reflect, a decade after the program, on the program’s challenges, opportunities, and lasting impacts. The forum documents the various ways TFTF has influenced the lives and career trajectories of each of the forum participants. The forum is bookended by reflections from its editors—a program organizer and a program participant—on the potentials of experiential learning, the promise of an international network of educators, and the processing that a program like TFTF continues to demand.

Given that ecosystems are composed of sounds created by geophysical events (e.g., wind, rain), animal behaviors (e.g., dawn songbird chorus), and human activities (e.g., tourism) that depend on seasonal climate conditions, the phenological patterns of a soundscape could be coupled with long-term weather station data as a complimentary ecological indicator of climate change. We tested whether the seasonality of the soundscape coincided with common weather variables used to monitor climate. We recorded ambient sounds hourly for five minutes (01 January–30 June) over three years (2019–2021) near a weather station in a subarctic ecosystem in south-central Alaska. We quantified sonic information using the Acoustic Complexity Index (ACItf), coupled with weather data, and used machine learning (TreeNet) to identify sonic-climate relationships. We grouped ACItf according to time periods of prominent seasonal events (e.g., days with temperatures >0°C, no snow cover, green up, dawn biophony, and road-based tourism) and identified distinct sonic phenophases (sonophases) for groups with non-overlapping 95% confidence intervals. In general, sonic activity increased dramatically as winter transitioned to spring and summer. We identified two winter sonophases, a spring sonophase, and a summer sonophase, each coinciding with hours of daylight, temperature, precipitation, snow cover, and the prevalence of animal and human activities. We discuss how sonophases and weather data combined serve as a multi-dimensional, systems-based approach to understanding the ecological effects of climate change in subarctic environments.

Abstract Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA‐sequencing was performed on flow‐sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA‐sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF‐β1 and TNF‐α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro‐fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up‐regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro‐fibrotic effect of TGF‐β1. RNA‐sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Using hydrochemical and isotopic compositions of springs and wells, we trace carbon from critical zone carbon dioxide (CO2) into groundwater of the semi-arid Reynolds Creek Experimental Watershed - Critical Zone Observatory, southwestern Idaho, USA. Dissolved inorganic carbon (DIC) concentrations, pH and stable isotope tracers of carbon for DIC (δ13CDIC), are used to show that most groundwater evolves under open system conditions, moving carbon into the groundwater and acting as a carbon sink. However, one sample (−10.94‰ δ13CDIC, 6,350 14C years before present (yrs. BP)) may have evolved under closed system conditions with a higher partial pressure of critical zone CO2 than present-day soils. By characterizing the carbon cycle, we show that (1) carbon evolution is primarily under open-system conditions, (2) shallow groundwater samples are generally less mixed and more recent (10 to 70 3H yrs. BP) than deeper groundwater samples (1,469 to 6,350 14C yrs. BP), and (3) the older portion of the groundwater may be even older than the calculated 14C ages, as indicated by the mixing of age tracers in intermediate wells. Our global conception of the deep critical zone should include carbon cycling of critical zone CO2 in old groundwater. Characterizing the deep critical zone in a semi-arid weathered silicate watershed improves our global understanding of carbon, nutrient and water cycling.

Abstract Cocaine disrupts dopamine (DA) and kappa opioid receptor (KOR) system activity, with long-term exposure reducing inhibiton of DA uptake by cocaine and increasing KOR system function. Single treatment therapies have not been successful for cocaine use disorder; therefore, this study focuses on a combination therapy targeting the dopamine transporter (DAT) and KOR. Sprague Dawley rats self-administered 5 days of cocaine (1.5 mg/kg/inf, max 40 inf/day, FR1), followed by 14 days on a progressive ratio (PR) schedule (0.19 mg/kg/infusion). Behavioral effects of individual and combined administration of phenmetrazine and nBNI were then examined using PR. Additionally, ex vivo fast scan cyclic voltammetry was then used to assess alterations in DA and KOR system activity in the nucleus accumbens before and after treatments. Chronic administration of phenmetrazine as well as the combination of phenmetrazine and nBNI—but not nBNI alone—significantly reduced PR breakpoints. In addition, the combination of phenmetrazine and nBNI partially reversed cocaine-induced neurodysregulations of the KOR and DA systems, indicating therapeutic benefits of targeting the DA and KOR systems in tandem. These data highlight the potential benefits of the DAT and KOR as dual-cellular targets to reduce motivation to administer cocaine and reverse cocaine-induced alterations of the DA system.

This work investigates and analyzes collaborative beamforming for a Swarm-enabled distributed sensing project. It investigates the use of a three-dimensional, randomly populated, and uniformly-distributed array in three configurations: spherical, cylindrical, and cubical. These topologies uniquely act like a practical bound to contain the elements in swarm-type applications. In addition, these topologies provide mathematical simplicity toward understanding the fundamental research problem of both surface and underwater swarm-based UUV sensor networks, and their constraints to implementing a physical system in a volumetric setting. Therefore, statistical, ensemble, mean-valued average beampatterns scanned at the meridian elevation plane are analyzed in closed form using a large population of one million elements densely populated amongst geometrical bounds. This large density profile applies the law of large numbers in which numerical beampatterns converge to their expected (mean) patterns. Faithful agreement of the solution is shown to validate the distributed array pattern behavior. Finally, additional simulations are provided in this work using a cylindrical manifold that comprises ten, fifty, and one hundred isotropic radiators to determine the feasibility of a small element population.

