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Molecular Cancer May 2024Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear.
N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2.
BACKGROUND
Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear.
METHODS
We evaluated the expression pattern of SENP1 based on RNA sequencing data obtained from OHSU, TCGA, TARGET, and MILE datasets. Clinical samples were used to verify the expression of SENP1 in the AML cells. Lentiviral vectors shRNA and sgRNA were used to intervene in SENP1 expression in AML cells, and the effects of SENP1 on AML proliferation and anti-apoptosis were detected using in vitro and in vivo models. Chip-qPCR, MERIP-qPCR, CO-IP, RNA pulldown, and dual-luciferase reporter gene assays were used to explore the regulatory mechanisms of SNEP1 in AML.
RESULTS
SENP1 was significantly upregulated in high-risk AML patients and closely related to poor prognosis. The AKT/mTOR signaling pathway is a key downstream pathway that mediates SENP1's regulation of AML proliferation and anti-apoptosis. Mechanistically, the CO-IP assay revealed binding between SENP1 and HDAC2. SUMO and Chip-qPCR assays suggested that SENP1 can desumoylate HDAC2, which enhances EGFR transcription and activates the AKT pathway. In addition, we found that IGF2BP3 expression was upregulated in high-risk AML patients and was positively correlated with SENP1 expression. MERIP-qPCR and RIP-qPCR showed that IGF2BP3 binds SENP1 3-UTR in an m6A manner, enhances SENP1 expression, and promotes AKT pathway conduction.
CONCLUSIONS
Our findings reveal a distinct mechanism of SENP1-mediated HDAC2-AKT activation and establish the critical role of the IGF2BP3/SENP1signaling axis in AML development.
Topics: Animals; Female; Humans; Male; Mice; Adenosine; Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Cysteine Endopeptidases; Disease Progression; Gene Expression Regulation, Leukemic; Histone Deacetylase 2; Leukemia, Myeloid, Acute; Prognosis; Proto-Oncogene Proteins c-akt; RNA-Binding Proteins; Signal Transduction; Sumoylation; Xenograft Model Antitumor Assays
PubMed: 38822351
DOI: 10.1186/s12943-024-02013-y -
JAC-antimicrobial Resistance Jun 2024New dosing regimens for ceftriaxone 4 g/24 hours and ceftazidime 3 g/12 hours are convenient for patients receiving OPAT. To date, these have not been clinically...
BACKGROUND
New dosing regimens for ceftriaxone 4 g/24 hours and ceftazidime 3 g/12 hours are convenient for patients receiving OPAT. To date, these have not been clinically validated.
AIM
To assess the tolerability, toxicity and effectiveness of once daily ceftriaxone (4 g) and 12 hourly ceftazidime regimens (3 g twice a day) in the OPAT setting.
PATIENTS AND METHODS
From April 2018 until March 2023; demographic, clinical, microbiological and outcome data were collected on all adult patients discharged to a community-based OPAT team in East London.
RESULTS
There were 487 OPAT episodes. Fifty-three (10.9%) patients received ceftriaxone 4 g once a day and 20 (4.1%) ceftazidime 3 g twice a day. In the ceftriaxone group, the commonest conditions treated were orthopaedic, neurosurgical or diabetic foot infections. OPAT was used to expedite the discharge of 45 (84.9%) patients, the remainder were admission avoidance episodes. The commonest isolate causing infection was MSSA 23 (43.4%). There were no tolerability or toxicity episodes recorded. All patients were cured and bed days saved were 1266.In the smaller twice-daily ceftazidime cohort, seven (35%) patients were treated for necrotizing otitis externa, six (30%) for bronchiectasis and six (30%) for urinary tract infections. The commonest cause of infection was , 18 (90%). One case of nephrotoxicity was recorded. All patients were cured and bed days saved were 896.
CONCLUSIONS
Regimens of ceftriaxone 4 g once a day and ceftazidime 3 g twice a day were well tolerated and highly effective. If widely adopted, these regimens will save OPAT and nursing time and enable more patients to be treated.
PubMed: 38817948
DOI: 10.1093/jacamr/dlae079 -
Nicotine & Tobacco Research : Official... May 2024Factors that impact flavored tobacco sales restriction (flavor restrictions) effectiveness on youth e-cigarette behavior are unclear. Tobacco retailer density (retailer...
INTRODUCTION
Factors that impact flavored tobacco sales restriction (flavor restrictions) effectiveness on youth e-cigarette behavior are unclear. Tobacco retailer density (retailer density) is a health equity issue with greater retailer density in high-minority, low-income areas. We examined the association between flavor restrictions and youth e-cigarette behavior by retailer density across diverse communities in the California Bay Area.
