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While initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine-rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance following induction is often utilized. Thus, the open-label, randomized phase II ECOG-ACRIN Cancer Research Group E1411 trial was designed to test two questions: 1) Does addition of bortezomib to BR induction (BVR) and/or 2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012-2016, 373 previously untreated patients, 87% ≥ 60 years old, were enrolled in this trial. At a median follow up of 7.5 years, there is no difference in the median PFS of BR compared to BVR (5.5 yrs vs. 6.4 yrs, HR 0.90, 90% CI 0.70, 1.16). There were no unexpected additional toxicities with BVR treatment compared to BR, with no impact on total dose/duration of treatment received. Independent of the induction treatment, addition of lenalidomide to rituximab did not significantly improve PFS, with median PFS in R vs LR (5.9 yrs vs 7.2 yrs, HR 0.84 90% CI 0.62, 1.15). The majority of patients completed the planned 24 cycles of LR at the scheduled dose. In summary, adding bortezomib to BR induction does not prolong PFS in treatment-naïve MCL, and LR maintenance was not associated with longer PFS compared with rituximab alone following BR. Nonetheless, the > 5 year median PFS outcomes in this prospective cooperative group trial indicate the efficacy of BR followed by rituximab maintenance as highly effective initial therapy for older MCL patients. (NCT01415752).
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Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome resulting from a reciprocal translocation between chromosomes 9 and 22 [t9;22] that gives rise to a BCR::ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase in developed countries. Tyrosine kinase inhibitor (TKI) therapy is a highly effective treatment option for patients with chronic phase-CML. The primary goal of TKI therapy in patients with chronic phase-CML is to prevent disease progression to accelerated phase-CML or blast phase-CML. Discontinuation of TKI therapy with careful monitoring is feasible in selected patients. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase-CML.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Humanos , Crise Blástica/induzido quimicamente , Crise Blástica/tratamento farmacológico , Crise Blástica/genética , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Proteínas de Fusão bcr-abl/genéticaRESUMO
BACKGROUND: Epithelial ingrowth is a rare but potentially sight-threatening complication caused by the invasion of corneal or conjunctival epithelial cells into the eye during ocular surgeries. DMEK is emerging as a widely used surgery for endothelial keratoplasty with its improved safety profile. We describe a case of epithelial ingrowth in the graft-host interface after uneventful DMEK associated with vitreous prolapse in the anterior chamber. CASE PRESENTATION: An 81-year-old female with Fuchs endothelial dystrophy underwent DMEK for corneal decompensation following cataract surgery. During the DMEK procedure, vitreous prolapse was observed around the intraocular lens (IOL). Her early postoperative course was unremarkable, but a dense paracentral interface opacity was observed during the 3-month follow-up. The area of epithelial ingrowth was imaged with optical coherence tomography (OCT) as a uniform nodule with a discrete increase in interface hyperreflectivity. A low-energy YAG laser was applied to remove the opacity. She maintained good vision and clear cornea without reoccurrence after treatment. CONCLUSIONS: We propose that, in addition to the introduction of epithelial cells during surgery, vitreous retention in the anterior chamber may be a risk factor by providing a scaffold that potentially aggravates epithelial ingrowth in DMEK. Our case demonstrated that early YAG intervention may disrupt interface epithelial cell growth, and the transmitted laser energy may fragment the scaffold vitreous noninvasively.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Feminino , Idoso de 80 Anos ou mais , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Complicações Pós-Operatórias/cirurgia , Distrofia Endotelial de Fuchs/cirurgia , Transtornos da Visão , Prolapso , Estudos RetrospectivosRESUMO
The treatment of spinal infections is not well defined, and a cursory review of the literature can lead to conflicting treatment strategies. To add to the complexity, infections can include primary infection of the spine, infection secondary to another primary source, and postoperative infections including epidural abscesses, discitis, osteomyelitis, paraspinal soft-tissue infections, or any combination. Furthermore, differing opinions often exist within the medical and surgical communities regarding the outcomes and effectiveness of varying treatment strategies. Given the paucity of defined treatment protocols and long-term follow-up, it is important to develop multidisciplinary treatment teams and treatment strategies. This, along with defined protocols for the treatment of varying infections, can provide the data needed for improved treatment of spinal infections.