Background: One of the most prevalent chronic illnesses in the nation and the world is diabetes. It remains as one of the leading cause of death so it's important to create cutting-edge, potentially cost-effective co-treatment techniques derived from plants that don't have any negative impacts. Previous research has shown that watercress (Nasturtium officinale) possesses anti-inflammatory, antioxidant, and anti-diabetic properties. Objectives: to investigate the effects of watercress aqueous extract on gene expression of glucose transporter 4 (GLUT4) and 5’ AMP-activated protein kinase (AMPK) in streptozotocin induced diabetic rats. Materials and methods: Sixty healthy male albino rats were used in this study. Animals were split into four equal groups, each of 15 rats. Group 1: (Negative Control), Group 2: (Diabetes Positive Control injected with (45mg/kg body weight) Streptozotocin intraperitoneally), Group 3 (diabetic rats received 100 mg of watercress aqueous extract /Kg body weight for 8 weeks, daily) and Group 4 (diabetic rats received 200 mg of watercress aqueous extract /Kg body weight for 8 weeks, daily). Blood was collected after scarification on weeks 2, 4, 6, and 8 of the experiment for serum separation and pancreatic tissues were collected on weeks 4 and 8 of the experiment. Fasting blood glucose as measured by glucometer, insulin hormone was measured by ELISA kit.Triglyceride, LDL, HDL, creatinine, urea, AST and ALT were measured by spectrophotometer. SYBR Green qPCR Master Mix was used for measurement of GLUT4, AMPK and Beta-actin. Results: The treated group exhibited a significant and progressive decrease in fasting blood glucose, triglycerides, total cholesterol, LDL, HDL, creatinine, urea, ALT, and AST and a significant and progressive increase in insulin hormone at all experiment times compared to the controls. The 4th group exhibited a significant and progressive up regulation gene expression of GLUT4 and AMPK genes at 4 and 8 weeks compared to the controls considering watercress as an alternative treatment for diabetes. Conclusion. Watercress aqueous extract had positive effects on lowering and maintaining normal glucose levels.

Abstract Background In September 2014, there was sudden upsurge in the number of Eurasian red squirrels (Sciurus vulgaris) found dead in the Netherlands. High infection levels with the parasite Toxoplasma gondii were demonstrated, but it was unclear what had caused this increase in cases of fatal toxoplasmosis. In the present study, we aimed to gain more knowledge on the pathology and prevalence of T. gondii infections in Eurasian red squirrels in the Netherlands, on the T. gondii genotypes present, and on the determinants of the spatiotemporal variability in these T. gondii infections. The presence of the closely related parasite Hammondia hammondi was also determined. Methods Eurasian red squirrels that were found dead in the wild or that had died in wildlife rescue centres in the Netherlands over a period of seven years (2014–2020) were examined. Quantitative real-time polymerase chain reaction was conducted to analyse tissue samples for the presence of T. gondii and H. hammondi DNA. Toxoplasma gondii-positive samples were subjected to microsatellite typing and cluster analysis. A mixed logistic regression was used to identify climatic and other environmental predictors of T. gondii infection in the squirrels. Results A total of 178 squirrels were examined (49/178 T. gondii positive, 5/178 H. hammondi positive). Inflammation of multiple organs was the cause of death in 29 squirrels, of which 24 were also T. gondii polymerase chain reaction positive. Toxoplasma gondii infection was positively associated with pneumonia and hepatitis. Microsatellite typing revealed only T. gondii type II alleles. Toxoplasma gondii infection rates showed a positive correlation with the number of days of heavy rainfall in the previous 12 months. Conversely, they showed a negative association with the number of hot days within the 2-week period preceding the sampling date, as well as with the percentage of deciduous forest cover at the sampling site. Conclusions Toxoplasma gondii infection in the squirrels appeared to pose a significant risk of acute mortality. The T. gondii genotype detected in this study is commonly found across Europe. The reasons for the unusually high infection rates and severe symptoms of these squirrels from the Netherlands remain unclear. The prevalence of T. gondii in the deceased squirrels was linked to specific environmental factors. However, whether the increase in the number of dead squirrels indicated a higher environmental contamination with T. gondii oocysts has yet to be established. Graphical Abstract