AIMS AND METHODS
We analyzed data from the California Healthy Kids Survey using a difference-in-differences (DID) strategy. We compared pre- and post-policy changes in e-cigarette access and use one-year post-implementation among high school students in the Bay Area with a flavor restriction (n = 20 832) versus without (n = 66 126). Separate analyses were conducted for students in cities with low and high retailer density, with a median cutoff of 3.3 tobacco retailers/square mile.
RESULTS
Students with high retailer density were more likely to identify as a minority and have parents with lower education. Among students with low retailer density, flavor restrictions were associated with 24% lower odds in the pre- to post-policy increase in ease of access relative to unexposed students (DID = 0.76, 95% CI: 0.58, 0.99). Among students with high retailer density, flavor restrictions were associated with 26% higher odds in ease of access (DID: 1.26, 95% CI: 1.02, 1.56) and 57% higher odds of current use (DID = 1.57, 95% CI: 1.31, 1.87).
CONCLUSIONS
Flavor restrictions had positive impacts on youth e-cigarette access in low, but not high retailer density cities. From a health equity perspective, our results underscore how flavor restrictions may have uneven effects among vulnerable groups.
IMPLICATIONS
In diverse communities in the California Bay Area, our results suggest a protective association between flavored tobacco sales restrictions and youth access to e-cigarettes in low, but not high tobacco retailer density cities one-year post-implementation. These results underscore how flavor restrictions may have uneven effects, and when implemented in high retailer density areas, may disproportionately place already vulnerable groups at heightened exposure to e-cigarette use and access. In high retailer density areas, additional tobacco control efforts may need to be included with flavor restriction implementation, such as increased education, youth prevention and cessation programs, policies to reduce tobacco retailer density, or stronger tobacco retailer enforcement or compliance monitoring.
Topics: Humans; California; Electronic Nicotine Delivery Systems; Adolescent; Flavoring Agents; Commerce; Female; Male; Tobacco Products; Vaping; Students
PubMed: 38817027
DOI: 10.1093/ntr/ntad129 -
BMC Nursing May 2024Unit nurse managers hold essential positions that can facilitate implementation of evidence-based practice. Studies showed that nurse managers in China lacked...
Development of a training program prototype to enhance implementation leadership competencies and behaviours of Chinese unit nurse managers: a qualitative descriptive study.
BACKGROUND
Unit nurse managers hold essential positions that can facilitate implementation of evidence-based practice. Studies showed that nurse managers in China lacked competencies and behaviours necessary to lead evidence-based practice implementation. The aim of the current study was to develop a context-fit training program prototype to enhance leadership competencies and behaviours regarding evidence-based practice implementation of Chinese unit nurse managers.
METHOD
We used a descriptive qualitative study design and followed the integrated knowledge translation approach to co-develop the prototype in a tertiary hospital in Changsha, China. Seven nurse managers from the participated hospital and a researcher co-developed the prototype based on the Ottawa Model of Implementation Leadership (O-MILe). The development process encompassed four phases from November 2021 to March 2022 that involved group discussions (n = 4) and individual interviews (n = 21). All data were analysed by two independent researchers using the thematic analysis method.
RESULTS
Managers agreed that all O-MILe behaviours were important to evidence-based practice implementation, and only minor modifications were needed for clarification and adaptation. The actions managers identified that could operationalize the leadership behaviours were related to current clinical practices, evidence-based practice, nurses, patients, interprofessional staff members, incentives and resources, organization and external entities. Three types of general competencies related to evidence-based practice, professional nursing, and implementation leadership were identified. Multimodal activities such as lectures, experience sharing, group discussions, plan development and coaching were suggested to deliver the training program.
CONCLUSIONS
All O-MILe leadership behaviours were perceived as essential for unit nurse managers to lead EBP implementation in the hospital context in China. We identified the leadership actions and the competencies required for nursing managers to implement EBP in China. Further studies are required to evaluate the acceptability and impact of this prototype. Further studies with large sample sizes across various clinical settings are needed to facilitate the generalization of the findings and gain an in-depth understanding of the program.
PubMed: 38816867
DOI: 10.1186/s12912-024-01989-8 -
Heliyon May 2024Tracing individual cell pathways among the whole population is crucial for understanding their behavior, cell communication, migration dynamics, and fate. Optical...