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Discite , Abscesso Epidural , Osteomielite , Humanos , Discite/diagnóstico , Discite/cirurgia , Abscesso Epidural/diagnóstico , Abscesso Epidural/cirurgia , Imageamento por Ressonância Magnética , Osteomielite/diagnóstico , Osteomielite/terapia , Coluna VertebralRESUMO
Localization based on single-line lidar is widely used in various robotics applications, such as warehousing, service, transit, and construction, due to its high accuracy, cost-effectiveness, and minimal computational requirements. However, challenges such as LiDAR degeneration and frequent map changes persist in hindering its broader adoption. To address these challenges, we introduce the Contribution Sampling and Map-Updating Localization (CSMUL) algorithm, which incorporates weighted contribution sampling and dynamic map-updating methods for robustness enhancement. The weighted contribution sampling method assigns weights to each map point based on the constraints within degenerate environments, significantly improving localization robustness under such conditions. Concurrently, the algorithm detects and updates anomalies in the map in real time, addressing issues related to localization drift and failure when the map changes. The experimental results from real-world deployments demonstrate that our CSMUL algorithm achieves enhanced robustness and superior accuracy in both degenerate scenarios and dynamic map conditions. Additionally, it facilitates real-time map adjustments and ensures continuous positioning, catering to the needs of dynamic environments.
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Triple-negative breast cancer (TNBC) is characterized by the absence of the estrogen receptor, progesterone receptor, and receptor tyrosine kinase HER2 expression. Due to the limited number of FDA-approved targeted therapies for TNBC, there is an ongoing need to understand the molecular underpinnings of TNBC for the development of novel combinatorial treatment strategies. This study evaluated the role of the MerTK receptor tyrosine kinase on proliferation and invasion/metastatic potential in TNBC. Immunohistochemical analysis demonstrated MerTK expression in 58% of patient-derived TNBC xenografts. The stable overexpression of MerTK in human TNBC cell lines induced an increase in proliferation rates, robust in vivo tumor growth, heightened migration/invasion potential, and enhanced lung metastases. NanoString nCounter analysis of MerTK-overexpressing SUM102 cells (SUM102-MerTK) revealed upregulation of several signaling pathways, which ultimately drive cell cycle progression, reduce apoptosis, and enhance cell survival. Proteomic profiling indicated increased endoglin (ENG) production in SUM102-MerTK clones, suggesting that MerTK creates a conducive environment for increased proliferative and metastatic activity via elevated ENG expression. To determine ENG's role in increasing proliferation and/or metastatic potential, we knocked out ENG in a SUM102-MerTK clone with CRISPR technology. Although this ENG knockout clone exhibited similar in vivo growth to the parental SUM102-MerTK clone, lung metastasis numbers were significantly decreased ~4-fold, indicating that MerTK enhances invasion and metastasis through ENG. Our data suggest that MerTK regulates a unique proliferative signature in TNBC, promoting robust tumor growth and increased metastatic potential through ENG upregulation. Targeting MerTK and ENG simultaneously may provide a novel therapeutic approach for TNBC patients.
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Proliferação de Células , Neoplasias de Mama Triplo Negativas , c-Mer Tirosina Quinase , Humanos , c-Mer Tirosina Quinase/metabolismo , c-Mer Tirosina Quinase/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Animais , Feminino , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Endoglina/metabolismo , Endoglina/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Transdução de Sinais , Apoptose/genéticaRESUMO
BACKGROUND: Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events. PURPOSE: The aims of this review are to evaluate the evidence for efficacy of second- and third-line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review.