Abstract Background Given significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy. Methods The two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015—August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months. Results At 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18–0.87); higher overall health (OR = 3.14, 95%CI 1.64–6.01); greater use of the patient portal’s health/wellness resources (OR = 2.50, 95%CI 1.42–4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29–5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61–4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29–3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27–2.98). Conclusion This trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system. Trial Registration The study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. However, the potential contribution of the primary fibrinolytic protease plasminogen to PDAC disease progression has remained largely undefined. Mice bearing C57Bl/6‐derived KPC (KRasG12D, TRP53R172H) tumors displayed evidence of plasmin activity in the form of high plasmin–antiplasmin complexes and high plasmin generation potential relative to mice without tumors. Notably, plasminogen‐deficient mice (Plg‐) had significantly diminished KPC tumor growth in subcutaneous and orthotopic implantation models. Moreover, the metastatic potential of KPC cells was significantly diminished in Plg‐ mice, which was linked to reduced early adhesion and/or survival of KPC tumor cells. The reduction in primary orthotopic KPC tumor growth in Plg‐ mice was associated with increased apoptosis, reduced accumulation of pro‐tumor immune cells, and increased local proinflammatory cytokine production. Elimination of fibrin(ogen), the primary proteolytic target of plasmin, did not alter KPC primary tumor growth and resulted in only a modest reduction in metastatic potential. In contrast, deficiencies in the plasminogen receptors Plg‐RKT or S100A10 in tumor cells significantly reduced tumor growth. Plg‐RKT reduction in tumor cells, but not reduced S100A10, suppressed metastatic potential in a manner that mimicked plasminogen deficiency. Finally, tumor growth was also reduced in NSG mice subcutaneously or orthotopically implanted with patient‐derived PDAC tumor cells in which circulating plasminogen was pharmacologically reduced. Collectively, these studies suggest that plasminogen promotes PDAC tumor growth and metastatic potential, in part through engaging plasminogen receptors on tumor cells.

A good diet during pregnancy is associated with improvements to maternal and fetal health. Nevertheless, excessive weight gain during pregnancy has been reported in several studies. The aim of this review is to determine the dietary habits of pregnant women (measured according to their degree of adherence to the Mediterranean diet, a reference in dietary quality), their knowledge of food and nutrition, and their perceptions of the nutritional education received during their pregnancy, in order to detect intervention needs within that group. The bibliographic search was conducted on three databases (Medline, PubMed central, and Web of Science), using the keywords “pregnancy”, “Mediterranean diet”, “nutrition knowledge”, “nutritional education”, and some synonyms. The final selection included 68 original articles. The available evidence indicated that, although pregnant women were aware of the importance of nutrition during pregnancy, their habits showed some room for improvement in terms of diet and physical exercise. Lack of adequate advice was the main barrier to the practice of healthy habits that pregnant women encountered; they considered that the information they received during pregnancy follow-up visits was inadequate. However, the success of interventions within different countries is a source of hope for well-structured nutrition education throughout pregnancy. The lack of nutrition-related knowledge among pregnant women could be originally related to poorly planned nutrition education from healthcare providers. Research focused on the consultations with these healthcare providers could be of help when proposing strategies to improve the content, the depth, and the duration of nutrition education sessions. It should, in any case, be noted that the available evidence in this field is limited to certain geographical origins. Therefore, research that uncovers evidence in different countries will be useful for learning about the factors that condition the habits of pregnant women and, in that way, guide strategies for the improvement of the health of expectant mothers during that stage in their lives.

Wound healing is a complex and coordinated process involving interactions between cells and various messenger systems. This study conducted in vivo tests to determine the healing effect of propolis (PR)-based cream derived from the Amazon stingless bee, Scaptotrigona aff. postica, reared in açaí (Euterpe oleracea) monoculture, on induced wounds in rats. Data were obtained by monitoring injuries on 14 Wistar rats, divided into three groups (G1, G2 and G3), each receiving specific treatments: propolis-based cream (PR), collagenase (PC) and neutral cream (NC). Over the seven days of treatment, the lesions were measured using photographic records and ImageJ software to evaluate the healing effectiveness of the test cream. ImageJ software version 1.53g was used to compare the wound diameters for each treatment. After seven days, histopathological analyses of the induced lesions were performed. It was observed that collagenase (PC) and the test cream (PR) did not differ significantly in terms of wound diameter reduction. However, the propolis-based cream directly influenced the lesion maturation process and exhibited a milder inflammatory response compared to the positive control (PC). This effect is possibly associated with antimicrobial and anti-inflammatory compounds identified by GC/MS analysis in the propolis. Notably, this is the first report describing propolis of Scaptotrigona aff. postica obtained from açaí monocultures with strong healing potential, highlighting the identification of a high concentration of phenolic compounds that aid directly in wound repair.

