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1.
Ann Surg ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38989569

ABSTRACT

OBJECTIVE: The purpose of this study was to determine quality improvement outcomes following the pilot implementation of an in-situ simulation designed to enhance surgical safety checklist performance. BACKGROUND: OR Black Box (ORBB) technology allows near real-time assessment for surgical safety checklist performance. Before our study, timeout quality was 73.3%, compliance was 99.9%, and engagement was 89.7% (n=1993 cases); Debrief Quality was 76.0%, compliance was 66.9%, and engagement was 66.7% (n=1842 cases). METHODS: This IRB-approved study used prospective convergent multi-methods. During 2 months, a 15-minute in-situ simulation, incorporating rapid cycle deliberate practice, was implemented for OR teams. ORBB analytics generated Timeout and Debrief scores for actual operations performed by surgeons who participated in simulation (Sim-group) versus those who did not (No-sim group) over 6 months, including 2 months pre-intervention, during-intervention, and post-intervention. Inductive content analysis was performed based on simulation discussions to determine team member perspectives. RESULTS: Thirty simulations with 163 interprofessional participants were conducted. ORBB data from 1570 cases were analyzed. Scores were significantly better for the Sim-group compared with the No-sim group for debrief quality (84% vs. 79% P<0.001, during-intervention), compliance (73% vs. 66%, P<0.001, post-intervention), and engagement (80% vs. 73%, P=0.012, during-intervention). There were no between-group differences for Timeout scores. Thematic analysis identified 2 primary categories: "culture of safety" and "policy." CONCLUSIONS: This simulation-based QI intervention created a psychologically safe training environment for OR teams. The novel use of ORBB technology facilitated outcome analysis and showed significantly better Debrief scores for simulation-trained surgeons compared with nontrained surgeons.

2.
J Environ Manage ; 365: 121673, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38959765

ABSTRACT

We used UAV-LiDAR technology and other advanced remote sensing techniques to evaluate mangrove rehabilitation projects along the eroding shoreline of the Upper Gulf of Thailand. Our results delineate the necessary biophysical conditions for successfully rehabilitating mangroves, establishing optimal conditions under which mangroves can naturally re-establish and thrive. Furthermore, we investigated the effectiveness of different coastal defense structures in fostering mangrove recolonization. Our analysis shows that nearshore breakwaters markedly outperform submerged breakwaters and bamboo fences, with a success rate of over 65% by significantly reducing wave energy that aids sediment trapping. These findings suggest that refinements in the configuration of coastal structures, including the elevation of breakwater crests and selective deployment of bamboo fences, will enhance mangrove rehabilitation success. These insights affirm the role of UAV-LiDAR surveys for optimizing mangrove restoration initiatives, thereby facilitating sustainable development for coastlines plagued by erosion. The insights gleaned offer a blueprint for bolstering the success rate of mangrove rehabilitation projects, directing them toward sustainable coastal development.

3.
BMJ Case Rep ; 17(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960430

ABSTRACT

Malignant phyllodes tumours (PTs) are aggressive neoplasms with high rates of local recurrence and distant metastasis. With no known effective chemotherapy and no approved targeted therapy in the setting of metastatic disease, prognosis is limited with an often-relapsing course of disease. We report a case of a woman in her late 30s with a diagnosis of recurrent metastatic malignant PT who was found to have acrometastases of the malignant PT to the right distal index and small digits. We emphasise the potential for atypical patterns of metastases in patients with malignant PT and the need to recognise acrometastasis as an unusual but morbid manifestation of disease. Given the high growth rate of malignant PTs, the lack of systemic treatment options, and the ensuing distress for patients, prompt diagnosis and early intervention is crucial.