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BACKGROUND: Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades. PURPOSE: The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.
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We conducted a retrospective study to assess performance of provider-selected antibiotic indication (PSI) in identifying hospitalized adults with community-acquired pneumonia. PSI showed moderate sensitivity (64.4%) and high specificity (96.3%). PSI has potential utility for targeted real-time antibiotic stewardship interventions, though future research should investigate methods to improve sensitivity.
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OBJECTIVE: In recent years, the academic medicine community has produced numerous statements and calls to action condemning racism. Though health equity work examining health disparities has expanded, few studies specifically name racism as an operational construct. As emergency departments serve a high proportion of patients with social and economic disadvantage rooted in structural racism, it is critically important that racism be a focus of our academic discourse. This study examines the frequency at which four prominent emergency medicine journals, Annals of Emergency Medicine, Academic Emergency Medicine, the American Journal of Emergency Medicine, and the Western Journal of Emergency Medicine, publish on health disparities and racism. METHODS: This is a descriptive analysis measuring the frequency of publications on health disparities and racism in U.S.-based emergency medicine journals from 2014 to 2021. The search strategies for the concepts of "racism" and "health disparities" used a combination of MeSH and keywords. These search strategies were developed based on prior literature and the MEDLINE/PubMed Health Disparities and Minority Health Search Strategy. Articles identified through the PubMed search were then reviewed by two authors for final inclusion. RESULTS: Since 2014, a total of 6248 articles were published by the four emergency medicine journals over the 8-year study period. Of those, 82 research papers that focused on health disparities were identified and only 16 that focused on racism. Most emergency medicine publications on racism and health disparities were in 2021. CONCLUSIONS: Our findings suggest that the national discourse on racism and calls to action within emergency medicine were followed by an increase in publications on health disparities and racism. Continued investigation is needed to evaluate these trends moving forward.
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Medicina de Emergência , Publicações Periódicas como Assunto , Racismo , Humanos , PublicaçõesRESUMO
Aim and background: Combined endocyclophotocoagulation and phacoemulsification (ECP/Phaco) are uncommonly associated with complications. We present the first case of a rare complication following ECP/Phaco. Case description: A 72-year-old patient with dense nuclear sclerotic cataracts and primary open-angle glaucoma (POAG) underwent bilateral surgery uneventfully. He experienced a brief episode of postoperative elevated intraocular pressure (IOP), but only one eye with a lower baseline IOP developed a dilated pupil. No pupillary response was observed after applying 4% pilocarpine. The fixed mydriasis persisted without reaction to light or near stimulus, and the best-corrected vision (BCVA) was 20/30 in the affected eye. Conclusion: This case reports a possible rare complication when undergoing ECP/Phaco therapy. The pathogenesis of Urrets-Zavalia syndrome is unknown, but we hypothesized that eyes with more pronounced increases in IOP from baseline may be more susceptible to ischemic injury to the pupillary sphincter, resulting in a chronically dilated pupil. Clinical significance: Even a modest transient rise in postoperative IOP in a glaucomatous eye with normal baseline IOP could result in a chronically dilated pupil. How to cite this article: Cheng AMS, Vedula GG, Kubal AA, et al. Urrets-Zavalia Syndrome of Unresolving Mydriasis Following Endocyclophotocoagulation Combined with Phacoemulsification. J Curr Glaucoma Pract 2024;18(1):28-30.
