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1.
Gynecol Oncol Rep ; 53: 101408, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38774769

RESUMEN

•The presence of concomitant non-reducible prolapse and cervical cancer is rare.•Treatment of cervical cancer complicated by non-reducible prolapse must be individualized.•The role prolapse may play in the development of HPV-negative cervical cancer is unclear.

2.
iScience ; 27(4): 109546, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38577107

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous immune population with diverse immunosuppressive functions in solid tumors. Here, we explored the role of the tumor microenvironment in regulating MDSC differentiation and immunosuppressive properties via signal-regulatory protein alpha (SIRPα)/CD47 signaling. In a murine melanoma model, we observed progressive increases in monocytic MDSCs and monocyte-derived dendritic cells that exhibited potent T cell-suppressive capabilities. These adaptations could be recapitulated in vitro by exposing hematopoietic stem cells to tumor-derived factors. Engagement of CD47 with SIRPα on myeloid cells reduced their phagocytic capability, enhanced expression of immune checkpoints, increased reactive oxygen species production, and suppressed T cell proliferation. Perturbation of SIRPα signaling restored phagocytosis and antigen presentation by MDSCs, which was accompanied by renewed T cell activity and delayed tumor growth in multiple solid cancers. These data highlight that therapeutically targeting myeloid functions in combination with immune checkpoint inhibitors could enhance anti-tumor immunity.

3.
Nat Commun ; 15(1): 1394, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374174

RESUMEN

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.


Asunto(s)
Bursitis , Humanos , Tirosina Quinasa c-Mer/metabolismo , Inflamación/metabolismo , Membrana Sinovial/metabolismo , Fibrosis
4.
Mol Microbiol ; 121(5): 882-894, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38372181

RESUMEN

The sole unifying feature of the incredibly diverse Archaea is their isoprenoid-based ether-linked lipid membranes. Unique lipid membrane composition, including an abundance of membrane-spanning tetraether lipids, impart resistance to extreme conditions. Many questions remain, however, regarding the synthesis and modification of tetraether lipids and how dynamic changes to archaeal lipid membrane composition support hyperthermophily. Tetraether membranes, termed glycerol dibiphytanyl glycerol tetraethers (GDGTs), are generated by tetraether synthase (Tes) by joining the tails of two bilayer lipids known as archaeol. GDGTs are often further specialized through the addition of cyclopentane rings by GDGT ring synthase (Grs). A positive correlation between relative GDGT abundance and entry into stationary phase growth has been observed, but the physiological impact of inhibiting GDGT synthesis has not previously been reported. Here, we demonstrate that the model hyperthermophile Thermococcus kodakarensis remains viable when Tes (TK2145) or Grs (TK0167) are deleted, permitting phenotypic and lipid analyses at different temperatures. The absence of cyclopentane rings in GDGTs does not impact growth in T. kodakarensis, but an overabundance of rings due to ectopic Grs expression is highly fitness negative at supra-optimal temperatures. In contrast, deletion of Tes resulted in the loss of all GDGTs, cyclization of archaeol, and loss of viability upon transition to the stationary phase in this model archaea. These results demonstrate the critical roles of highly specialized, dynamic, isoprenoid-based lipid membranes for archaeal survival at high temperatures.


Asunto(s)
Lípidos de la Membrana , Thermococcus , Lípidos de la Membrana/metabolismo , Thermococcus/metabolismo , Thermococcus/genética , Éteres de Glicerilo/metabolismo , Proteínas Arqueales/metabolismo , Archaea/metabolismo , Lípidos/química
5.
Artículo en Inglés | MEDLINE | ID: mdl-38272658

RESUMEN

There are no internationally agreed descriptors for categories of neonatal transports which facilitate comparisons between settings. To continually review and enhance neonatal transport care we need robust categories to develop benchmarks. This review aimed to report on the development and application of key measures across a national neonatal transport service. The UK Neonatal Transport Group (UK-NTG) developed a core dataset and benchmarks for transported infants and collected annual national data. Data were reported back to teams to allow benchmarking and improvements. From 2012 to 2021, the rate of UK neonatal transfers increased from 18 to 22/1000 live births despite a falling birth rate. Neonatal transfers on nitric oxide increased until 2016 before plateauing. The proportion of transport services able to provide high frequency oscillation and servo-controlled therapeutic hypothermia increased over the study period. High-flow nasal cannula oxygen use increased, becoming the most frequently used non-invasive respiratory support mode. For infants <27 weeks of gestational age, transfers for uplift of care in the first 3 days of life have fallen from 420 (2016) to 288 (2020/2021) and for lack of neonatal capacity from 24 (2016) to 2 (2020/2021). The rate of ventilated infants completing transfer with CO2 out of the benchmark range varied from 9% to 13% with marked variation between transport services' rates of hypocapnia (0-10%) and hypercapnia with acidosis (0-9%). The development of the UK-NTG dataset supports national tracking of activity and clinical trends allowing comparison of patient-focused benchmarks across teams.

