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1.
J Health Psychol ; : 13591053241272233, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175159

RESUMEN

Despite significant advances in long COVID research, many aspects of the condition remain unknown. There is a persisting need for further research to improve the management of long COVID symptoms. This study aimed to explore the experiences and psychological needs of patients who were previously hospitalised with COVID-19, and who subsequently developed long COVID symptoms. Twelve patients with long COVID were interviewed between October 2021 and June 2022. Transcripts were analysed thematically. An overarching theme of 'Existential Crisis' was developed, incorporating three interconnecting sub-themes: 'Facing Psychological Threat', 'Seeking Legitimisation' and 'Forging a Path Through Uncertainty'. Findings suggest that the psychological impact of emergency hospitalisation for COVID-19 can be severe, particularly for those with ongoing long COVID symptoms, and that early psychological intervention should be available. Our findings also suggest the importance of further planning for future pandemics to ensure the presence of patient advocates during hospitalisation at points of critical decision-making.

2.
Crit Care ; 28(1): 246, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39014377

RESUMEN

BACKGROUND: Sepsis poses a grave threat, especially among children, but treatments are limited owing to heterogeneity among patients. We sought to test the clinical and biological relevance of pediatric septic shock subclasses identified using reproducible approaches. METHODS: We performed latent profile analyses using clinical, laboratory, and biomarker data from a prospective multi-center pediatric septic shock observational cohort to derive phenotypes and trained a support vector machine model to assign phenotypes in an internal validation set. We established the clinical relevance of phenotypes and tested for their interaction with common sepsis treatments on patient outcomes. We conducted transcriptomic analyses to delineate phenotype-specific biology and inferred underlying cell subpopulations. Finally, we compared whether latent profile phenotypes overlapped with established gene-expression endotypes and compared survival among patients based on an integrated subclassification scheme. RESULTS: Among 1071 pediatric septic shock patients requiring vasoactive support on day 1 included, we identified two phenotypes which we designated as Phenotype 1 (19.5%) and Phenotype 2 (80.5%). Membership in Phenotype 1 was associated with ~ fourfold adjusted odds of complicated course relative to Phenotype 2. Patients belonging to Phenotype 1 were characterized by relatively higher Angiopoietin-2/Tie-2 ratio, Angiopoietin-2, soluble thrombomodulin (sTM), interleukin 8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1) and lower Tie-2 and Angiopoietin-1 concentrations compared to Phenotype 2. We did not identify significant interactions between phenotypes, common treatments, and clinical outcomes. Transcriptomic analysis revealed overexpression of genes implicated in the innate immune response and driven primarily by developing neutrophils among patients designated as Phenotype 1. There was no statistically significant overlap between established gene-expression endotypes, reflective of the host adaptive response, and the newly derived phenotypes, reflective of the host innate response including microvascular endothelial dysfunction. However, an integrated subclassification scheme demonstrated varying survival probabilities when comparing patient endophenotypes. CONCLUSIONS: Our research underscores the reproducibility of latent profile analyses to identify pediatric septic shock phenotypes with high prognostic relevance. Pending validation, an integrated subclassification scheme, reflective of the different facets of the host response, holds promise to inform targeted intervention among those critically ill.


Asunto(s)
Fenotipo , Choque Séptico , Humanos , Choque Séptico/genética , Choque Séptico/clasificación , Choque Séptico/fisiopatología , Femenino , Masculino , Niño , Preescolar , Estudios Prospectivos , Lactante , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Adolescente , Estudios de Cohortes , Biomarcadores/análisis
3.
Soc Sci Med ; 355: 117112, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39029443