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Objectives: We describe a case of anti-phospholipid syndrome (APLS) vasculopathy presenting with Moyamoya syndrome (MMS) and show the associated intracranial vessel wall MRI (VWI) findings. Methods: A 37-year-old-woman presented with acute onset dizziness and left-sided weakness. Neurologic exam revealed a left facial droop and left hemiparesis. She underwent a comprehensive laboratory work-up for stroke. Neuroimaging included a CT head, CT angiogram, VWI, and digital subtraction angiography. Results: Work-up revealed a triple-positive APLS antibody profile. CT of the head showed an acute right basal ganglia infarction and right frontal subarachnoid hemorrhage. CT angiogram revealed severe stenosis of the right internal carotid artery terminus in a Moyamoya pattern. Intracranial VWI showed long-segment concentric vessel wall thickening and homogeneous vessel wall enhancement and T2-hyperintense wall edema of the stenotic right ICA terminus, M1 middle cerebral artery, and A1 anterior cerebral artery. She was treated with long-term anticoagulation with warfarin and a right superficial temporal artery to middle cerebral artery bypass. Discussion: We present intracranial VWI features of vessel wall pathology in a patient with primary APLS presenting with MMS.
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Accurate measurement and interpretation of serum levels of troponin (Tn) is a central part of the clinical workup of a patient presenting with chest pain suspicious for acute coronary syndrome (ACS). Knowledge of the molecular characteristics of the troponin complex and test characteristics of troponin measurement assays allows for a deeper understanding of causes of false positive and false negative test results in myocardial injury. In this review, we discuss the molecular structure and functions of the constituent proteins of the troponin complex (TnT, TnC, and TnI); review the different isoforms of Tn and where they are from; survey the evolution of clinical Tn assays, ranging from first-generation to high-sensitivity (hs); provide a primer on statistical interpretation of assay results based on different clinical settings; and discuss potential causes of false results. We also summarize the advances in technologies that may lead to the development of future Tn assays, including the development of point of care assays and wearable Tn sensors for real-time continuous measurement.
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Engineering stabilized proteins is a fundamental challenge in the development of industrial and pharmaceutical biotechnologies. We present Stability Oracle: a structure-based graph-transformer framework that achieves SOTA performance on accurately identifying thermodynamically stabilizing mutations. Our framework introduces several innovations to overcome well-known challenges in data scarcity and bias, generalization, and computation time, such as: Thermodynamic Permutations for data augmentation, structural amino acid embeddings to model a mutation with a single structure, a protein structure-specific attention-bias mechanism that makes transformers a viable alternative to graph neural networks. We provide training/test splits that mitigate data leakage and ensure proper model evaluation. Furthermore, to examine our data engineering contributions, we fine-tune ESM2 representations (Prostata-IFML) and achieve SOTA for sequence-based models. Notably, Stability Oracle outperforms Prostata-IFML even though it was pretrained on 2000X less proteins and has 548X less parameters. Our framework establishes a path for fine-tuning structure-based transformers to virtually any phenotype, a necessary task for accelerating the development of protein-based biotechnologies.
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Mutação , Estabilidade Proteica , Proteínas , Termodinâmica , Proteínas/genética , Proteínas/química , Engenharia de Proteínas/métodos , Modelos Moleculares , Algoritmos , Redes Neurais de Computação , Conformação Proteica , Biologia Computacional/métodosRESUMO
Background: For patients undergoing long-construct fusion surgeries, simultaneous sacroiliac joint (SIJ) fusion is a growing trend in spine surgery. Some options for posterior SIJ fusion include 3D-printed triangular titanium implants or self-harvesting SIJ screws. Both implants require fixation within the sacrum and ileum. Fat embolism syndrome is a rare but known complication of lumbar pedicle instrumentation but has never been reported in association with SIJ fusion, regardless of implant type. We report the first two known cases of fat embolism associated with placement of SIJ fusion devices during long construct posterior spine fusion. Case Description: Case 1-a 50-year-old female with multiple previous spine surgeries complicated by osteomyelitis/diskitis that was successfully eradicated, underwent T10-pelvis posterior spinal fusion (PSF), L4 pedicle-subtracting-osteotomy, and bilateral SIJ fusion. During implantation of each SIJ fusion device, the patient's hemodynamic status deteriorated necessitating vasopressor support, intravenous fluid bolus, and hyperventilation, but quickly resolved. The case was completed without further issue, and she had an uneventful post-operative course. Case 2-a 71-year-old female with a past medical history of ankylosing spondylitis, previous L2-L5 PSF, rheumatoid arthritis on chronic steroids, underwent a T9-pelvis PSF, bilateral SIJ fusion, L4 pedicle subtraction osteotomy, T10-L1 Smith Peterson osteotomies. After implantation of the second SIJ fusion device, she became hypotensive and tachycardic, pulses were absent, and cardiopulmonary resuscitation was initiated. Pulses returned quickly, the index surgery was terminated, and she was transferred to the intensive care unit (ICU). In the ICU she was quickly weaned off the ventilator on post-operative day 1. On post-operative day 4, the patient returned to the operating room for completion of the surgery and had an extended, but uneventful, recovery afterwards. Conclusions: We report on the first two known cases of fat embolism syndrome occurring immediately after implantation of SIJ fusion devices. Spine surgeons should be aware of this rare, but potentially fatal, complication. Collaboration with the anesthesia team and optimization of the patient's hemodynamic status prior to implantation may help prevent catastrophic complications.