ABSTRACT Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria Helicobacter pylori (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen Helicobacter felis (HF). Here, we identified the differences in gastric inflammation, atrophy, and metaplasia associated with HP and HF infection in mice. PMSS1 HP strain or the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages revealing that both bacteria exhibit similar immunostimulatory effects in vitro. Next, C57BL/6J mice were infected with HP or HF and were assessed 2 months post-infection. HP-infected mice caused modest inflammation within both the gastric corpus and antrum, and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced the expression of pyloric metaplasia (PM) markers. HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for studies on the effects of gastric inflammation on tumorigenesis. IMPORTANCEMouse infection models with Helicobacter species are widely used to study Helicobacter pathogenesis and gastric cancer initiation. However, Helicobacter pylori is not a natural mouse pathogen, and mouse-adapted H. pylori strains are poorly immunogenic. In contrast, Helicobacter felis is a natural mouse pathogen that induces robust gastric inflammation and is often used in mice to investigate gastric cancer initiation. Although both bacterial strains are widely used, their disease pathogenesis in mice differs dramatically. However, few studies have directly compared the pathogenesis of these bacterial species in mice, and the contrasting features of these two models are not clearly defined. This study directly compares the gastric inflammation, atrophy, and metaplasia development triggered by the widely used PMSS1 H. pylori and CS1 H. felis strains in mice. It serves as a useful resource for researchers to select the experimental model best suited for their studies.

Not available.

A case report detailing, for the first time, a case of laboratory-confirmed zoster in an astronaut on board the International Space Station is presented. The findings of reduced T-cell function, cytokine imbalance, and increased stress hormones which preceded the event are detailed. Relevance for deep space countermeasures is discussed.

BackgroundHydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual. ObjectiveThe goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study in response to a global emergency. MethodsRecruitment was anticipated to last 2 months for providers and 6 months for patients. The recruitment strategies used with patients and providers, new recruitment strategies, and recruitment rates were captured and compared. To document recruitment adaptations and their reasons, study staff responsible for recruitment completed an open-ended 9-item questionnaire eliciting challenges to recruitment and strategies used. Themes were extrapolated using thematic content analysis. ResultsTotal enrollment across the 7 sites included 89 providers and 293 patients. The study acceptance rate was 85.5% (382/447) for both patients and providers. The reasons patients declined participation were most frequently a lack of time and interest in research, while providers mostly declined because of self-perceived high levels of SCD expertise, believing they did not need the intervention. Initially, recruitment involved an in-person invitation to participate during clinic visits (patients), staff meetings (providers), or within the office (providers). We identified several important recruitment challenges, including (1) lack of interest in research, (2) lack of human resources, (3) unavailable physical space for recruitment activities, and (4) lack of documentation to verify eligibility. Adaptive strategies were crucial to alleviate enrollment disruptions due to the COVID-19 pandemic. These included remote approaching and consenting (eg, telehealth, email, and telephone) for patients and providers. Additionally, for patients, recruitment was enriched by simplification of enrollment procedures (eg, directly approaching patients without a referral from the provider) and a multitouch method (ie, warm introductions with flyers, texts, and patient portal messages). We found that patient recruitment rates were similar between in-person and adapted (virtual with multitouch) approaches (167/200, 83.5% and 126/143, 88.1%, respectively; P=.23). However, for providers, recruitment was significantly higher for in-person vs remote recruitment (48/50, 96% and 41/54, 76%, respectively, P

The biodiversity of Brazil provides an excellent climate and favorable pollination conditions for Apis mellifera L., especially in the Eastern Amazon region, which boasts vast floral wealth, including an abundance of açaí (Euterpe oleracea) flowers and fruits. In the present study, seven types of honey were evaluated: three containing floral nectar from açaí (Açaí honey) collected in the Eastern Amazon region (Açaí honey from Breu Branco (AH1 and AH2) and Açaí honey from Santa Maria (AH3), both from the state of Pará, Brazil) and four honeys from different regions of Brazil (Aroeira honey from Minas Gerais, Cipó-Uva honey from Distrito Federal, Mangue honey from Pará, and Timbó honey from Rio Grande do Sul). The characteristics of these honeys were evaluated by examining their physicochemical properties, melissopalynological aspects, color, antioxidant potential, and their constituent compounds, which were confirmed through GC-MS analysis. Açaí floral nectar honeys presented physicochemical results similar to those of other honeys, aligning with Brazilian legislation norms, but differed in their high values of free acidity, apparent sugars, and lower reducing sugars, which are directly related to their botanical origin. These differences correlate with unique flavor and distinct aroma characteristics. Melissopalynological analysis confirmed the botanical origin of the honeys containing açaí floral nectar, which had a color range from amber to dark amber. The three açaí honeys demonstrated high antioxidant capacity and superior flavonoid and polyphenol content compared to other honeys, particularly the açaí honey from Breu Branco (AH1), which had four times the content to combat free radicals compared to the honey with the highest potential (Aroeira honey). GC-MS analysis confirmed the presence of antioxidant properties as well as potential anti-inflammatory, antibacterial, antimicrobial, and antitumor capabilities in açaí honeys, which have not yet been fully studied.

Children and adolescents with autism spectrum disorder (ASD) are at a greater risk of seeking emergency department (ED) services during behavioral crises, such as acute aggression, suicidal or homicidal ideation, self-injury, or other types of challenging behavior (e.g., pica, dangerous behaviors). Research demonstrates children and adolescents with ASD often return to the ED due to challenging behavior, suggesting that gaps in care exist (e.g., follow-up appointments, referrals). However, the current knowledge basis is largely based on data from other countries. Given the unique landscape of healthcare in the United States, it is prudent to elucidate characteristics of children and adolescents with ASD who are seeking emergency care due to challenging behavior, as well as systems-level factors that both contribute to our understanding of challenging behavior and ASD in ED settings. In this study, we focus on frequency and characteristics of children and adolescents with ASD presenting to the ED with challenging behavior over the course of a 6-year period in the Midwest region of the United States. Clinical implications for ED staff are discussed.

