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Background: Female genital cutting is a culture bound ritual involving excision of the female genitalia. Little is known about nursing students' knowledge and perceptions of female genital cutting and no studies using simulation to teach this topic exist., Objective: The aim of this study was to examine the impact of a dramatization simulation on nursing students' knowledge about and perceptions of female genital cutting., Design: A quasi-experimental pretest posttest study with a convenience sample., Setting: Two Bachelor of Nursing schools in Northeast Ohio, United States., Participants: 35 third year undergraduate students., Methods: Students were divided into an intervention group (n = 14) and a wait list control group (n = 21). The intervention group took a pre-test, did a reading assignment and then attended a virtual, dramatization simulation session with a standardized patient; a Muslim woman with a personal history of female genital cutting. They took the posttest within the next week. The control group took the pretest, did the reading assignment, and then took the posttest, followed by the simulation. The survey instrument used for pretest and posttest was the Knowledge, Perceptions, and Practice Questionnaire on Female Genital Cutting for Healthcare Professionals in the United States. Debriefing was a critical part of the simulation., Results: The knowledge of female genital cutting of the nursing students in the intervention group increased more than that of the students in the control group (change score 3.57 and 2.05 respectively). Students' perceptions of female genital cutting were not significantly changed by intervention type., Conclusion: This study was the first of its kind to measure nursing students' knowledge and perceptions about female genital cutting before and after a dramatization simulation. A standardized patient dramatization simulation including focused debriefing may be an effective education strategy to teach nursing students about female genital cutting., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Female genital cutting/mutilation (FGC/M) is a ritual to remove any or all of the external female genitalia. Educational strategies regarding the teaching of FGC/M for nursing students are scarce. The focus of this article is to describe the development, implementation, and evaluation of a virtual, FGC/M-related dramatization simulation with a standardized patient (SP)., Methods: This educational intervention used an East African immigrant woman as the SP with 35 undergraduate nursing students in two nursing schools in the Midwest United States., Results: Participants appraised the simulation as an effective way to teach and learn about FGC/M. Debriefing was a key part of the simulation., Discussion: Students felt the simulation was novel and engaging for a highly sensitive topic. The SP thought the virtual setting made it more comfortable for her to reveal sensitive facts. The researchers confirmed that the simulation required extensive time commitment to develop, critique, and implement.

Single-cell RNA sequencing (scRNA-seq) revolutionized our understanding of disease biology. The promise it presents to also transform translational research requires highly standardized and robust software workflows. Here, we present the toolkit Besca , which streamlines scRNA-seq analyses and their use to deconvolute bulk RNA-seq data according to current best practices. Beyond a standard workflow covering quality control, filtering, and clustering, two complementary Besca modules, utilizing hierarchical cell signatures and supervised machine learning, automate cell annotation and provide harmonized nomenclatures. Subsequently, the gene expression profiles can be employed to estimate cell type proportions in bulk transcriptomics data. Using multiple, diverse scRNA-seq datasets, some stemming from highly heterogeneous tumor tissue, we show how Besca aids acceleration, interoperability, reusability and interpretability of scRNA-seq data analyses, meeting crucial demands in translational research and beyond., (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

The liver is a major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and nonredundant action of two innate lymphocyte subpopulations, conventional natural killer cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s), is essential for antimetastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 controls metastatic seeding, whereas cNKs restrain outgrowth. Whereas the killing capacity of trILC1s was not affected by the metastatic microenvironment, the phenotype and function of cNK cells were affected in a cancer type-specific fashion. Thus, individual cancer cell lines orchestrate the emergence of unique cNK subsets, which respond differently to tumor-derived factors. Our findings will contribute to the development of therapies for liver metastasis involving hepatic innate cells., Competing Interests: The authors declare no competing interest.