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INTRODUCTION: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics. METHODS: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure. RESULTS: Patients with completed management questionnaires (n = 142) had a median age of 64 (interquartile range: 59-69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (-52.0%) and detailed neuropsychological assessments (-63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and -50.0% in biomarker-positive and -negative cases, respectively). DISCUSSION: AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.
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INTRODUCTION: We described patients' and care partners' experiences with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing and result disclosure in routine care. METHODS: IMPACT-AD BC is an observational study of clinic patients who underwent AD CSF biomarker testing as part of their routine medical care (n = 142). In the personal utility arm of the study, semi-structured phone interviews were conducted with a subset of patients (n = 34), and separately with their care partners (n = 31). Post-disclosure interviews were conducted â¼1 month and â¼6 months after biomarker result disclosure and investigated the patients' decision-making process around testing, impact of receiving results, wellness and lifestyle changes, and future planning. RESULTS: A majority of patients (90%) rated their decision to undergo testing as "easy." Post-disclosure, the majority (82%) reported overall positive feelings from having greater certainty and the ability to plan ahead, and results spurred them to adopt/continue healthy behaviors such as exercise (84%) and cognitive activities (54%). Care partners expressed relief from having more diagnostic certainty, increased appreciation of future caregiving responsibilities, and a desire to connect with support resources. DISCUSSION: Perspectives of persons with lived experience in dementia provide new insight into the value of biomarker testing and should be included as part of evidence-guided considerations for pre-test counseling and result disclosure. Moreover, study findings identify an interval when patients and care partners are highly receptive to positive lifestyle and medical interventions.
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Electroporation (EP) stands out as a promising non-viral plasmid delivery strategy, although achieving optimal transfection efficiency in vivo remains a challenge. A noteworthy advancement in the field of in vivo EP is the application of hyaluronidase, an enzyme with the capacity to degrade hyaluronic acid in the extracellular matrix, which thereby enhances DNA transfer efficiency by 2- to 3-fold. This paper focuses on elucidating the mechanism of hyaluronidase's impact on transfection efficiency. We demonstrate that hyaluronidase promotes a more uniform distribution of plasmid DNA (pDNA) within skeletal muscle. Additionally, our study investigates the effect of the timing of hyaluronidase pretreatment on EP efficiency by including time intervals of 0, 5, and 30 min between hyaluronidase treatment and the application of pulses. Serum levels of the pDNA-encoded transgene reveal a minimal influence of the hyaluronidase pretreatment time on the final serum protein levels following delivery in both mice and rabbit models. Leveraging bioimpedance measurements, we capture morphological changes in muscle induced by hyaluronidase treatment, which result in a varied pDNA distribution. Subsequently, these findings are employed to optimize EP electrical parameters following hyaluronidase treatment in animal models. This paper offers novel insights into the potential of hyaluronidase in enhancing the effectiveness of in vivo EP, as well as guides optimized electroporation strategies following hyaluronidase use.