Assessing physical activity is important in the treatment of chronic conditions, including chronic low back pain (cLBP). ActiGraph™, a widely used physical activity monitor, collects raw acceleration data, and processes these data through proprietary algorithms to produce physical activity measures. The purpose of this study was to replicate ActiGraph™ algorithms in MATLAB and test the validity of this method with both healthy controls and participants with cLBP. MATLAB code was developed to replicate ActiGraph™’s activity counts and step counts algorithms, to sum the activity counts into counts per minute (CPM), and categorize each minute into activity intensity cut points. A free-living validation was performed where 24 individuals, 12 cLBP and 12 healthy, wore an ActiGraph™ GT9X on their non-dominant hip for up to seven days. The raw acceleration data were processed in both ActiLife™ (v6), ActiGraph™’s data analysis software platform, and through MATLAB (2022a). Percent errors between methods for all 24 participants, as well as separated by cLBP and healthy, were all less than 2%. ActiGraph™ algorithms were replicated and validated for both populations, based on minimal error differences between ActiLife™ and MATLAB, allowing researchers to analyze data from any accelerometer in a manner comparable to ActiLife™.

Abstract Background Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. Indeed, KSHV infection of primary human endothelial cell cultures, even at high levels, is rarely associated with long-term culture, transformation, or growth deregulation, yet infection in vivo is sustained for life. Investigations of immune mediators that distinguish KSHV infection, KSHV/HIV co-infection, and symptomatic KS disease have yet to reveal consistent correlates of protection against or progression to KS. In addition to viral infection, it is plausible that pathogenesis also requires an immunological and metabolic environment permissive to the abnormal endothelial cell growth evident in KS tumors. In this study, we explored whether plasma metabolomes could differentiate asymptomatic KSHV-infected individuals with or without HIV co-infection and symptomatic KS from each other. Methods To investigate how metabolic changes may correlate with co-infections and tumorigenesis, plasma samples derived from KSHV seropositive sub-Saharan African subjects in three groups, (A) asymptomatic (lacking neoplastic disease) with KSHV infection only, (B) asymptomatic co-infected with KSHV and HIV, and (C) symptomatic with clinically diagnosed KS, were subjected to analysis of lipid and polar metabolite profiles Results Polar and nonpolar plasma metabolic differentials were evident in both comparisons. Integration of the metabolic findings with our previously reported KS transcriptomics data suggests dysregulation of amino acid/urea cycle and purine metabolic pathways, in concert with viral infection in KS disease progression. Conclusions This study is, to our knowledge, the first to report human plasma metabolic differentials between in vivo KSHV infection and co-infection with HIV, as well as differentials between co-infection and epidemic KS.

Abstract The vascular smooth muscle (VSM) of resistance blood vessels is a target of intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In the brain, the myogenic reactivity of cerebral arteries is critical to homeostatic blood flow regulation. Here we provide the first evidence to link the death‐associated protein kinase 3 (DAPK3) to the myogenic response of rat and human cerebral arteries. DAPK3 is a Ser/Thr kinase involved in Ca2+‐sensitization mechanisms of smooth muscle contraction. Ex vivo administration of a specific DAPK3 inhibitor (i.e., HS38) could attenuate vessel constrictions invoked by serotonin as well as intraluminal pressure elevation. The HS38‐dependent dilatation was not associated with any change in myosin light chain (LC20) phosphorylation. The results suggest that DAPK3 does not regulate Ca2+ sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. A slow return of myogenic tone was observed during the sustained ex vivo exposure of cerebral arteries to HS38. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signalling compensation in response to attenuation of DAPK3 activity. Additional experiments with VSM cells revealed HS38‐ and siDAPK‐dependent effects on the actin cytoskeleton and focal adhesion kinase phosphorylation status. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38‐dependent attenuation of myogenic reactivity found for human pial vessels.

Protein-level immunodominance patterns against Kaposi sarcoma-associated herpesvirus (KSHV), the aetiologic agent of Kaposi sarcoma (KS), have been revealed from serological probing of whole protein arrays, however, the epitopes that underlie these patterns have not been defined. We recently demonstrated the utility of phage display in high-resolution linear epitope mapping of the KSHV latency-associated nuclear antigen (LANA/ORF73). Here, a VirScan phage immunoprecipitation and sequencing approach, employing a library of 1,988 KSHV proteome-derived peptides, was used to quantify the breadth and magnitude of responses of 59 sub-Saharan African KS patients and 22 KSHV-infected asymptomatic individuals (ASY), and ultimately to support an application of machine-learning-based predictive modeling using the peptide-level responses. Comparing anti-KSHV antibody repertoire revealed that magnitude, not breadth, increased in KS. The most targeted epitopes in both KS and ASY were in the immunodominant proteins, notably, K8.129-56 and ORF65140-168, in addition to LANA. Finally, using unbiased machine-learning-based predictive models, reactivity to a subset of 25 discriminative peptides was demonstrated to successfully classify KS patients from asymptomatic individuals. Our study provides the highest resolution mapping of antigenicity across the entire KSHV proteome to date, which is vital to discern mechanisms of viral pathogenesis, to define prognostic biomarkers, and to design effective vaccine and therapeutic strategies. Future studies will investigate the diagnostic, prognostic, and therapeutic potential of the 25 discriminative peptides.