Subject(s)
Bone Neoplasms , Breast Neoplasms , Neoplasm Recurrence, Local , Phyllodes Tumor , Humans , Phyllodes Tumor/pathology , Phyllodes Tumor/secondary , Phyllodes Tumor/diagnosis , Female , Breast Neoplasms/pathology , Adult , Bone Neoplasms/secondary
4.
Front Med (Lausanne) ; 11: 1343646, 2024.
Article in English | MEDLINE | ID: mdl-38952865

ABSTRACT

Objectives: The majority of patients with respiratory illness are seen in primary care settings. Given COVID-19 is predominantly a respiratory illness, the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), assessed the pandemic impact on primary care visits for respiratory illnesses. Design: Definitions for respiratory illness types were agreed on collectively. Monthly visit counts with diagnosis were shared centrally for analysis. Setting: Primary care settings in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden and the United States. Participants: Over 38 million patients seen in primary care settings in INTRePID countries before and during the pandemic, from January 1st, 2018, to December 31st, 2021. Main outcome measures: Relative change in the monthly mean number of visits before and after the onset of the pandemic for acute infectious respiratory disease visits including influenza, upper and lower respiratory tract infections and chronic respiratory disease visits including asthma, chronic obstructive pulmonary disease, respiratory allergies, and other respiratory diseases. Results: INTRePID countries reported a marked decrease in the average monthly visits for respiratory illness. Changes in visits varied from -10.9% [95% confidence interval (CI): -33.1 to +11.3%] in Norway to -79.9% (95% CI: -86.4% to -73.4%) in China for acute infectious respiratory disease visits and - 2.1% (95% CI: -12.1 to +7.8%) in Peru to -59.9% (95% CI: -68.6% to -51.3%) in China for chronic respiratory illness visits. While seasonal variation in allergic respiratory illness continued during the pandemic, there was essentially no spike in influenza illness during the first 2 years of the pandemic. Conclusion: The COVID-19 pandemic had a major impact on primary care visits for respiratory presentations. Primary care continued to provide services for respiratory illness, although there was a decrease in infectious illness during the COVID pandemic. Understanding the role of primary care may provide valuable information for COVID-19 recovery efforts and planning for future global emergencies.

5.
J Med Chem ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953866

ABSTRACT

Zoonotic coronaviruses are known to produce severe infections in humans and have been the cause of significant morbidity and mortality worldwide. SARS-CoV-2 was the largest and latest contributor of fatal cases, even though MERS-CoV has the highest case-fatality ratio among zoonotic coronaviruses. These infections pose a high risk to public health worldwide warranting efforts for the expeditious discovery of antivirals. Hence, we hereby describe a novel series of inhibitors of coronavirus 3CLpro embodying an N-substituted 2-pyrrolidone scaffold envisaged to exploit favorable interactions with the S3-S4 subsites and connected to an invariant Leu-Gln P2-P1 recognition element. Several inhibitors showed nanomolar antiviral activity in enzyme and cell-based assays, with no significant cytotoxicity. High-resolution crystal structures of inhibitors bound to the 3CLpro were determined to probe and identify the molecular determinants associated with binding, to inform the structure-guided optimization of the inhibitors, and to confirm the mechanism of action of the inhibitors.

6.
J Phys Ther Educ ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38954765

ABSTRACT

INTRODUCTION: The 2 aims of this observational study are (a) to describe the implementation and feasibility of a bed mobility skills simulation-based mastery learning (SBML) curricular module for physical therapist students and (b) to measure learning outcomes and student perceptions of this module. REVIEW OF LITERATURE: Simulation-based mastery learning is an outcome-based educational approach that has been successful in other health professions but has not been explored in physical therapy education. SUBJECTS: Eighty-seven students in a single cohort of a Doctor of Physical Therapy program. METHODS: The SBML module in this pretest-posttest study included a pretest, instruction, initial posttest, and additional rounds of instruction and assessment as needed for all learners to achieve the minimum passing standard (MPS) set using the Mastery Angoff and Patient Safety methods. Outcome measures were bed mobility assessment pass rates and scores, additional student and faculty time compared with a traditional approach, and student perceptions of their self-confidence and the module. RESULTS: All students achieved the MPS after 3 rounds of training and assessment beyond the initial posttest. Mean Total Scores improved from 67.6% (12.9%) at pretest to 91.4% (4.8%) at mastery posttest (P < .001, Cohen's d = 1.8, 95% CI [1.4-2.1]); mean Safety Scores improved from 75.2% (16.0%) at pretest to 100.0% (0.0%) at mastery posttest (P < .001, Cohen's d = 1.5, 95% CI [1.2-1.9]). Students who did not achieve the MPS at the initial posttest (n = 30) required a mean of 1.2 hours for additional instruction and assessment. Survey results revealed an increase in student confidence (P < .001) and positive student perceptions of the module. DISCUSSION AND CONCLUSION: Implementation of this SBML module was feasible and resulted in uniformly high levels of bed mobility skill acquisition. Based on rigorous learning outcomes, feasible requirements for implementation, and increased student confidence, SBML offers a promising approach for wider implementation in physical therapy education.