RESUMEN

Risk communication is a key legal and ethical component of shared decision-making. Decisions about total knee replacement, a common surgery, must contend with the fact that a minority of cases result in unintended outcomes, some of which have devastating effects. To understand how risks are communicated during decision-making, we audio-recorded and analysed 62 consultations between surgeons and patients. Various communication methods were evident, including listing risks without elaboration, discussing them in a conversational manner, abrogating discussion of risk, or using decision-tools. Discussion of risks was often brief in nature, and risk communication was sometimes curtailed or deferred by both patients and surgeons. Risks could also be observed to play a part in reinforcing policy norms of the doctor-patient relationship that highlighted patient responsibility. Nevertheless, patients and surgeons in the observed consultations appeared more interested in developing trusting relationships than in discussing risks. Because patients had sometimes experienced considerable deterioration in their knee function before their consultation, were in pain and struggled with mobility, the realities of clinical practice clashed with the policy norms of choice and patient responsibility. Rather, decisions could appear coerced by the disease process rather than being clear-cut examples of self-determination. While policy norms putatively use risk disclosure to frame communication between patients and clinicians as a transaction between customer and technician, the lack of conformity to these norms in the consultations may indicate resistance to this framing. A greater emphasis on determining positive roles for trust and care would help policy to present a nuanced understanding of decision-making. Risk communication could be seen as a factor in the formation of trusting relationships, improving its role in decision-making processes while recognising its inherent tensions with practice.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Relaciones Médico-Paciente , Confianza , Humanos , Artroplastia de Reemplazo de Rodilla/psicología , Confianza/psicología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Toma de Decisiones , Comunicación , Toma de Decisiones Conjunta , Anciano de 80 o más Años
4.
Pediatr Blood Cancer ; 71(10): e31195, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39080490

RESUMEN

BACKGROUND: Event-free survival (EFS) considers other adverse events in addition to mortality. It therefore provides a more complete understanding of the effectiveness and consequences of treatment than standard survival measures, but is rarely reported at the population level for childhood cancer. PROCEDURE: Our study cohort (n = 7067) was obtained from the Australian Childhood Cancer Registry, including children aged under 15 diagnosed with cancer between 2006 and 2015, with follow-up potentially available to 31 December 2020. The events of interest were relapse following remission, progressive disease, diagnosis of a second primary cancer or death from any cause. Five-year EFS and all-cause observed survival were both calculated, stratified by type of childhood cancer, remoteness of residence and stage at diagnosis. Differences in EFS were assessed using multivariable flexible parametric models. RESULTS: Approximately one quarter of patients (n = 1605 of 7067, 23%) experienced at least one of the events of interest within 5 years of diagnosis. Relapse was twice as common for children with metastatic/advanced disease (22%) versus children with localised/limited cancers (11%). Overall 5-year EFS was 75.0% (95% confidence interval [CI]: 73.9%-76.0%), compared to 85.8% observed survival (95% CI: 85.0%-86.6%). Patients with other gliomas had the lowest EFS (35.4%, 95% CI: 27.8%-43.1%). EFS was significantly lower among children with acute myeloid leukaemia in outer regional/remote areas compared to major cities (adjusted hazard ratio [HR] = 1.90, 95% CI: 1.20-3.00). CONCLUSIONS: Reporting EFS at a population level provides further insight on a wider range of impacts apart from mortality alone, contributing towards efforts to improve the management and outcomes of childhood cancer.


Asunto(s)
Neoplasias , Humanos , Niño , Femenino , Masculino , Preescolar , Neoplasias/mortalidad , Neoplasias/terapia , Neoplasias/patología , Australia/epidemiología , Adolescente , Lactante , Tasa de Supervivencia , Sistema de Registros , Estudios de Seguimiento , Recién Nacido , Pronóstico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología , Supervivencia sin Enfermedad
5.
BMJ Open ; 14(7): e079173, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39067879

