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The complex dynamics of elastic fibers in viscous fluids are central to many biological and industrial systems. Fluid-structure interactions underlying these dynamics govern the shape and transport of flexible fibers, and understanding these interactions can help tune flow properties in applications such as microfluidic separation, printing and clogging. In this work, we use slender-body theory to study micromechanical dynamics that arise from the coupling between the elastic backbone of a fiber and the local straining flow that contributes to filament flipping and cross-streamline migration. The resulting transverse drift is unbiased in either direction in simple shear flow. However, a non-uniform shear rate results in bias towards regions of high shear, which we connect to the shape transitions during flips. We discover a depletion layer that forms near the boundaries of pressure-driven channel flow due to the competition between such a cross-streamline drift and steric exclusion from the walls. Finally, we develop scaling laws for the curvature of filaments during flip events, demonstrating the origin of the drift bias in non-uniform flows, and confirm this behavior from our simulations. Put together, these results shed light on the role of a local and dominant coupling between elasticity and viscous resistance in dictating long-term dynamics and transport of elastic fibers in confined flows.
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The TATA-box binding protein (TBP) is the sole transcription factor common in the initiation complexes of the three major eukaryotic RNA Polymerases (Pol I, II and III). Although TBP is central to transcription by the three RNA Pols in various species, the emergence of TBP paralogs throughout evolution has expanded the complexity in transcription initiation. Furthermore, recent studies have emerged that questioned the centrality of TBP in mammalian cells, particularly in Pol II transcription, but the role of TBP and its paralogs in Pol I transcription remains to be re-evaluated. In this report, we show that in murine embryonic stem cells TBP localizes onto Pol I promoters, whereas the TBP paralog TRF2 only weakly associates to the Spacer Promoter of rDNA, suggesting that it may not be able to replace TBP for Pol I transcription. Importantly, acute TBP depletion does not fully disrupt Pol I occupancy or activity on ribosomal RNA genes, but TBP binding in mitosis leads to efficient Pol I reactivation following cell division. These findings provide a more nuanced role for TBP in Pol I transcription in murine embryonic stem cells.
Assuntos
Mitose , Regiões Promotoras Genéticas , RNA Polimerase I , Proteína de Ligação a TATA-Box , Transcrição Gênica , Animais , RNA Polimerase I/metabolismo , RNA Polimerase I/genética , Proteína de Ligação a TATA-Box/metabolismo , Proteína de Ligação a TATA-Box/genética , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Ligação Proteica , DNA Ribossômico/genética , DNA Ribossômico/metabolismoRESUMO
Radiofrequency ablation for atrial fibrillation or atrial flutter is feasible in patients with deep brain stimulation but with extreme caution given the possibility of life-threatening complications.
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BACKGROUND: Brief intervention services provide rapid, mobile and flexible short-term delivery of interventions to resolve mental health crises. These interventions may provide an alternative pathway to the emergency department or in-patient psychiatric services for children and young people (CYP), presenting with an acute mental health condition. AIMS: To synthesise evidence on the effectiveness of brief interventions in improving mental health outcomes for CYP (0-17 years) presenting with an acute mental health condition. METHOD: A systematic literature search was conducted, and the studies' methodological quality was assessed. Five databases were searched for peer-reviewed articles between January 2000 and September 2022. RESULTS: We synthesised 30 articles on the effectiveness of brief interventions in the form of (a) crisis intervention, (b) integrated services, (c) group therapies, (d) individualised therapy, (e) parent-child dyadic therapy, (f) general services, (g) pharmacotherapy, (h) assessment services, (i) safety and risk planning and (j) in-hospital treatment, to improve outcomes for CYP with an acute mental health condition. Among included studies, one study was rated as providing a high level of evidence based on the National Health and Medical Research Council levels of evidence hierarchy scale, which was a crisis intervention showing a reduction in length of stay and return emergency department visits. Other studies, of moderate-quality evidence, described multimodal brief interventions that suggested beneficial effects. CONCLUSIONS: This review provides evidence to substantiate the benefits of brief interventions, in different settings, to reduce the burden of in-patient hospital and readmission rates to the emergency department.