6.
J Pediatr Surg ; 59(2): 305-309, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38030532

RESUMEN

AIM: Paediatric-preoperative anaemia management is challenging in settings where clinical judgment is used to diagnose anaemia owing to a lack of timely, affordable preoperative haemoglobin testing. We analysed anaemia management in such a setting after the introduction of point-of-care bedside haemoglobin testers. METHOD: 1033 children who underwent surgery at a hospital in Bangladesh were included in this study. 569 underwent major surgery, and 464 underwent minor surgery and belonged to predominantly ASA category 1 or 2. RESULTS: 940/1033 children underwent preoperative anaemia testing. Average haemoglobin was 11.7 g/dL. 103/1033 children were deemed clinically anaemic. However, 285 children were found to have anaemia based on bedside testing. Sensitivity of clinical judgement was 33.68% (95 % CI 28.22%-39.49%), and the specificity was 99.08% (95 % CI 98.02%-99.66%). 63/1033 had preoperative anaemia treatment, of whom 60 underwent transfusion. Subgroup analysis of children with haemoglobin <10 g/dL (n = 124) was done to compare conservative vs liberal transfusion strategy. 43/124 of this subset was transfused. Average length of stay for those transfused was 11.7 days, and those who weren't was 9.9 days (p = 0.087). 4 patients in the transfused subgroup required post-op ICU, and only 1 patient in the conservatively managed arm required ICU (p = 0.048). CONCLUSION: This study demonstrates the positive impact of bedside haemoglobin testers as they have resulted in a significantly higher proportion of children diagnosed with anaemia at a fraction of the cost and logistics involved in laboratory testing. Further research on haemoglobin thresholds is required to understand the safety and long-term impact of restrictive transfusion in the surgical context. LEVEL OF EVIDENCE: 2c (Grading as per the Oxford Centre for Evidence Based Medicine).


Asunto(s)
Anemia , Transfusión de Eritrocitos , Humanos , Niño , Anemia/diagnóstico , Anemia/etiología , Anemia/terapia , Hemoglobinas/análisis , Transfusión Sanguínea , Estudios Prospectivos
7.
Obstet Med ; 16(4): 217-221, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38074210

RESUMEN

Background: Pregnancy in women with cystic fibrosis (CF) is becoming more common. Long-term metabolic issues such as diabetes are also becoming more common and have potentially important impacts on pregnancy outcomes. This study aimed to assess the impact of diabetes on pregnancy outcomes for women with CF. Methods: We undertook a retrospective chart audit of pregnancies to women with CF at the two tertiary obstetric hospitals in Southeast Queensland associated with CF and transplant management clinics between 2006 and 2016. Results: A total of 38 pregnancies among 26 women were identified. Four women (five pregnancies) had cystic fibrosis-related diabetes (CFRD) diagnosed prior to pregnancy, and 12 women (15 pregnancies) developed gestational diabetes (GDM) complicating pregnancy. CFRD and GDM were associated with higher rates of delivery complications, prematurity, and the need for neonatal intensive care unit admission. Conclusion: Diabetes is common during pregnancy in women with CF and impacts pregnancy outcomes.

8.
Science ; 380(6649): 1059-1064, 2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37289888

RESUMEN

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.


Asunto(s)
Migración Animal , Animales Salvajes , COVID-19 , Mamíferos , Cuarentena , Animales , Humanos , Animales Salvajes/fisiología , Animales Salvajes/psicología , COVID-19/epidemiología , Mamíferos/fisiología , Mamíferos/psicología , Movimiento
9.
Aust N Z J Obstet Gynaecol ; 63(5): 714-720, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37221081