The tick Ixodes ricinus parasitizes a wide range of vertebrates. These hosts vary in the relative contribution to the feeding of the different tick life stages, and their interplay is pivotal in the transmission dynamics of tick-borne pathogens. We aimed to know if there is a phylogenetic signal in the feeding and propagation hosts of I. ricinus, independently of other traits, as well as in the amplification of Borrelia burgdorferi (s.l.) in feeding larvae. We used a compilation of 1127 published field surveys in Europe, providing data for 96,586 hosts, resulting in 265,124 larvae, 72,080 nymphs and 37,726 adults. The load of immature ticks on hosts showed a significant phylogenetic signal towards the genera Psammodromus, Podarcis, and Lacerta (nymphs only). We hypothesize that such signal is the background hallmark of the primitive hosts associations of I. ricinus, probably in the glaciation refugia. A secondary phylogenetic signal for tick immatures appeared for some genera of Rodentia and Eulipotyphla. Results suggest the notion that the tick gained these hosts after spread from glaciation refugia. Analyses support a phylogenetic signal in the tick adults, firmly linked to Cetartiodactyla, but not to Carnivora or Aves. This study provides the first demonstration of host preferences in the generalist tick I. ricinus. We further demonstrate that combinations of vertebrates contribute in different proportions supporting the tick life-cycle in biogeographical regions of the Western Palaearctic as each region has unique combinations of dominant hosts. Analysis of the amplification of B. burgdorferi (s.l.) demonstrated that each genospecies is better amplified by competent reservoirs with which a strong phylogenetic signal exists. These vertebrates are the same along the spatial range: environmental traits do not change the reservoirs along the large territory studied. The transmission of B. burgdorferi (s.l.) is amplified by a few species of vertebrates, that share biogeographical regions with the tick vector in variable proportions.

In this paper, we described a new species of Grigiotermes, G. piassava sp. n., from the Brazilian Atlantic Forest. The imago and worker caste are described, including the gut morphology. The inclusion of the new species in Grigiotermes was based on morphological and DNA data. Apparently, the distribution of the species is limited to the northern region of the Atlantic Forest, located above the São Francisco River, which is considered one of the most threatened sectors of the biome.

The management of respiratory viruses prior to hematopoietic cell transplant (HCT) can be controversial and requires special consideration of host factors, transplant parameters, and the specific respiratory virus (RV). In the setting of adenovirus (ADV), human metapneumovirus (HMPV), influenza, parainfluenza virus (PIV), and respiratory syncytial virus (RSV) detection prior to hematopoietic cell transplant (HCT), clinical practice guidelines recommend transplant delay when possible; however, there is much more ambiguity when other respiratory viruses, such as seasonal coronaviruses (CoVs), human rhinovirus (HRV), and SARS-CoV-2, are detected. Our aims for this review include detailing clinical practical guidelines and reviewing current literature on pre-transplant respiratory viral infections (RVIs), including antiviral therapies and prevention strategies, when available. We will center our discussion on three representative clinical scenarios, with the goal of providing practical guidance to clinicians.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, associated with significant burdens to patients and the healthcare system. The atrioventricular (AV) node plays a vital role in regulating heart rate during AF by filtering electrical impulses from the atria. However, it is often insufficient in regards to maintaining a healthy heart rate, thus the AV node properties are modified using rate-control drugs. Moreover, treatment selection during permanent AF is currently done empirically. Quantifying individual differences in diurnal and short-term variability of AV-nodal function could aid in personalized treatment selection.Methods: This study presents a novel methodology for estimating the refractory period (RP) and conduction delay (CD) trends, and their uncertainty in the two pathways of the AV node during 24 h using non-invasive data. This was achieved by utilizing a network model together with a problem-specific genetic algorithm and an approximate Bayesian computation algorithm. Diurnal variability in the estimated RP and CD was quantified by the difference between the daytime and nighttime estimates, and short-term variability was quantified by the Kolmogorov-Smirnov distance between adjacent 10-min segments in the 24-h trends. Additionally, the predictive value of the derived parameter trends regarding drug outcome was investigated using several machine learning tools.Results: Holter electrocardiograms from 51 patients with permanent AF during baseline were analyzed, and the predictive power of variations in RP and CD on the resulting heart rate reduction after treatment with four rate control drugs was investigated. Diurnal variability yielded no correlation to treatment outcome, and no prediction of drug outcome was possible using the machine learning tools. However, a correlation between the short-term variability for the RP and CD in the fast pathway and resulting heart rate reduction during treatment with metoprolol (ρ = 0.48, p < 0.005 in RP, ρ = 0.35, p < 0.05 in CD) were found.Discussion: The proposed methodology enables non-invasive estimation of the AV node properties during 24 h, which—indicated by the correlation between the short-term variability and heart rate reduction—may have the potential to assist in treatment selection.