7.
bioRxiv ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38948761

ABSTRACT

The ecological and evolutionary success of multicellular lineages is due in no small part to their increased size relative to unicellular ancestors. However, large size also poses biophysical challenges, especially regarding the transport of nutrients to all cells; these constraints are typically overcome through multicellular innovations (e.g., a circulatory system). Here we show that an emergent biophysical mechanism - spontaneous fluid flows arising from metabolically-generated density gradients - can alleviate constraints on nutrient transport, enabling exponential growth in nascent multicellular clusters of yeast lacking any multicellular adaptations for nutrient transport or fluid flow. Surprisingly, beyond a threshold size, the metabolic activity of experimentally-evolved snowflake yeast clusters drives large-scale fluid flows that transport nutrients throughout the cluster at speeds comparable to those generated by the cilia of extant multicellular organisms. These flows support exponential growth at macroscopic sizes that theory predicts should be diffusion limited. This work demonstrates how simple physical mechanisms can act as a 'biophysical scaffold' to support the evolution of multicellularity by opening up phenotypic possibilities prior to genetically-encoded innovations. More broadly, our findings highlight how co-option of conserved physical processes is a crucial but underappreciated facet of evolutionary innovation across scales.

10.
Front Immunol ; 15: 1408710, 2024.
Article in English | MEDLINE | ID: mdl-38947320

ABSTRACT

Background: Interleukin-17 (IL-17) family cytokines promote protective inflammation for pathogen resistance, but also facilitate autoimmunity and tumor development. A direct signal of IL-17 to regulatory T cells (Tregs) has not been reported and may help explain these dichotomous responses. Methods: We generated a conditional knockout of Il17ra in Tregs by crossing Foxp3-YFP-Cre mice to Il17ra-flox mice (Il17ra ΔTreg mice). Subsequently, we adoptively transferred bone marrow cells from Il17ra ΔTreg mice to a mouse model of sporadic colorectal cancer (Cdx2-Cre +/Apc F/+), to selectively ablate IL-17 direct signaling on Tregs in colorectal cancer. Single cell RNA sequencing and bulk RNA sequencing were performed on purified Tregs from mouse colorectal tumors, and compared to those of human tumor infiltrating Treg cells. Results: IL-17 Receptor A (IL-17RA) is expressed in Tregs that reside in mouse mesenteric lymph nodes and colon tumors. Ablation of IL-17RA, specifically in Tregs, resulted in increased Th17 cells, and exacerbated tumor development. Mechanistically, tumor-infiltrating Tregs exhibit a unique gene signature that is linked to their activation, maturation, and suppression function, and this signature is in part supported by the direct signaling of IL-17 to Tregs. To study pathways of Treg programming, we found that loss of IL-17RA in tumor Tregs resulted in reduced RNA splicing, and downregulation of several RNA binding proteins that are known to regulate alternative splicing and promote Treg function. Conclusion: IL-17 directly signals to Tregs and promotes their maturation and function. This signaling pathway constitutes a negative feedback loop that controls cancer-promoting inflammation in CRC.