Tracing individual cell pathways among the whole population is crucial for understanding their behavior, cell communication, migration dynamics, and fate. Optical labeling is one approach for tracing individual cells, but it typically requires genetic modification to induce the generation of photoconvertible proteins. Nevertheless, this approach has limitations and is not applicable to certain cell types. For instance, genetic modification often leads to the death of macrophages. This study aims to develop an alternative method for labeling macrophages by utilizing photoconvertible micron-sized capsules capable of easy internalization and prolonged retention within cells. Thermal treatment in a polyvinyl alcohol gel medium is employed for the scalable synthesis of capsules with a wide range of fluorescent dyes, including rhodamine 6G, pyronin B, fluorescein, acridine yellow, acridine orange, thiazine red, and previously reported rhodamine B. The fluorescence brightness, photostability, and photoconversion ability of the capsules are evaluated using confocal laser scanning microscopy. Viability, uptake, mobility, and photoconversion studies are conducted on RAW 264.7 and bone marrow-derived macrophages, serving as model cell lines. The production yield of the capsules is increased due to the use of polyvinyl alcohol gel, eliminating the need for conventional filtration steps. Capsules entrapping rhodamine B and rhodamine 6G meet all requirements for intracellular use in individual cell tracking. Mass spectrometry analysis reveals a sequence of deethylation steps that result in blue shifts in the dye spectra upon irradiation. Cellular studies on macrophages demonstrate robust uptake of the capsules. The capsules exhibit minimal cytotoxicity and have a negligible impact on cell motility. The successful photoconversion of RhB-containing capsules within cells highlights their potential as alternatives to photoconvertible proteins for individual cell labeling, with promising applications in personalized medicine.
PubMed: 38813172
DOI: 10.1016/j.heliyon.2024.e30680 -
PloS One 2024In response to biodiversity loss and biotic community homogenization in urbanized landscapes, there are increasing efforts to conserve and increase biodiversity within...
In response to biodiversity loss and biotic community homogenization in urbanized landscapes, there are increasing efforts to conserve and increase biodiversity within urban areas. Accordingly, around the world, previously extirpated species are (re)colonizing and otherwise infiltrating urban landscapes, while other species are disappearing from these landscapes. Tracking the occurrence of traditionally urban intolerant species and loss of traditionally urban tolerant species should be a management goal of urban areas, but we generally lack tools to study this phenomenon. To address this gap, we first used species' occurrences from iNaturalist, a large collaborative dataset of species observations, to calculate an urban association index (UAI) for 967 native animal species that occur in the city of Los Angeles. On average, the occurrence of native species was negatively associated with our composite measure of urban intensity, with the exception of snails and slugs, which instead occur more frequently in areas of increased urban intensity. Next, we assessed 8,348 0.25 x 0.25 mile grids across the City of Los Angeles to determine the average grid-level UAI scores (i.e., a summary of the UAIs present in a grid cell, which we term Community Urban Tolerance Index or CUTI). We found that areas of higher urban intensity host more urban tolerant species, but also that taxonomic groups differ in their aggregate tolerance of urban areas, and that spatial patterns of tolerance vary between groups. The framework established here has been designed to be iteratively reevaluated by city managers of Los Angeles in order to track the progress of initiatives to preserve and encourage urban biodiversity, but can be rescaled to sample different regions within the city or different cities altogether to provide a valuable tool for city managers globally.
Topics: Animals; Biodiversity; Cities; California; Los Angeles; Conservation of Natural Resources; Urbanization; Ecosystem
PubMed: 38809860
DOI: 10.1371/journal.pone.0295476 -
Heliyon May 2024Giant cell tumor of bone is a commonly encountered aggressive epiphyseal bone tumor, most often treated surgically. The natural history and presentation are classically... (Review)
Review
Giant cell tumor of bone is a commonly encountered aggressive epiphyseal bone tumor, most often treated surgically. The natural history and presentation are classically described but the histopathology is poorly understood. Intralesional curettage is the mainstay of treatment, but there is significant variation in the use of adjuvant and cavity filling modalities. No gold standard has been agreed upon for treatment, and a variety of techniques are currently in use. Given its location, secondary osteoarthritis is a known long-term complication. This review examines the natural history of giant cell tumors, treatment options and complications, and subsequent development of osteoarthritis. Arthroplasty is usually indicated for secondary osteoarthritis although data is limited on its efficacy. Further directions will likely center on improved pharmacological treatments as well as improved arthroplasty techniques.