ABSTRACT Importance Despite the high burden of respiratory infections among children, the production of exhaled particles during common activities and the efficacy of face masks in children have not been sufficiently studied. Objective To determine the effect of type of activity and mask usage on exhaled particle production in children. Methods Healthy children were asked to perform activities that ranged in intensity (breathing quietly, speaking, singing, coughing, and sneezing) while wearing no mask, a cloth mask, or a surgical mask. The concentration and size of exhaled particles were assessed during each activity. Results Twenty‐three children were enrolled in the study. Average exhaled particle concentration increased by intensity of activity, with the lowest particle concentration during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]) and highest particle concentration during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High‐intensity activities were associated with an increase primarily in the respirable size (≤ 5 µm) particle fraction. Surgical and cloth masks were associated with lower average particle concentration compared to no mask (P = 0.026 for sneezing). Surgical masks outperformed cloth masks across all activities, especially within the respirable size fraction. In a multivariable linear regression model, we observed significant effect modification of activity by age and by mask type. Interpretation Similar to adults, children produce exhaled particles that vary in size and concentration across a range of activities. Production of respirable size fraction particles (≤ 5 µm), the dominant mode of transmission of many respiratory viruses, increases significantly with coughing and sneezing and is most effectively reduced by wearing surgical face masks.

Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of gene therapy approaches. Generally, inducible ON systems require a chimeric transcription factor (transactivator) that becomes activated by an inductor, which is not optimal for clinical translation due to their toxicity. We generated previously the first all-in-one, transactivator-free, doxycycline (Dox)-responsive (Lent-On-Plus or LOP) lentiviral vectors (LVs) able to control transgene expression in human stem cells. Here, we have generated new versions of the LOP LVs and have analyzed their applicability for the generation of inducible advanced therapy medicinal products (ATMPs) with special focus on primary human T cells. We have shown that, contrary to all other cell types analyzed, an Is2 insulator must be inserted into the 3′ long terminal repeat of the LOP LVs in order to control transgene expression in human primary T cells. Importantly, inducible primary T cells generated by the LOPIs2 LVs are responsive to ultralow doses of Dox and have no changes in phenotype or function compared with untransduced T cells. We validated the LOPIs2 system by generating inducible CAR-T cells that selectively kill CD19+ cells in the presence of Dox. In summary, we describe here the first transactivator-free, all-one-one system capable of generating Dox-inducible ATMPs.

Prior studies examining the effects of cocaine on the dynorphin/kappa opioid receptor (Dyn/KOR) system primarily focus on non-contingent cocaine exposure, but the effects of self-administration, which more closely reflects human drug-taking behaviors, are not well studied. In this study we characterized the effects of escalated intravenous cocaine self-administration on the functional state of the Dyn/KOR system and its interaction with mesolimbic dopamine signaling. Rats self-administered cocaine in an extended access, limited intake cocaine procedure, in which animals obtained 40 infusions per day (1.5 mg/kg/inf) for 5 consecutive days to ensure comparable consumption levels. Following single day tests of cue reactivity and progressive ratio responding, quantitative real-time polymerase chain reaction was used to measure levels of Oprk and Pdyn transcripts in the ventral tegmental area and nucleus accumbens. Additionally, after self-administration, ex vivo fast-scan cyclic voltammetry in the NAc was used to examine the ability of the KOR agonist U50,488 to inhibit dopamine release. We found that KOR-induced inhibition of dopamine release was enhanced in animals that self-administered cocaine compared to controls, suggesting upregulated Dyn/KOR activity after cocaine self-administration. Furthermore, expression levels of Pdyn in the nucleus accumbens and ventral tegmental area, and Oprk in the nucleus accumbens, were elevated in cocaine animals compared to controls. Additionally, Pdyn expression in the nucleus accumbens was negatively correlated with progressive ratio breakpoints, a measure of motivation to self-administer cocaine. Overall, these data suggest that cocaine self-administration elevates KOR/Dyn system activity in the mesolimbic dopamine pathway.

Abstract The acute reduction in peripheral arterial stiffness during reactive hyperemia is assumed to be flow‐mediated; however, the mechanism remains unproven. We hypothesized that restricting the blood flow increase during reactive hyperemia would abolish the reduction in peripheral arterial stiffness. Fourteen healthy young adults (5 females, 25 ± 5 years, mean ± SD) underwent reactive hyperemia with a rapid‐release cuff on the upper arm inflated to 220 mmHg for 5 min: once with unrestricted blood flow and once with restricted blood flow by manually applying pressure to the brachial artery. Brachial–radial pulse wave velocity (PWV) was measured with tonometers over brachial and radial arteries before cuff inflation and at 5, 15, and 30 min after release. Brachial blood flow was monitored with Doppler ultrasound. Baseline brachial–radial PWV was similar between conditions (10.3 ± 1.8 vs. 10.7 ± 1.7 m/s). With unrestricted flow, PWV decreased 5 min post‐reactive hyperemia (8.6 ± 1.1 m/s; p 0.05) post‐reactive hyperemia. Reactive hyperemia acutely reduced peripheral arterial stiffness, but not when brachial artery blood flow increase was restricted. This suggests that the reduction in peripheral arterial stiffness during reactive hyperemia depends on increased blood flow.