Subject(s)
Interleukin-17 , Mice, Knockout , T-Lymphocytes, Regulatory , Animals , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Interleukin-17/metabolism , Mice , Humans , Receptors, Interleukin-17/genetics , Receptors, Interleukin-17/metabolism , Colorectal Neoplasms/immunology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Mice, Inbred C57BL , Signal Transduction , Disease Models, Animal
11.
Pract Radiat Oncol ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38972541

ABSTRACT

PURPOSE: Patients undergoing radiation therapy may terminate treatment for any number of reasons. The incidence of treatment termination (TT) during radiation therapy has not been studied. Herein we present a cohort of TT at a large multi-center radiation oncology department over 10 years. METHODS AND MATERIALS: TTs between 1/2013 and 1/2023 were prospectively analyzed as part of an ongoing departmental quality and safety program. TT was defined as any premature discontinuation of therapy after initiating radiation planning. The rate of TT was calculated as a percentage of all patients starting radiation planning. All cases were presented at monthly morbidity and mortality (MM) conferences with a root cause reviewed (RCA). RESULTS: A total of 1,448 TTs were identified out of 31,199 planned courses of care (4.6%). Six hundred eighty-six (47.4%) involved patients treated with curative intent, while 753 (52.0%) with palliative intent, and 9 (0.6%) for benign disease. The rate of TT decreased from 8.49% in 2013 to 3.02% in 2022 with rates decreasing yearly. The most common disease sites for TT were CNS (21.7%), H&N (19.3%), Thorax (17.5%), and Bone (14.2%). The most common causes of TT were hospice and/or patient expiration (35.9%), patient choice unrelated to toxicity (35.2%), and clinician choice unrelated to toxicity (11.5%). CONCLUSION: This 10-year prospective review of TTs identified a year-over-year decrease in TTs as a percentage of planned patients. This decrease may be associated with the addition of RCA for TTs and discussion monthly at MM rounds, coupled with departmental upstream quality initiatives implemented over time. Understanding the reasons behind TTs may help to decrease preventable TTs. While some TTs may be unavoidable, open discourse and quality improvement changes effectively reduce TT incidents over time.

12.
Expert Opin Investig Drugs ; : 1-9, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973395

ABSTRACT

INTRODUCTION: LX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future. AREAS COVERED: This paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed. EXPERT OPINION: In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.

13.
Article in English | MEDLINE | ID: mdl-38981068

ABSTRACT

Glass ceramic (GC) is the most promising material for objective lenses for extreme ultraviolet lithography that must meet the subnanometer precision, which is characterized by low values of high spatial frequency surface roughness (HSFR). However, the HSFR of GC is typically degraded during ion beam figuring (IBF). Herein, a developed method for constructing molecular dynamics (MD) models of GC was presented, and the formation mechanisms of surface morphologies were investigated. The results indicated that the generation of the dot-like microstructure was the result of the difference in the erosion rate caused by the difference in the intrinsic properties between ceramic phases (CPs) and glass phases (GPs). Further, the difference in the microstructure of the IBF surface under different beam angles was mainly caused by the difference in the two types of sputtering. Quantum mechanical calculations showed that the presence of interstitial atoms would result in electron rearrangement and that the electron localization can lead to a reduction in CP stability. To obtain a homogeneous surface, the effects of beam parameters on the heterogeneous surface were systematically investigated based on the proposed MD model. Then, a novel ion beam modification (IBM) method was proposed and demonstrated by TEM and GIXRD. The range of ion beam smoothing parameters that could effectively converge the HSFR of the modified surface was determined through numerous experiments. Using the optimized beam parameters, an ultrathin homogeneous modified surface within 3 nm was obtained. The HSFR of GC smoothed by ion beam modification-assisted smoothing (IBMS) dropped from 0.348 to 0.090 nm, a 74% reduction. These research results offer a deeper understanding of the morphology formation mechanisms of the GC surfaces involved in ion beam processing and may point to a new approach for achieving ultrasmooth heterostructure surfaces down to the subnanometer scale.