PubMed: 38807896
DOI: 10.1016/j.heliyon.2024.e30890 -
Journal of Orthopaedic Surgery and... May 2024A combined injury of the patellar tendon and both the anterior and posterior cruciate ligaments is disabling. It directly affects knee kinematics and biomechanics,... (Review)
Review
A combined injury of the patellar tendon and both the anterior and posterior cruciate ligaments is disabling. It directly affects knee kinematics and biomechanics, presenting a considerable surgical challenge. In this complex and uncommon injury, decision-making should take into account the surgeon's experience and consider one- or two-stage surgery, tendon graft, graft fixation, and rehabilitation protocol. This manuscript discusses the surgical approach based on a comprehensive understanding of the patellar tendon and bicruciate biomechanics to guide which structures should be reconstructed first, especially when a two-stage procedure is chosen.
Topics: Humans; Patellar Ligament; Anterior Cruciate Ligament Injuries; Biomechanical Phenomena; Knee Injuries; Posterior Cruciate Ligament; Chronic Disease
PubMed: 38807155
DOI: 10.1186/s13018-024-04724-w -
Spine Deformity May 2024Patients who undergo growth-friendly (GF) treatment for early-onset scoliosis (EOS) undergo multiple clinical and surgical encounters. We sought to quantify the...
PURPOSE
Patients who undergo growth-friendly (GF) treatment for early-onset scoliosis (EOS) undergo multiple clinical and surgical encounters. We sought to quantify the associated temporal and travel burden and estimate subsequent cost.
METHODS
Four centers in an international study group combined data on EOS patients who underwent surgical GF treatment from 2006 to 2021. Data collected included demographics, scoliosis etiology, GF implant, encounter type, and driving distance. We applied 2022 IRS and BLS data or $0.625/mile and $208.2/day off work to calculate a relative financial burden.
RESULTS
A total of 300 patients were analyzed (55% female). Etiologies were: congenital (33.3%), idiopathic (18.7%), neuromuscular (30.7%), and syndromic (17.3%). The average age at the index procedure was 5.5 years. For the 300 patients, 5899 encounters were recorded (average 18 encounters/patient). Aggregate encounter types were 2521 clinical office encounters (43%), 2045 surgical lengthening encounters (35%), 1157 magnetic lengthening encounters (20%), 149 spinal fusions (3%), and 27 spinal fusion revisions (0.5%). When comparing patients by scoliosis etiology or by GF implant type, no significant differences were noted in the total number of encounters or average travel distance. Patients traveled a median round trip distance of 158 miles/encounter between their homes and treating institutions (range 2.4-5654 miles), with a cumulative median distance of 2651 miles for the entirety of their treatment (range 29-90,552 miles), at an estimated median cost of $1656.63. The mean number of days off work was 18 (range 3-75), with an associated loss of $3643.50 in income.
CONCLUSION
Patients with EOS averaged 18 encounters for GF surgical treatment. These patients and their families traveled a median distance of 158 miles/encounter, with an estimated combined mileage and loss of income of $5300.
PubMed: 38796814
DOI: 10.1007/s43390-024-00895-y -
Archives of Psychiatric Nursing Jun 2024Mobile mental health applications are a novel treatment method with unique qualities and capabilities for enhancing existing psychiatric treatments. Outpatient settings...
INTRODUCTION
Mobile mental health applications are a novel treatment method with unique qualities and capabilities for enhancing existing psychiatric treatments. Outpatient settings such as Mile Square Health Clinic have identified a need to leverage this new technology into their routine care.
BACKGROUND
In the U.S., over 40 million people suffer from an anxiety disorder, however, only 1 in 4 responds to pharmacological treatment. Preliminary research indicates mental health apps are acceptable, feasible, and can improve patient outcomes for those with anxiety.
METHODS
Participants from two different outpatient psychiatric clinics locations with generalized anxiety disorder were identified and recruited by participating nurse practitioners. Participants were instructed on how to download and use IntelliCare by the Project Lead. The Project Lead administered a semi-structured interview to collect qualitative data at three weeks and six weeks follow-up.
RESULTS AND CONCLUSIONS
Survey responses at three and six weeks showed relevant themes of increased journaling, increased feelings of connectedness, positive associations with gamification, and IntelliCare being most useful for a moderate to severe level of anxiety.
RECOMMENDATIONS
The results of this QI project demonstrate the clinical utility of incorporating the IntelliCare app into regular outpatient practice. IntelliCare should be used with those with moderate to severe anxiety and journaling features should follow research developments to incorporate best-practice guidelines.
Topics: Humans; Quality Improvement; Mobile Applications; Female; Male; Anxiety Disorders; Adult; Telemedicine; Outpatients; Surveys and Questionnaires; Middle Aged
PubMed: 38789238
DOI: 10.1016/j.apnu.2024.03.017