With roughly 3.9 million acres of wetlands, 2.3% of its total land area, Texas has the fifth largest wetland acreage in the United States. As of 1990, there was an estimated 52% reduction in the state's original wetland acreage, but there has been no recent assessment of statewide wetland loss or gain since then. Wetlands provide critical ecosystem services, including wildlife habitat, flood storage and control, aquifer recharge, water quality improvement, and pollutant breakdown and storage of greenhouse gasses as well as human recreational opportunities including boating, paddling, fishing, hunting, birdwatching, hiking, and nature photography. Texas wetlands face intensifying challenges in the coming decades. Regulatory and legislative action should be forward-facing, anticipating effects of climate change, sea level rise, and urban expansion. Incorporating new technologies will allow for more timely and cost-efficient large-scale monitoring of wetland loss and gain. The residents of Texas are largely in support of active management of the state’s water resources; academic institutions, state and federal agencies, and conservation-minded private entities should work together to ensure the wetlands of Texas persist for wildlife and the generations to come.

Abstract The Reynolds Creek Experimental Watershed (RCEW) and Critical Zone Observatory (CZO), located south of the western Snake River Plain in the Intermountain West of the United States, is the site of over 60 years of research aimed at understanding integrated earth processes in a semi‐arid climate to aid sustainable use of environmental resources. Meteoric water lines (MWLs) are used to interpret hydrologic processes, though equilibrium and nonequilibrium processes affect the linear function and can reveal seasonal and climatological effects, necessitating the development of local meteoric water lines (LMWLs). At RCEW‐CZO, an RCEW LMWL was developed using non‐volume‐weighted, orthogonal regression with assumed error in both predictor and response variables from several years of precipitation (2015, 2017, 2019, 2020, and 2021) primarily at three different elevations (1203, 1585, and 2043 m). As most precipitation is evaporated or intercepted by vegetation in the driest months, an RCEW LMWL for groundwater recharge (RCEW LMWL‐GWR) was also developed using precipitation from the wettest months (November through April). The RCEW LMWL (δ2H = 7.41 × δ18O – 3.09) is different from the RCEW LMWL‐GWR (δ2H = 8.21 × δ18O + 9.95) and compares favorably to other LMWLs developed for the region and climate. Comparative surface, spring, and subsurface water datasets within the RCEW‐CZO are more similar to precipitation during the wettest months than dry months, illustrating that some semi‐arid hydrologic systems may most appropriately be compared to MWLs developed from precipitation only from the wettest season.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center’s:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3–4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Geologic, geomorphic, and climatic factors have been hypothesized to influence where streams dry, but hydrologists struggle to explain the temporal drivers of drying. Few hydrologists have isolated the role that vegetation plays in controlling the timing and location of stream drying in headwater streams. We present a distributed, fine-scale water balance through the seasonal recession and onset of stream drying by combining spatiotemporal observations and modeling of flow presence/absence, evapotranspiration, and groundwater inputs. Surface flow presence/absence was collected at fine spatial (~80 m) and temporal (15-min) scales at 25 locations in a headwater stream in southwestern Idaho, USA. Evapotranspiration losses were modeled at the same locations using the Simultaneous Heat and Water (SHAW) model. Groundwater inputs were estimated at four of the locations using a mixing model approach. In addition, we compared high-frequency, fine-resolution riparian normalized vegetation difference index (NDVI) with stream flow status. We found that the stream wetted and dried on a daily basis before seasonally drying, and daily drying occurred when evapotranspiration outputs exceeded groundwater inputs, typically during the hours of peak evapotranspiration. Riparian NDVI decreased when the stream dried, with a ~2-week lag between stream drying and response. Stream diel drying cycles reflect the groundwater and evapotranspiration balance, and riparian NDVI may improve stream drying predictions for groundwater-supported headwater streams.

The aim of this article is to examine the function of the archive in family autonovels and, in particular, in Mi abuelo y el dictador (2017) by the Mexican author César Tejeda. First of all, the characteristics of this phenomenon will be defined and, subsequently, will be applied to Tejeda's autonovel through a textual and paratextual analysis. Afterwards, the specific function of the archive in autonovels will be explained at length and, finally, the archives (letters, personal interviews, historical documents and places of memory) that are integrated into the book will be detailed. The result of this paper is to emphasize that the archive, which is the gap in itself (Didi-Huberman), turns the autobiographical family story into a truthful and, moreover, political manifestation.