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Background: Long term intervention services have proven to be effective in improving mental health (MH) outcomes and the quality of life for children and young people (CYP). Aim: To synthesize evidence on the effectiveness of long-term interventions in improving MH outcomes for CYP, 0-17 years, presenting with MH conditions. Methods: A systematic search was carried out and the methodological quality of included long term MH intervention studies were assessed. Six databases were searched for peer-reviewed articles between January 2000 and September 2022. Results: We found 30 studies that reported on the effectiveness of a range of long-term MH interventions in the form of (i) group therapy, (ii) multisystemic behavior therapy, (iii) general services, (iv) integrated services, (v) psychotherapy, (vi) intensive intervention services, (vii) comprehensive collaborative care, (viii) parent training, and (ix) home outreach service. Among the included studies, seven were rated as high level of evidence based on the National Health and Medical Research Council (NHMRC) levels of evidence hierarchy scale and seven were of moderate quality evidence. Others were rated as lower-quality evidence. Among the studies providing high quality evidence, most were reported for group therapy, general services, and psychotherapy studies demonstrating beneficial effects. Conclusion: This systematic review provides evidence to demonstrate the benefits of a range of long-term interventions, in a range of settings, can be effective in improving MH outcomes for CYP and their families. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022323324.
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PURPOSE: There is a lack of systematic solutions to manage supportive care issues in racial/ethnic minorities (REM) receiving treatment for cancer. We developed and implemented an electronic patient-reported outcome (ePRO)-driven symptom management tool led by oncology pharmacists in a majority-minority cancer center located in Southern California. This study was designed to evaluate the implementation outcomes of our multilevel intervention. METHODS: This was a prospective, pragmatic, implementation study conducted between July 2021 and June 2023. Newly diagnosed adult patients with cancer receiving intravenous anticancer therapies completed symptom screening using ePRO that consists of the Patient-Reported Outcomes Measurement Information System measures at each infusion visit during the study. ePRO results were presented to an oncologist pharmacist for personalized symptom management and treatment counseling. The RE-AIM framework was used to guide implementation outcomes. Differences in symptom trajectories and clinical outcomes between groups were tested using generalized estimating equations. RESULTS: We screened 388 patients of whom 250 were enrolled (acceptance rate: 64.4%), with 564 assessments being completed. The sample consisted of non-Hispanic White (NHW, 42.4%), Hispanic/Latinx (H/L, 30.8%), and non-Hispanic Asian (20.4%), with one (21.6%) of five participants preferring speaking Spanish. Compared with NHW, H/L participants had greater odds of reporting mild to severe pain interference (odds ratio [OR], 1.91 [95% CI, 1.18 to 3.08]; P = .008) and nausea and vomiting (OR, 2.08 [95% CI, 1.21 to 3.58]; P = .008), and higher rates of urgent care utilization (OR, 1.92 [95% CI, 1.04 to 3.61]; P = .04) within 30 days. Nausea and vomiting (n = 131, 23.2%), pain (n = 91, 16.1%), and fatigue (n = 72, 12.8%) were most likely to be intervened, with 90% of the participants expressing satisfaction across all visits. CONCLUSION: Our multilevel ePRO-driven intervention led by oncology pharmacists helps facilitate symptom assessments and management and potentially reduce health disparities among REM.
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BACKGROUND: Juvenile Nasopharyngeal Angiofibroma (JNA) is a fibrovascular tumor of the nasopharynx that classically presents in adolescent males. The reported mean age of onset is between 13 and 22 years old [1-6]. Significant androgen stimulation is hypothesized to explain the strong predisposition for JNA to present in young adolescent males. However, considerable variability in age at diagnosis exists with rare involvement of very young patients incongruent with typical male pubertal growth patterns. OBJECTIVE: The purpose of this systematic review is to identify cases of early-onset JNA (EOJNA), (defined as age < 10 years) in the literature and to examine the disease characteristics and treatments used in this patient group. A case of a 7 year old boy with EOJNA at our institution is also described and presented. METHODS: We searched Embase, Cochrane database and MEDLINE from 1996 to February 2021 for studies that reported cases of EOJNA. Relevant clinico-demographic data, disease severity and treatment outcomes were recorded and analyzed using descriptive statistics. We compared our findings with reported means for JNA in all ages. RESULTS: We identified 29 studies containing a total of 34 cases of EOJNA. The vast majority (31/34) of patients were males and the mean age of diagnosis was 8.15 years old. The most common presenting symptoms were nasal obstruction (65.2%) and epistaxis (60.9%). Patients were most commonly Radkowski stage II (39.4%) and III (39.4%). Primary treatment modalities included open surgery (66.7%), endoscopic surgery (24.2%), and radiotherapy (9.1%). Recurrence was evident in 30%. Radkowski stage and type of treatment did not differ significantly within the EOJNA group (p = 0.440 and p = 0.659, respectively). CONCLUSION: This systematic review suggests that rare cases of EOJNA have distinct disease characteristics. Patients in this cohort appeared to have more advanced disease and higher recurrence rates when compared with reported averages. We hope that this review prompts increased clinical awareness of this potentially more aggressive subtype of JNA. As more cases of EOJNA are reported, a more powered statistical analysis of this cohort would be feasible.