Zika virus (ZIKV) has been associated with several neurological complications in adult patients.
We used a mouse model deficient in TRIF and IPS-1 adaptor proteins, which are involved in type I ...interferon production, to study the role of microglia during brain infection by ZIKV. Young adult mice were infected intravenously with the contemporary ZIKV strain PRVABC59 (1 × 10
PFUs/100 µL).
Infected mice did not present overt clinical signs of the disease nor body weight loss compared with noninfected animals. However, mice exhibited a viremia and a brain viral load that were maximal (1.3 × 10
genome copies/mL and 9.8 × 10
genome copies/g of brain) on days 3 and 7 post-infection (p.i.), respectively. Immunohistochemistry analysis showed that ZIKV antigens were distributed in several regions of the brain, especially the dorsal hippocampus. The number of Iba1
/TMEM119
microglia remained similar in infected versus noninfected mice, but their cell body and arborization areas significantly increased in the stratum radiatum and stratum lacunosum-moleculare layers of the dorsal hippocampus cornu ammoni (CA)1, indicating a reactive state. Ultrastructural analyses also revealed that microglia displayed increased phagocytic activities and extracellular digestion of degraded elements during infection. Mice pharmacologically depleted in microglia with PLX5622 presented a higher brain viral load compared to untreated group (2.8 × 10
versus 8.5 × 10
genome copies/g of brain on day 10 p.i.) as well as an increased number of ZIKV antigens labeled with immunogold in the cytoplasm and endoplasmic reticulum of neurons and astrocytes indicating an enhanced viral replication. Furthermore, endosomes of astrocytes contained nanogold particles together with digested materials, suggesting a compensatory phagocytic activity upon microglial depletion.
These results indicate that microglia are involved in the control of ZIKV replication and/or its elimination in the brain. After depletion of microglia, the removal of ZIKV-infected cells by phagocytosis could be partly compensated by astrocytes.
Detection of Zika virus (ZIKV) in the central nervous system (CNS) is a critical step when studying the pathogenesis of the infection in animal models. Both viral load determination and ...immunohistochemistry (IHC) staining are useful methods to quantitatively and qualitatively characterize viral infections in target tissues. Here, we describe viral RNA load determination by droplet digital PCR as well as protein detection by polymer-based IHC as effective techniques to quantify and localize ZIKV in the CNS of mice.
Patient safety has become an important aspect of national health care initiatives. The purpose of this evaluation was to measure the impact of a patient safety education series for students enrolled ...in a nurse anesthesia program. Baseline surveys that measured patient safety competencies across three domains, attitudes, skills and knowledge, were administered to the students. A patient safety education series was delivered to the cohort and the survey was then readministered. Mean scores were compared using independent samples t tests. Attitude scores did not change from baseline to posttest. Participants scored higher on posttest means for both the patient safety skills and knowledge domains. Incorporating patient safety content into the nurse anesthesia master's degree curriculum may enhance clinicians' skills and knowledge related to patient safety, and the addition of a patient safety curriculum is important during the formative education process.
Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution
. Most clinical strategies rely on histopathological stratification of tumour ...subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm
tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.
Checkpoint inhibitors directed against programmed death receptor 1 (PD-1) and its ligand (PD-L1) changed the treatment of advanced lung non–small cell carcinomas. The decision to treat patients is ...influenced by PD-L1 expression by tumor cells, but evidence indicates that this staining is heterogenous within a tumor. As PD-L1 staining is tested mostly on biopsies, false negative results can occur due to sampling issues. The clinical impact of this heterogeneity has not been established. We selected 241 patients who underwent pulmonary resection for adenocarcinoma. Tissue microarrays were constructed with five 1 mm cores representative of the histologic patterns observed in each tumor and stained for PD-L1. For each core, the histologic pattern and the percentage of PD-L1 positive tumor cells were noted. Staining heterogeneity was defined as cases with both positive and negative cores at positivity thresholds of 1%, 10%, and 50% of tumor cells. At the 50% cut-off, 37.8% of patients were PD-L1 positive, whereas 22.4% showed staining heterogeneity. Among patients with 1 negative core, 26.5% also had a positive core and could have been misclassified based on 1 biopsy. Mean staining of PD-L1 was higher in solid (47.9%) and micropapillary (24.2%) patterns and was lower in acinar (14.1%), papillary (3.4%), and lepidic (6.4%) architectures. A significant proportion of patients presented a heterogenous staining for PD-L1. A total of 26.5% of patients negative on 1 core turned out to be positive on another core, which raises the consideration of rebiopsy, in particular when lepidic, acinar, or papillary patterns are observed on a biopsy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
7.