Background: Over 500,000 women and girls in the U.S. are at risk for female genital cutting/mutilation, (FGC/M) because their cultural heritage is from countries where FGC/M is prevalent. Nurses lack knowledge about FGC/M, making them less likely to provide culturally congruent care. Little is known about FGC/M-related information in nursing school curriculums., Methods: A total of 403 schools of nursing (SONs) responded to an anonymous online survey to identify the extent, placement, and educational approaches regarding FGC/M found in curricular content in nursing schools in the U.S., Results: Fifty-seven percent of respondents did not know if nurses cared for FGC/M-affected women in the region where their nursing school was located. Only 27% of responding schools indicated FGC/M was taught in their curriculums, mostly in undergraduate programs, and primarily during classroom lectures, and rarely by simulation. SONs that were aware that nurses in their region provided care to women and girls at risk for FGC/M were more likely to have content on FGC/M in their curriculums., Conclusion: Though respondents indicated that this topic is important to global nursing education, it appears that few U.S. nursing students are learning to provide culturally congruent care to women and girls at risk for FGC/M. It is vital that nurse educators include this topic in appropriate places in the curriculum, so that students learn the unique healthcare needs of this population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Overtly self-reactive T cells are removed during thymic selection. However, it has been recently established that T cell self-reactivity promotes protective immune responses. Apparently, the level of self-reactivity of mature T cells must be tightly balanced. Our mathematical model and experimental data show that the dynamic regulation of CD4- and CD8-LCK coupling establish the self-reactivity of the peripheral T cell pool. The stoichiometry of the interaction between CD8 and LCK, but not between CD4 and LCK, substantially increases upon T cell maturation. As a result, peripheral CD8 + T cells are more self-reactive than CD4 + T cells. The different levels of self-reactivity of mature CD8 + and CD4 + T cells likely reflect the unique roles of these subsets in immunity. These results indicate that the evolutionary selection pressure tuned the CD4-LCK and CD8-LCK stoichiometries, as they represent the unique parts of the proximal T cell receptor (TCR) signaling pathway, which differ between CD4 + and CD8 + T cells., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Designing educational activities that engage health profession students' interest in community-based learning is challenging. University faculty channeled concerns about regional trends in cardiovascular disease among adolescents into activities that linked students' foundational knowledge to critical application experiences., Method: Between 2013 and 2017, university faculty partnered with a local health system and a public high school to develop a sustainable health promotion plan for the school. The university component involved activities that students implemented as part of their community clinical experiences., Results: Participant results and feedback were overwhelmingly positive and affirmed that linking learning to real-world concerns made preventive health care concepts interesting and easier to grasp., Conclusion: Educational activities that involve neighboring stakeholders is a creative and meaningful way to provide engaging learning experiences for future health professionals while contributing to authentic solutions within a community-based partnership. [J Nurs Educ. 2019;58(8):485-487.]., (Copyright 2019, SLACK Incorporated.)

In the absence of extensive transcription control mechanisms the pathogenic parasite Trypanosoma brucei crucially depends on translation regulation to orchestrate gene expression. However, molecular insight into regulating protein biosynthesis is sparse. Here we analyze the small non-coding RNA (ncRNA) interactome of ribosomes in T. brucei during different growth conditions and life stages. Ribosome-associated ncRNAs have recently been recognized as unprecedented regulators of ribosome functions. Our data show that the tRNA Thr 3´half is produced during nutrient deprivation and becomes one of the most abundant tRNA-derived RNA fragments (tdRs). tRNA Thr halves associate with ribosomes and polysomes and stimulate translation by facilitating mRNA loading during stress recovery once starvation conditions ceased. Blocking or depleting the endogenous tRNA Thr halves mitigates this stimulatory effect both in vivo and in vitro. T. brucei and its close relatives lack the well-described mammalian enzymes for tRNA half processing, thus hinting at a unique tdR biogenesis in these parasites.

Cancer is the second leading cause of death in Switzerland. Patients who have been diagnosed with colorectal carcinoma and received curative surgical R0-Resection frequently relapse or develop metastases in the first 2-3 years postoperatively. With timely detection through appropriate aftercare, some of these patients could potentially be cured. In order to optimize follow-up adherence, we implemented a study environment based on an app, which reminds patients to schedule their follow-up appointments timely with their GP or specialist. In addition, the study environment comprises a central server to collect pseudonomized study data regarding follow-up compliance. The next step will be a study to evaluate the potential impact of such an app. We present the outline of the planned study.

Conduct disorder (CD) is a psychiatric disorder of childhood and adolescence which has been linked to deficient emotion processing and regulation. The behavioral and neuronal correlates targeting the interaction of emotion processing and response inhibition are still under investigation. Whole-brain event-related fMRI was applied during an affective Stroop task in 39 adolescents with CD and 39 typically developing adolescents (TD). Participants were presented with an emotional stimulus (negative/neutral) followed by a Stroop task with varying cognitive load (congruent/incongruent/blank trials). fMRI analysis included standard preprocessing, region of interest analyses (amygdala, insula, ventromedial prefrontal cortex) and whole-brain analyses based on a 2( group ) × 2( emotion ) × 3( task ) full-factorial ANOVA. Adolescents with CD made significantly more errors, while reaction times did not significantly differ compared to TD. Additionally, we observed a lack of downregulation of left amygdala activity in response to incongruent trials and increased anterior insula activity for CD relative to TD during affective Stroop task processing [cluster-level family-wise error-corrected ( p < 0.05)]. Even though no three-way interaction ( group × emotion × task ) interaction was detected, the findings presented still provide evidence for altered neuronal underpinnings of the interaction of emotion processing and response inhibition in CD. Moreover, our results may corroborate previous evidence of emotion dysregulation as a core dysfunction in CD. Future studies shall focus on investigating the interaction of emotion processing and response inhibition in CD subgroups (e.g., variations in callous-unemotional traits, impulsivity, or anxiety).