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Despite having high analytical sensitivities and specificities, qualitative SARS-CoV-2 nucleic acid amplification tests (NAATs) cannot distinguish infectious from non-infectious virus in clinical samples. In this study, we determined the highest cycle threshold (Ct) value of the SARS-CoV-2 targets in the Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4plex) test that corresponded to the presence of detectable infectious SARS-CoV-2 in anterior nasal swab samples. A total of 111 individuals with nasopharyngeal swab specimens that were initially tested by the Xpert Xpress SARS-CoV-2 test were enrolled. A healthcare worker subsequently collected anterior nasal swabs from all SARS-CoV-2-positive individuals, and those specimens were tested by the Xpert 4plex test, viral culture, and laboratory-developed assays for SARS-CoV-2 replication intermediates. SARS-CoV-2 Ct values from the Xpert 4plex test were correlated with data from culture and replication intermediate testing to determine the Xpert 4plex assay Ct value that corresponded to the presence of infectious virus. Ninety-eight of the 111 (88.3%) individuals initially tested positive by the Xpert Xpress SARS-CoV-2 test. An anterior nasal swab specimen collected from positive individuals a median of 2 days later (range, 0-9 days) tested positive for SARS-CoV-2 by the Xpert 4plex test in 39.8% (39/98) of cases. Of these samples, 13 (33.3%) were considered to contain infectious virus based on the presence of cultivable virus and replication intermediates, and the highest Ct value observed for the Xpert 4plex test in these instances was 26.3. Specimens that yielded Ct values of ≤26.3 when tested by the Xpert 4plex test had a likelihood of containing infectious SARS-CoV-2; however, no infectious virus was detected in specimens with higher Ct values.IMPORTANCEUnderstanding the correlation between real-time PCR test results and the presence of infectious SARS-CoV-2 may be useful for informing patient management and workforce return-to-work or -duty. Further studies in different patient populations are needed to correlate Ct values or other biomarkers of viral replication along with the presence of infectious virus in clinical samples.
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COVID-19 , Doenças Transmissíveis , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Nasofaringe , Técnicas de Diagnóstico Molecular/métodos , Teste para COVID-19RESUMO
BACKGROUND: Implicit bias poses a barrier to inclusivity in the health care workforce and is detrimental to patient care. While previous studies have investigated knowledge and training gaps related to implicit bias, emergency medicine (EM) leaders' self-awareness and perspectives on bias have not been studied. Using art to prompt reflections on implicit bias, this qualitative study explores (1) the attitudes of leaders in EM toward implicit bias and (2) individual or structural barriers to navigating and addressing bias in the workplace. METHODS: Investigators facilitated an hour-long workshop in May 2022 for those with leadership positions in the Society for Academic Emergency Medicine (SAEM), a leading national EM organization, including 62 attending physicians, eight residents/fellows, and four medical students. The workshop utilized arts-based methods to generate a psychologically supportive space to lead conversations around implicit bias in EM. The session included time for individual reflection, where participants used an electronic platform to respond anonymously to questions regarding susceptibility, fears, barriers, and experiences surrounding bias. Two independent coders compiled, coded, and reviewed the responses using an exploratory constructivist approach. RESULTS: A total of 125 responses were analyzed. Four major themes emerged: (1) acceptance that bias exists; (2) individual barriers, including fear of negative reactions, often due to power dynamics between respondents and other members of the ED; (3) institutional barriers, such as insufficient funding and unprotected time committed to addressing bias; and (4) ambiguity about defining and prioritizing bias. CONCLUSIONS: This qualitative analysis of reflections from an arts-based workshop highlights perceived fears and barriers that may impact EM physicians' motivation and comfort in addressing bias. These results may help guide interventions to address individual and structural barriers to mitigating bias in the workplace.