Refocusing Research Priorities in Schools of Nursing Kulage, Kristine M.; Ardizzone, Laura; Enlow, William ...
Journal of professional nursing,
July-August 2013, 2013 Jul-Aug, 2013-7-00, 20130701, Letnik:
29, Številka:
4
Journal Article
Recenzirano
It is critical for schools of nursing to periodically reassess their scholarly programs to ensure that their conceptual framework and approaches address current challenges and enhance productivity. ...This article describes the process undertaken at Columbia University School of Nursing to evaluate scholarly enterprise so that it remains relevant and responsive to changing trends and to revise our research conceptual model to be reflective of the foci of our clinicians and researchers. As part of a larger strategic initiative, a two-phase Research Excellence Planning and Implementation Workgroup was convened, consisting of a broad representation of faculty and administrative staff, with an overall goal of expanding scholarly capacity. During Phase I, members developed measurable outcomes and tactics and revised the school's conceptual research model. In Phase II, the workgroup implemented and monitored tactics and presented final recommendations to the dean. To measure progress, faculty members completed a survey to establish baseline scholarship and collaboration with results indicating room for growth in interdisciplinary and inter-institutional collaboration. Ongoing assessment of outcomes includes Web-based tracking of scholarly activities and follow-up surveys to monitor expansion of faculty collaboration. We recommend this process to other schools committed to sustainable, increasingly relevant scholarship.
ULTRANOX 626 diphosphite and its oxidation product and WESTON 618 diphosphite were analyzed by electron ionization Fourier transform ion cyclotron resonance mass spectrometry. The method offers an ...accurate means for detecting nonvolatile phosphite additives at typical concentration in solid polymers.
Depuis sa réémergence durant l'épidémie de 2013-2017 dans les régions du Pacifique et des Amériques, le virus Zika a été associé à plusieurs complications neurologiques chez l'adulte. L'immunité ...innée représente une composante importante de la réponse immunitaire au sein du système nerveux central (SNC). Nous avons donc postulé que les microglies, macrophages résidents du SNC, jouent un rôle actif dans le développement de la réponse initiale à l'infection du cerveau mature par le virus Zika. Nous avons utilisé un modèle murin non létal, déficient pour des composantes de l'immunité innée, pour étudier le rôle des microglies dans la pathogénèse et la réponse immunitaire lors de l'infection du SNC. Les souris infectées présentaient une virémie et une charge virale cérébrale élevées sans manifestations cliniques de l'infection. Une analyse immunohistochimique a montré que le virus Zika était distribué dans plusieurs régions du cerveau, particulièrement dans l'hippocampe dorsal. Dans cette région, le nombre de microglies est demeuré stable après l'infection, mais elles montraient des caractéristiques morphologiques compatibles avec un état de réactivité. Une analyse ultrastructurelle en microscopie électronique a révélé que les microglies présentaient une activité phagocytaire et une digestion extracellulaire accrues durant l'infection. La déplétion pharmacologique des microglies a provoqué une augmentation de la réplication virale et les astrocytes présentaient une activité phagocytaire compensatoire. Dans l'ensemble, ces résultats montrent que les microglies sont impliquées dans le contrôle de la réplication du virus Zika et dans son élimination phagocytaire au sein du SNC de souris jeunes adultes immunodéficientes.
Since its re-emergence during the 2013-2017 epidemic across the Pacific and the Americas, Zika virus has been associated with several neurological complications in adults. Because innate immunity is an important component of the immune response within the central nervous system (CNS), we postulated that microglia, the resident macrophages of the CNS, play an active role in the development of the initial response to infection of the mature brain with Zika virus. We used a non-lethal mouse model deficient in components of innate immunity to study the role of microglia in the pathogenesis and immune response of Zika virus infection of the CNS. Infected mice developed elevated viremia and brain viral load without showing clinical signs of infection. Immunohistochemical analysis showed that Zika virus was distributed in several regions of the brain, predominantly in the dorsal hippocampus. In this region, the number of microglia remained steady after infection with Zika virus, but microglia adopted morphological characteristics consistent with a state of reactivity. Ultrastructural analysis by electron microscopy revealed that microglia exhibited increased phagocytic activity and extracellular digestion during infection. Pharmacological depletion of microglia caused an increase in viral replication and astrocytes exhibited compensatory phagocytic activity. Taken together, these results show that microglia are involved in the control of Zika virus replication and its phagocytic elimination within the brain of immunodeficient young adult mice.
This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the ...Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009‐2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.
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