RESUMEN

INTRODUCTION: Low back pain (LBP) is the leading global cause of disability. Patients with moderate to severe LBP who respond positively to a diagnostic medial nerve branch block can be offered radiofrequency denervation (RFD). However, high-quality evidence on the effectiveness of RFD is lacking. METHODS AND ANALYSIS: RADICAL (RADIofrequenCy denervAtion for Low back pain) is a double-blind, parallel-group, superiority randomised controlled trial. A total of 250 adults listed for RFD will be recruited from approximately 20 National Health Service (NHS) pain and spinal clinics. Recruitment processes will be optimised through qualitative research during a 12-month internal pilot phase. Participants will be randomised in theatre using a 1:1 allocation ratio to RFD or placebo. RFD technique will follow best practice guidelines developed for the trial. Placebo RFD will follow the same protocol, but the electrode tip temperature will not be raised. Participants who do not experience a clinically meaningful improvement in pain 3 months after randomisation will be offered the alternative intervention to the one provided at the outset without disclosing the original allocation. The primary clinical outcome will be pain severity, measured using a pain Numeric Rating Scale, at 3 months after randomisation. Secondary outcomes will be assessed up to 2 years after randomisation and include disability, health-related quality of life, psychological distress, time to pain recovery, satisfaction, adverse events, work outcomes and healthcare utilisation. The primary statistical analyses will be by intention to treat and will follow a prespecified analysis plan. The primary economic evaluation will take an NHS and social services perspective and estimate the discounted cost per quality-adjusted life-year and incremental net benefit of RFD over the 2-year follow-up period. ETHICS AND DISSEMINATION: Ethics approval was obtained from the London-Fulham Research Ethics Committee (21/LO/0471). Results will be disseminated in open-access publications and plain language summaries. TRIAL REGISTRATION NUMBER: ISRCTN16473239.


Asunto(s)
Análisis Costo-Beneficio , Desnervación , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Dolor de la Región Lumbar/cirugía , Dolor de la Región Lumbar/economía , Método Doble Ciego , Desnervación/métodos , Desnervación/economía , Dimensión del Dolor , Dolor Crónico/terapia , Dolor Crónico/cirugía , Calidad de Vida , Resultado del Tratamiento , Adulto
6.
PeerJ Comput Sci ; 10: e2066, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983240

RESUMEN

Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, affects transparency and reproducibility of studies, which are critical to the advancement of science. Many published studies are not reproducible due to insufficient documentation, code, and data being shared. We conducted a comprehensive analysis of 453 manuscripts published between 2016-2021 and found that 50.1% of them fail to share the analytical code. Even among those that did disclose their code, a vast majority failed to offer additional research outputs, such as data. Furthermore, only one in ten articles organized their code in a structured and reproducible manner. We discovered a significant association between the presence of code availability statements and increased code availability. Additionally, a greater proportion of studies conducting secondary analyses were inclined to share their code compared to those conducting primary analyses. In light of our findings, we propose raising awareness of code sharing practices and taking immediate steps to enhance code availability to improve reproducibility in biomedical research. By increasing transparency and reproducibility, we can promote scientific rigor, encourage collaboration, and accelerate scientific discoveries. We must prioritize open science practices, including sharing code, data, and other research products, to ensure that biomedical research can be replicated and built upon by others in the scientific community.

7.
BMJ Open ; 14(7): e085637, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986559

RESUMEN

INTRODUCTION: Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock. METHODS AND ANALYSIS: This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers. ETHICS AND DISSEMINATION: Ethics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000499785.


Asunto(s)
Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Neoplasias , Humanos , Niño , Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/efectos adversos , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Ácido Edético/uso terapéutico , Australia , Trombosis/prevención & control , Trombosis/etiología , Nueva Zelanda , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Calidad de Vida , Heparina/efectos adversos , Heparina/administración & dosificación , Heparina/uso terapéutico
8.
Am J Respir Crit Care Med ; 210(4): 455-464, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38913573