14.
JAMA Netw Open ; 7(7): e2420218, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38985474

ABSTRACT

Importance: Handheld phone use while driving is a major factor in vehicle crashes. Scalable interventions are needed to encourage drivers not to use their phones. Objective: To test whether interventions involving social comparison feedback and/or financial incentives can reduce drivers' handheld phone use. Design, Setting, and Participants: In a randomized clinical trial, interventions were administered nationwide in the US via a mobile application in the context of a usage-based insurance program (Snapshot Mobile application). Customers were eligible to be invited to participate in the study if enrolled in the usage-based insurance program for 30 to 70 days. The study was conducted from May 13 to June 30, 2019. Analysis was completed December 22, 2023. Interventions: Participants were randomly assigned to 1 of 6 trial arms for a 7-week intervention period: (1) control; (2) feedback, with weekly push notification about their handheld phone use compared with that of similar others; (3) standard incentive, with a maximum $50 award at the end of the intervention based on how their handheld phone use compared with similar others; (4) standard incentive plus feedback, combining interventions of arms 2 and 3; (5) reframed incentive plus feedback, with a maximum $7.15 award each week, framed as participant's to lose; and (6) doubled reframed incentive plus feedback, a maximum $14.29 weekly loss-framed award. Main Outcome and Measure: Proportion of drive time engaged in handheld phone use in seconds per hour (s/h) of driving. Analyses were conducted with the intention-to-treat approach. Results: Of 17 663 customers invited by email to participate, 2109 opted in and were randomized. A total of 2020 drivers finished the intervention period (68.0% female; median age, 30 [IQR, 25-39] years). Median baseline handheld phone use was 216 (IQR, 72-480) s/h. Relative to control, feedback and standard incentive participants did not reduce their handheld phone use. Standard incentive plus feedback participants reduced their use by -38 (95% CI, -69 to -8) s/h (P = .045); reframed incentive plus feedback participants reduced their use by -56 (95% CI, -87 to -26) s/h (P < .001); and doubled reframed incentive plus feedback participants reduced their use by -42 s/h (95% CI, -72 to -13 s/h; P = .007). The 5 active treatment arms did not differ significantly from each other. Conclusions and Relevance: In this randomized clinical trial, providing social comparison feedback plus incentives reduced handheld phone use while individuals were driving. Trial Registration: ClinicalTrials.gov Identifier: NCT03833219.


Subject(s)
Automobile Driving , Motivation , Humans , Female , Male , Adult , Automobile Driving/psychology , Automobile Driving/statistics & numerical data , Middle Aged , Cell Phone Use/statistics & numerical data , Mobile Applications , Feedback , United States
15.
Nat Struct Mol Biol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951624

ABSTRACT

During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAPs), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, here we use time-resolved cryogenic electron microscopy (cryo-EM) to capture four intermediates populated 120 ms or 500 ms after mixing Escherichia coli σ70-RNAP and the λPR promoter. Cryo-EM snapshots revealed that the upstream edge of the transcription bubble unpairs rapidly, followed by stepwise insertion of two conserved nontemplate strand (nt-strand) bases into RNAP pockets. As the nt-strand 'read-out' extends, the RNAP clamp closes, expelling an inhibitory σ70 domain from the active-site cleft. The template strand is fully unpaired by 120 ms but remains dynamic, indicating that yet unknown conformational changes complete RPo formation in subsequent steps. Given that these events likely describe DNA opening at many bacterial promoters, this study provides insights into how DNA sequence regulates steps of RPo formation.