Regulation of gene expression at the translational level allows rapid adaptation of cellular proteomes to quickly changing environmental conditions and is thus central for prokaryotic organisms. Small non-coding RNAs (sRNAs) have been reported to effectively orchestrate translation control in bacteria and archaea mainly by targeting mRNAs by partial base complementarity. Here we report an unprecedented mechanism how sRNAs are capable of modulating protein biosynthesis in the halophilic archaeon Haloferax volcanii. By analyzing the ribosome-associated ncRNAs (rancRNAs) under different stress conditions we identified an intergenic sRNA, termed rancRNA&#95;s194, that is primarily expressed during exponential growth under all tested conditions. By interaction with the ribosome rancRNA&#95;s194 inhibits peptide bond formation and protein synthesis in vitro but appears to target a specific mRNA in vivo. The respective knock-out strain shows a reduced lag phase in media containing xylose as sole carbon source and outcompetes the wildtype cells under these conditions. Mass spectrometry, polysome profiling and mRNA binding competition experiments suggest that rancRNA&#95;s194 prevents the cstA mRNA from being efficiently translated by H. volcanii ribosomes. These findings enlarge the regulatory repertoire of archaeal sRNAs in modulating post-transcriptional gene expression.

Early dysfunction of cortical motor neurons may underlie the initiation of amyotrophic lateral sclerosis (ALS). As such, the cortex represents a critical area of ALS research and a promising therapeutic target. In the current study, human cortical-derived neural progenitor cells engineered to secrete glial cell line-derived neurotrophic factor (GDNF) were transplanted into the SOD1 G93A ALS rat cortex, where they migrated, matured into astrocytes, and released GDNF. This protected motor neurons, delayed disease pathology and extended survival of the animals. These same cells injected into the cortex of cynomolgus macaques survived and showed robust GDNF expression without adverse effects. Together this data suggests that introducing cortical astrocytes releasing GDNF represents a novel promising approach to treating ALS. Stem Cells 2018;36:1122-1131., (© 2018 The Authors STEM CELLS published by Wiley Periodicals, Inc.)

Posttranscriptional processing of RNA molecules is a common strategy to enlarge the structural and functional repertoire of RNomes observed in all 3 domains of life. Fragmentation of RNA molecules of basically all functional classes has been reported to yield smaller non-protein coding RNAs (ncRNAs) that typically possess different roles compared with their parental transcripts. Here we show that a valine tRNA-derived fragment (Val-tRF) that is produced under certain stress conditions in the halophilic archaeon Haloferax volcanii is capable of binding to the small ribosomal subunit. As a consequence of Val-tRF binding mRNA is displaced from the initiation complex which results in global translation attenuation in vivo and in vitro. The fact that the archaeal Val-tRF also inhibits eukaryal as well as bacterial protein biosynthesis implies a functionally conserved mode of action. While tRFs and tRNA halves have been amply identified in recent RNA-seq project, Val-tRF described herein represents one of the first functionally characterized tRNA processing products to date.

Welcome Day, one specific day in the life of Hartville Migrant Ministry (HMM), a faith-based ministry in Ohio, illustrates the organization's vision, mission, and community collaboration. Migrant and seasonal farm workers, the Migrant Head Start program, HMM and Welcome Day, interprofessional collaboration, and Malone University School of Nursing faculty and students support are discussed. Programs and activities presented here could be reproduced in other communities.

Introduction: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology., Methods: Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed., Results: All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum., Conclusions: Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Background: Concussion injury is the most common form of traumatic brain injury (TBI). How recurrent concussions alter long-term outcomes is poorly understood, especially as related to the development of neurodegenerative disease. We evaluated the functional and pathological consequences of repeated TBI over time in wild type (WT) rats as well as rats harboring the human SOD1 mutation ("SOD1"), a model of familial amyotrophic lateral sclerosis (ALS)., Methods: A total of 42 rats, 26 WT and 16 SOD1, were examined over a study period of 25 weeks (or endpoint). At postnatal day 60, 20 WT and 7 SOD1 rats were exposed to mild, bilateral TBI once per week for either 2 weeks (2×TBI) or 5 weeks (5×TBI) using a controlled cortical impact device. Six WT and nine SOD1 rats underwent sham injury with anesthesia alone. Twenty WT rats were euthanized at 12 weeks after first injury and six WT rats were euthanized at 25 weeks after first injury. SOD1 rats were euthanized when they reached ALS disease endpoint. Weekly body weights and behavioral assessments were performed. Tauopathy in brain tissue was analyzed using immunohistochemistry., Results: 2XTBI injured rats initially demonstrated recovery of motor function but failed to recover to baseline within the 12-week study period. Relative to both 2XTBI and sham controls, 5XTBI rats demonstrated significant deficits that persisted over the 12-week period. SOD1 5XTBI rats reached a peak body weight earlier than sham SOD1 rats, indicating earlier onset of the ALS phenotype. Histologic examination of brain tissue revealed that, in contrast with sham controls, SOD1 and WT TBI rats demonstrated cortical and corpus collosum thinning and tauopathy, which increased over time., Conclusions: Unlike previous models of repeat brain injury, which demonstrate only transient deficits in motor function, our concussion model of repeat, mild, bilateral TBI induced long-lasting deficits in motor function, decreased cortical thickness, shrinkage of the corpus callosum, increased brain tauopathy, and earlier onset of ALS symptoms in SOD1 rats. This model may allow for a greater understanding of the complex relationship between TBI and neurodegenerative diseases and provides a potential method for testing novel therapeutic strategies.

Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v) in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC) Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis.

Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates with T helper (Th)1 differentiation at both high and low doses of antigen. In contrast, follicular helper T cell (TFH) effectors are generated after priming with high, intermediate, and low affinity ligand. Unexpectedly, memory T cells generated after priming with very low affinity antigen remain impaired in their ability to generate secondary Th1 effectors, despite being recalled with high affinity antigen. These data challenge the view that only strongly stimulated CD4 T cells are capable of differentiating into the TFH and memory T-cell compartments and reveal that differential strength of stimulation during primary T-cell activation imprints unique and long lasting T-cell differentiation programs.

LY2228820 dimesylate is a highly selective small molecule inhibitor of p38α and p38β mitogen-activated protein kinases (MAPKs) that is currently under clinical investigation for human malignancies. p38 MAPK is implicated in a wide range of biological processes, in particular those that support tumorigenesis. One such process, angiogenesis, is required for tumor growth and metastasis, and many new cancer therapies are therefore directed against the tumor vasculature. Using an in vitro co-culture endothelial cord formation assay, a surrogate of angiogenesis, we investigated the role of p38 MAPK in growth factor- and tumor-driven angiogenesis using LY2228820 dimesylate treatment and by shRNA gene knockdown. p38 MAPK was activated in endothelial cells upon growth factor stimulation, with inhibition by LY2228820 dimesylate treatment causing a significant decrease in VEGF-, bFGF-, EGF-, and IL-6-induced endothelial cord formation and an even more dramatic decrease in tumor-driven cord formation. In addition to involvement in downstream cytokine signaling, p38 MAPK was important for VEGF, bFGF, EGF, IL-6, and other proangiogenic cytokine secretion in stromal and tumor cells. LY2228820 dimesylate results were substantiated using p38α MAPK-specific shRNA and shRNA against the downstream p38 MAPK effectors MAPKAPK-2 and HSP27. Using in vivo models of functional neoangiogenesis, LY2228820 dimesylate treatment reduced hemoglobin content in a plug assay and decreased VEGF-A-stimulated vascularization in a mouse ear model. Thus, p38α MAPK is implicated in tumor angiogenesis through direct tumoral effects and through reduction of proangiogenic cytokine secretion via the microenvironment.

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C(-/-) mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C(-/-) mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C(-/-) C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C(-/-) mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3(rd) ventricle in JAM-C(-/-) C57BL/6 mice. Taken together, our study suggests that JAM-C(-/-) C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.

The median urinary iodine concentration (UI) in school-aged children is recommended for assessment of iodine nutrition in populations. If the median UI is adequate in school-aged children, it is usually assumed iodine intakes are also adequate in the remaining population, including pregnant women. But iodine requirements sharply increase during pregnancy. In this study, our aim was to measure UI in pairs of pregnant women and their school-aged children from the same family, who were sharing meals, to directly assess whether a household food basket that supplies adequate iodine to school-aged children also meets the needs of pregnant women. UI was measured in spot urine samples from pairs (n = 302) of healthy pregnant mothers and their school-aged children in metropolitan Bangkok, Thailand. A dietary questionnaire was completed. The UI [median (range)] in the pregnant women {108 (11-558) microg/L [0.85 (0.086-4.41) micromol/L]} were lower than those of their school-aged children {200 (25-835) microg/L [1.58 (0.20-6.52) micromol/L]} (P < 0.001), indicating optimal iodine status in the children but mild-to-moderate iodine deficiency in their pregnant mothers. The estimated iodine intakes in the 2 groups were in the range of 130-170 microg/d. There was a modest positive correlation between UI in the pairs (r = 0.253; P < 0.01). A higher frequency of seafood meals was a significant predictor of UI in both groups, but household use of iodized salt was not. These data suggest the median UI in school-aged children should not be used as a surrogate for monitoring iodine status in pregnancy in central Thailand; pregnant women should be directly monitored.