RESUMEN

Rationale: Idiopathic pulmonary fibrosis (IPF) causes irreversible fibrosis of the lung parenchyma. Although antifibrotic therapy can slow IPF progression, treatment response is variable. There exists a critical need to develop a precision medicine approach to IPF. Objectives: To identify and validate biologically driven molecular endotypes of IPF. Methods: Latent class analysis (LCA) was independently performed in prospectively recruited discovery (n = 875) and validation (n = 347) cohorts. Twenty-five plasma biomarkers associated with fibrogenesis served as class-defining variables. The association between molecular endotype and 4-year transplant-free survival was tested using multivariable Cox regression adjusted for baseline confounders. Endotype-dependent differential treatment response to future antifibrotic exposure was then assessed in a pooled cohort of patients naive to antifibrotic therapy at the time of biomarker measurement (n = 555). Measurements and Main Results: LCA independently identified two latent classes in both cohorts (P < 0.0001). WFDC2 (WAP four-disulfide core domain protein 2) was the most important determinant of class membership across cohorts. Membership in class 2 was characterized by higher biomarker concentrations and a higher risk of death or transplant (discovery, hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.64-2.48; P < 0.001; validation, HR, 1.95; 95% CI, 1.34-2.82; P < 0.001). In pooled analysis, significant heterogeneity in treatment effect was observed between endotypes (P = 0.030 for interaction), with a favorable antifibrotic response in class 2 (HR, 0.64; 95% CI, 0.45-0.93; P = 0.018) but not in class 1 (HR, 1.19; 95% CI, 0.77-1.84; P = 0.422). Conclusions: In this multicohort study, we identified two novel molecular endotypes of IPF with divergent clinical outcomes and responses to antifibrotic therapy. Pending further validation, these endotypes could enable a precision medicine approach for future IPF clinical trials.


Asunto(s)
Biomarcadores , Fibrosis Pulmonar Idiopática , Análisis de Clases Latentes , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Estudios de Cohortes , Estudios Prospectivos
9.
bioRxiv ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38915582

RESUMEN

Single-particle tracking demonstrates that individual filaments in bundles of vimentin intermediate filaments are transported in the cytoplasm by motor proteins along microtubules. Furthermore, using 3D FIB-SEM the authors showed that vimentin filament bundles are loosely packed and coaligned with microtubules. Vimentin intermediate filaments (VIFs) form complex, tight-packed networks; due to this density, traditional ensemble labeling and imaging approaches cannot accurately discern single filament behavior. To address this, we introduce a sparse vimentin-SunTag labeling strategy to unambiguously visualize individual filament dynamics. This technique confirmed known long-range dynein and kinesin transport of peripheral VIFs and uncovered extensive bidirectional VIF motion within the perinuclear vimentin network, a region we had thought too densely bundled to permit such motility. To examine the nanoscale organization of perinuclear vimentin, we acquired high-resolution electron microscopy volumes of a vitreously frozen cell and reconstructed VIFs and microtubules within a ~50 µm3 window. Of 583 VIFs identified, most were integrated into long, semi-coherent bundles that fluctuated in width and filament packing density. Unexpectedly, VIFs displayed minimal local co-alignment with microtubules, save for sporadic cross-over sites that we predict facilitate cytoskeletal crosstalk. Overall, this work demonstrates single VIF dynamics and organization in the cellular milieu for the first time.

10.
Nat Med ; 30(7): 1913-1922, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38844796

RESUMEN

Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931.


Asunto(s)
Neoplasias , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Niño , Neoplasias/genética , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Femenino , Masculino , Adolescente , Preescolar , Lactante , Supervivencia sin Progresión , Resultado del Tratamiento
11.
Nature ; 630(8017): 671-676, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38867039

RESUMEN

The subpectoral diverticulum (SPD) is an extension of the respiratory system in birds that is located between the primary muscles responsible for flapping the wing1,2. Here we survey the pulmonary apparatus in 68 avian species, and show that the SPD was present in virtually all of the soaring taxa investigated but absent in non-soarers. We find that this structure evolved independently with soaring flight at least seven times, which indicates that the diverticulum might have a functional and adaptive relationship with this flight style. Using the soaring hawks Buteo jamaicensis and Buteo swainsoni as models, we show that the SPD is not integral for ventilation, that an inflated SPD can increase the moment arm of cranial parts of the pectoralis, and that pectoralis muscle fascicles are significantly shorter in soaring hawks than in non-soaring birds. This coupling of an SPD-mediated increase in pectoralis leverage with force-specialized muscle architecture produces a pneumatic system that is adapted for the isometric contractile conditions expected in soaring flight. The discovery of a mechanical role for the respiratory system in avian locomotion underscores the functional complexity and heterogeneity of this organ system, and suggests that pulmonary diverticula are likely to have other undiscovered secondary functions. These data provide a mechanistic explanation for the repeated appearance of the SPD in soaring lineages and show that the respiratory system can be co-opted to provide biomechanical solutions to the challenges of flight and thereby influence the evolution of avian volancy.