16.
Health Serv Res ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956400

ABSTRACT

OBJECTIVE: To determine the budget impact of implementing multidisciplinary complex pain clinics (MCPCs) for Veterans Health Administration (VA) patients living with complex chronic pain and substance use disorder comorbidities who are on risky opioid regimens. DATA SOURCES AND STUDY SETTING: We measured implementation costs for three MCPCs over 2 years using micro-costing methods. Intervention and downstream costs were obtained from the VA Managerial Cost Accounting System from 2 years prior to 2 years after opening of MCPCs. STUDY DESIGN: Staff at the three VA sites implementing MCPCs were supported by Implementation Facilitation. The intervention cohort was patients at MCPC sites who received treatment based on their history of chronic pain and risky opioid use. Intervention costs and downstream costs were estimated with a quasi-experimental study design using a propensity score-weighted difference-in-difference approach. The healthcare utilization costs of treated patients were compared with a control group having clinically similar characteristics and undergoing the standard route of care at neighboring VA medical centers. Cancer and hospice patients were excluded. DATA COLLECTION/EXTRACTION METHODS: Activity-based costing data acquired from MCPC sites were used to estimate implementation costs. Intervention and downstream costs were extracted from VA administrative data. PRINCIPAL FINDINGS: Average Implementation Facilitation costs ranged from $380 to $640 per month for each site. Upon opening of three MCPCs, average intervention costs per patient were significantly higher than the control group at two intervention sites. Downstream costs were significantly higher at only one of three intervention sites. Site-level differences were due to variation in inpatient costs, with some confounding likely due to the COVID-19 pandemic. This evidence suggests that necessary start-up investments are required to initiate MCPCs, with allocations of funds needed for implementation, intervention, and downstream costs. CONCLUSIONS: Incorporating implementation, intervention, and downstream costs in this evaluation provides a thorough budget impact analysis, which decision-makers may use when considering whether to expand effective programming.

17.
Nature ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987585

ABSTRACT

In lactating mothers, the high calcium (Ca2+) demand for milk production triggers significant bone loss1. Although oestrogen normally counteracts excessive bone resorption by promoting bone formation, this sex steroid drops precipitously during this postpartum period. Here we report that brain-derived cellular communication network factor 3 (CCN3) secreted from KISS1 neurons of the arcuate nucleus (ARCKISS1) fills this void and functions as a potent osteoanabolic factor to build bone in lactating females. We began by showing that our previously reported female-specific, dense bone phenotype2 originates from a humoral factor that promotes bone mass and acts on skeletal stem cells to increase their frequency and osteochondrogenic potential. This circulatory factor was then identified as CCN3, a brain-derived hormone from ARCKISS1 neurons that is able to stimulate mouse and human skeletal stem cell activity, increase bone remodelling and accelerate fracture repair in young and old mice of both sexes. The role of CCN3 in normal female physiology was revealed after detecting a burst of CCN3 expression in ARCKISS1 neurons coincident with lactation. After reducing CCN3 in ARCKISS1 neurons, lactating mothers lost bone and failed to sustain their progeny when challenged with a low-calcium diet. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone for both sexes and define a new maternal brain hormone for ensuring species survival in mammals.

18.
Nature ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987596

ABSTRACT

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection5. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.

19.
Chin J Cancer Res ; 36(3): 341-350, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38988484

ABSTRACT

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

20.
Front Public Health ; 12: 1413258, 2024.
Article in English | MEDLINE | ID: mdl-38989114

ABSTRACT

As a result of the United States withdrawal from Afghanistan in fall 2021, 1,260 Afghan evacuees arrived in Minnesota between October 2021 and February 2022. Several contextual factors including an overtaxed health system under duress from COVID-19 and uncertain benefit eligibility prompted a coordinated public health response to appropriately address the acute and pressing medical concerns of our new neighbors. This community case study describes the State of Minnesota's cross-sectoral response that created a welcoming environment, identified public health concerns, and addressed acute medical needs. Medical volunteers provided an initial health and safety check for Afghan families upon arrival. Volunteers also offered onsite culturally and linguistically appropriate mental health assessments, group therapy, women's clinics, vaccine clinics, medication refills, and ongoing walk-in primary care. Care coordinators facilitated primary care and specialty care referrals. The majority (96%) of eligible arrivals were screened as part of this response and the median time between arrival to Minnesota and initial health screening was 2 days. Half of all arrivals screened reported at least one health concern and 56% were referred to a specialty for further evaluation. Almost one in four adults (24%) reported mental health concerns. Existing partnerships across local sectors can be leveraged to provide comprehensive physical and mental health services to newcomers in an emergency response.


Subject(s)
COVID-19 , Humans , Minnesota , Afghanistan , COVID-19/epidemiology , Female , Refugees , Adult , Male , Primary Health Care
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