Asunto(s)
Vuelo Animal , Halcones , Respiración , Sistema Respiratorio , Alas de Animales , Animales , Evolución Biológica , Fenómenos Biomecánicos/fisiología , Vuelo Animal/fisiología , Halcones/anatomía & histología , Halcones/clasificación , Halcones/fisiología , Pulmón/anatomía & histología , Pulmón/fisiología , Modelos Biológicos , Músculo Esquelético/anatomía & histología , Músculo Esquelético/fisiología , Sistema Respiratorio/anatomía & histología , Alas de Animales/fisiología , Alas de Animales/anatomía & histología , Masculino , Femenino
12.
Res Q Exerc Sport ; : 1-11, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941624

RESUMEN

To determine the effect of immersive virtual reality use on finishing time of a vigorous-intensity self-regulated exercise task, and on relevant psychological variables. Healthy untrained adults (N = 21; 10 men/11 women; age = 22.9 ± 7.2 years; BMI = 24.0 ± 4.5 kg/m2) completed 1500-m exercise bouts on a rowing ergometer in a counterbalanced and randomized order, with and without use of a headset-delivered virtual reality fitness program. Heart rate, rating of perceived exertion, affective valence, and attentional focus were collected every 300 m, in addition to finishing time. Data were analyzed with repeated measures as appropriate. Intensity of both exercise bouts was considered vigorous according to heart rate results (>77% maximal heart rate). Finishing time was faster in the control condition (449.57 ± 82.39 s) than in the virtual reality condition (463.00 ± 91.78 s), p = .007. Compared to the control condition, the virtual reality condition was characterized by a more external attentional focus (52.38 ± 18.22 vs. 38.76 ± 17.81, p < .001). No differences were observed for remaining variables as a result of condition (p > .05 for all). When a headset-delivered VR program was used during a self-regulated vigorous-intensity exercise task, participants were 13.6 seconds (~3%) slower than in a control condition. Attentional focus was manipulated to be more external with VR use, which may have ultimately distracted from the exercise objective. Recommendations for selecting an appropriate virtual reality experience for a given exercise task are discussed.

13.
J Am Coll Emerg Physicians Open ; 5(3): e13192, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38887225

RESUMEN

Objectives: Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission to hospital wards with subsequent transfer to intensive care unit (ICU) is associated with worse outcomes. We hypothesized that initial admission to the ward may affect outcomes in patient with COVID-19 ARDS. Methods: This was a retrospective study of consecutive adults admitted for COVID-19 ARDS between March 2020 and March 2021 at Stanford Health Care. Mortality scores at hospital admission (Coronavirus Clinical Characterization Consortium Mortality Score [4C score]) and ICU admission (Simplified Acute Physiology Score III [SAPS-III]) were calculated, as well as ROX index for patients on high flow nasal oxygen. Patients were classified by emergency department (ED) disposition (ward-first vs. ICU-direct), and 28- and 60-day mortality and highest level of respiratory support within 1 day of ICU admission were compared. A second cohort (April 2021‒July 2022, n = 129) was phenotyped to validate mortality outcome. Results: A total of 157 patients were included, 48% of whom were first admitted to the ward (n = 75). Ward-first patients had more comorbidities, including lung disease. Ward-first patients had lower 4C and similar SAPS-III score, yet increased mortality at 28 days (32% vs. 17%, hazard ratio [HR] 2.0, 95% confidence interval [95% CI] 1.0‒3.7, p = 0.039) and 60 days (39% vs. 23%, HR 1.83, 95% CI 1.04‒3.22, p = 0.037) compared to ICU-direct patients. More ward-first patients escalated to mechanical ventilation on day 1 of ICU admission (36% vs. 14%, p = 0.002) despite similar ROX index. Ward-first patients who upgraded to ICU within 48 h of ED presentation had the highest mortality. Mortality findings were replicated in a sensitivity analysis. Conclusion: Despite similar baseline risk scores, ward-first patients with COVID-19 ARDS had increased mortality and escalation to mechanical ventilation compared to ICU-direct patients. Ward-first patients requiring ICU upgrade within 48 h were at highest risk, highlighting a need for improved identification of this group at ED admission.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38791786

RESUMEN

Sleep is often impaired in firefighters due to the psychologically and physiologically intense nature of their work and working shift schedules. Peanut butter is affordable and a substantial source of monounsaturated fatty acids, which may aid sleep health. Thus, this study sought to determine if a daily serving of peanut butter consumed before bedtime for seven weeks altered sleep quality and quantity among full-time firefighters. Forty firefighters (peanut butter group = 20; control group = 20) participated in this eight-week randomized controlled trial. All participants completed a subjective questionnaire on mood, focus, and alertness twice daily and wore an Actigraph wristwatch to measure sleep variables, including latency, efficiency, time in bed, time asleep, wake after sleep onset, number of awakenings, and time spent awake. After a baseline week, the peanut butter group consumed two tablespoons of peanut butter two hours prior to bedtime for seven weeks. Compared to the control group, the peanut butter group did not demonstrate significant changes (p > 0.05) in sleep measures or subjective feelings of mood, focus, or alertness after consuming peanut butter for seven weeks. Therefore, peanut butter as a source of peanuts did not alter sleep quality or quantity in this group of firefighters.


Asunto(s)
Arachis , Bomberos , Sueño , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad
15.
Proc Natl Acad Sci U S A ; 121(23): e2308531121, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38805288

RESUMEN

Many animals exhibit remarkable colors that are produced by the constructive interference of light reflected from arrays of intracellular guanine crystals. These animals can fine-tune their crystal-based structural colors to communicate with each other, regulate body temperature, and create camouflage. While it is known that these changes in color are caused by changes in the angle of the crystal arrays relative to incident light, the cellular machinery that drives color change is not understood. Here, using a combination of 3D focused ion beam scanning electron microscopy (FIB-SEM), micro-focused X-ray diffraction, superresolution fluorescence light microscopy, and pharmacological perturbations, we characterized the dynamics and 3D cellular reorganization of crystal arrays within zebrafish iridophores during norepinephrine (NE)-induced color change. We found that color change results from a coordinated 20° tilting of the intracellular crystals, which alters both crystal packing and the angle at which impinging light hits the crystals. Importantly, addition of the dynein inhibitor dynapyrazole-a completely blocked this NE-induced red shift by hindering crystal dynamics upon NE addition. FIB-SEM and microtubule organizing center (MTOC) mapping showed that microtubules arise from two MTOCs located near the poles of the iridophore and run parallel to, and in between, individual crystals. This suggests that dynein drives crystal angle change in response to NE by binding to the limiting membrane surrounding individual crystals and walking toward microtubule minus ends. Finally, we found that intracellular cAMP regulates the color change process. Together, our results provide mechanistic insight into the cellular machinery that drives structural color change.


Asunto(s)
Pez Cebra , Animales , Norepinefrina/metabolismo , Norepinefrina/farmacología , Color , Pigmentación/fisiología , Microscopía Electrónica de Rastreo , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/química
17.
Curr Opin Cell Biol ; 88: 102364, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692079

RESUMEN

First identified in dividing cells as revolving clusters of actin filaments, these are now understood as mitochondrially-associated actin waves that are active throughout the cell cycle. These waves are formed from the polymerization of actin onto a subset of mitochondria. Within minutes, this F-actin depolymerizes while newly formed actin filaments assemble onto neighboring mitochondria. In interphase, actin waves locally fragment the mitochondrial network, enhancing mitochondrial content mixing to maintain organelle homeostasis. In dividing cells actin waves spatially mix mitochondria in the mother cell to ensure equitable partitioning of these organelles between daughter cells. Progress has been made in understanding the consequences of actin cycling as well as the underlying molecular mechanisms, but many questions remain, and here we review these elements. Also, we draw parallels between mitochondrially-associated actin cycling and cortical actin waves. These dynamic systems highlight the remarkable plasticity of the actin cytoskeleton.


Asunto(s)
Citoesqueleto de Actina , Actinas , Homeostasis , Mitocondrias , Mitocondrias/metabolismo , Actinas/metabolismo , Humanos , Animales , Citoesqueleto de Actina/metabolismo , Orgánulos/metabolismo
18.
Artículo en Inglés | MEDLINE | ID: mdl-38734373

RESUMEN

Patient registries are a mechanism for collecting data on allergic and immunologic diseases that provide important information on epidemiology and outcomes that can ultimately improve patient care. Key criteria for establishing effective registries include the use of a clearly defined purpose, identifying the target population and ensuring consistent data collection. Registries in allergic diseases include those for diseases such as inborn errors of immunity (IEI), food allergy, asthma and anaphylaxis, pharmacological interventions in vulnerable populations, and adverse effects of pharmacologic interventions including hypersensitivity reactions to drugs and vaccines. Important insights gained from patient registries in our field include contributions in phenotype and outcomes in IEI, the risk for adverse reactions in food-allergic patients in multiple settings, the benefits and risk of biologic medications for asthma during pregnancy, vaccine safety, and the categorization and genetic determination of risk for severe cutaneous adverse reactions to medications. Impediments to the development of clinically meaningful patient registries include the lack of funding resources for registry establishment and the quality, quantity, and consistency of available data. Despite these drawbacks, high-quality and successful registries are invaluable in informing clinical practice and improving outcomes in patients with allergic and immunological diseases.

19.
Nat Commun ; 15(1): 3793, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714822

RESUMEN

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.


Asunto(s)
Actinas , Homeostasis , Interfase , Mitocondrias , Dinámicas Mitocondriales , Actinas/metabolismo , Mitocondrias/metabolismo , Humanos , Forminas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células HeLa , Microtúbulos/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Animales
20.
J Thorac Imaging ; 39(5): 304-311, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38662632

RESUMEN

PURPOSE: The objective of this study is to identify and detail the radiologic manifestations of surgical site and disseminated Mycobacterium chimaera ( MC) infection. The aim is to facilitate early identification and diagnosis of MC, considering its indolent nature and the challenges involved in clinically and pathologically establishing the diagnosis. PATIENTS AND METHODS: This was a retrospective cohort study reviewing computed tomography (CT), positron emission tomography (PET)/CT, and magnetic resonance imaging examinations in patients over the age of 18 years with a history of open heart surgery and a clinical or pathologic diagnosis of MC. Two radiology residents, a fellowship-trained nuclear medicine radiologist, and a fellowship-trained cardiothoracic radiologist performed consensus reads to determine the imaging findings seen in MC infection. RESULTS: Twenty-five patients were included. Localized, surgical site infection was more common than disseminated disease. Typical CT findings included peristernal soft tissue thickening, sinus tracts often extending to the cutaneous surface, slowly enlarging fluid collections, and sternal osteolysis. PET/CT findings demonstrated hypermetabolic activity in nearly all patients localized to sites of infection. Imaging findings for disseminated infection included hepatosplenomegaly, lymphadenopathy, involvement of the central nervous system, discitis/osteomyelitis, and distant abscesses. CONCLUSIONS: Imaging plays a vital role in suggesting possible surgical sites and disseminated MC infection acquired from open heart surgery. Radiologists must keep a high index of suspicion given the indolent nature and subtle imaging change over time. PET/CT is most useful in diagnosis and helps in differentiating between a sterile postoperative fluid collection or scarring and active MC infection and helps provide a target for debridement.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tomografía Computarizada por Rayos X/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adulto , Mycobacterium , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infección de la Herida Quirúrgica/diagnóstico por imagen , Estudios de Cohortes , Infecciones por Mycobacterium/diagnóstico por imagen , Anciano de 80 o más Años
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