RESUMEN

BACKGROUND: Previously, management of gestational diabetes (GDM) has focused largely on glycaemic control, with a view to reduce the occurrence of large-for-gestational-age (LGA) infants. However, tight glycaemic control in GDM is associated with a higher incidence of small-for-gestational-age (SGA) infants, which has been linked to higher rates of adverse outcomes. AIM: The aim was to characterise risk factors associated with having an SGA infant in women being treated for GDM. METHODS: This was a retrospective observational cohort study of 308 women with GDM. Women were split into groups based on their infant's size at delivery (SGA, appropriate-for-gestational-age (AGA) or LGA). Literature review and expert opinion helped to determine several predictors of women with GDM delivering an SGA infant, and statistical analysis was used to produce odds ratios (OR) for these predictors. RESULTS: The sample included primiparous women with a mean pre-pregnancy body mass index (BMI) of 25.72 (standard deviation: 5.75). Metabolic risk factors associated with delivering an SGA infant included a lower pre-pregnancy BMI (adjusted OR 1.13, P = 0.04, 95% confidence interval (CI): 1.01-1.26), a lower fasting blood glucose level (BGL) (adjusted OR: 3.21, P = 0.01, 95% CI: 1.30-7.93) and growth that was high risk for SGA at baseline ultrasound scan (USS) (adjusted OR: 7.43, P < 0.001, 95% CI: 2.93-18.79). CONCLUSIONS: The combined clinical picture of lower pre-pregnancy BMI, fasting BGL and baseline USS growth measurements may indicate a need for less aggressive glucose management in women with GDM to prevent SGA infants.

10.
Med J Aust ; 218(10): 460-466, 2023 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-37087105

RESUMEN

OBJECTIVES: To examine the clinical characteristics and short term outcomes for children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who presented to Australian hospitals during 2020 and 2021. DESIGN, SETTING: Retrospective case review study in nineteen hospitals of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network from all Australian states and territories, including seven major paediatric tertiary centres and eight Victorian hospitals. PARTICIPANTS: SARS-CoV-2-positive people under 18 years of age who attended emergency departments or were admitted to hospital during 1 February 2020 - 31 December 2021. MAIN OUTCOME MEASURES: Epidemiological and clinical characteristics, by hospital care type (emergency department [ED] or inpatient care). RESULTS: A total of 1193 SARS-CoV-2-positive children and adolescents (527 girls, 44%) attended the participating hospitals (107 in 2020, 1086 in 2021). Their median age was 3.8 years (interquartile range [IQR], 0.8-11.4 years); 63 were Aboriginal or Torres Strait Islander people (5%). Other medical conditions were recorded for 293 children (25%), including asthma (86, 7%) and premature birth (68, 6%). Medical interventions were not required during 795 of 1181 ED presentations (67%); children were discharged directly home in 764 cases (65%) and admitted to hospital in 282 (24%; sixteen to intensive care units). The 384 admissions to hospital (including 102 direct admissions) of 341 children (25 infants under one month of age) included 23 to intensive care (6%); the median length of stay was three days (IQR, 1-9 days). Medical interventions were not required during 261 admissions (68%); 44 children received respiratory support (11%) and 21 COVID-19-specific treatments, including antiviral and biologic agents (5%). Being under three months of age (v one year to less than six years: odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7-4.0) and pre-existing medical conditions (OR, 2.5; 95% CI, 1.9-3.2) were the major predictors of hospital admission. Two children died, including one without a known pre-existing medical condition. CONCLUSION: During 2020 and 2021, most SARS-CoV-2-positive children and adolescents who presented to participating hospitals could be managed as outpatients. Outcomes were generally good, including for those admitted to hospital.


Asunto(s)
COVID-19 , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Australia/epidemiología , COVID-19/epidemiología , COVID-19/terapia , Servicio de Urgencia en Hospital , Hospitales , Estudios Retrospectivos , SARS-CoV-2 , Masculino
11.
Cancer Res Commun ; 3(2): 215-222, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36817949

RESUMEN

Healthcare access and health behaviors differ between those living in urban and rural communities and contribute to inequitable cancer health outcomes. The COVID-19 pandemic led to significant disruptions in daily life and healthcare delivery. This cross-sectional survey aimed to measure the impact of the COVID-19 pandemic on the health behaviors of cancer patients and survivors, comparing outcomes for urban and rural respondents. Survey was administered from January 2021-June 2021 to cancer patients or survivors (treated within the last 5 years) at one of six cancer centers in Washington and Idaho. Respondent ZIP code was used to assess rurality using Rural-Urban Commuting Area designation. 515 rural (43.5% of those contacted) and 146 urban (40% of those contacted) cancer patients and survivors participated. Few differences between urban and rural cancer patients and cancer survivors were noted. Rural residents were older (69.2 years vs. 66.9 years). Rural respondents had higher mean alcohol consumption than urban respondents (4.4 drinks per week vs. 2.7 drinks per week). 12.2% of those who reported drinking in the last 30 days also reported increased alcohol consumption since the start of the pandemic, with no difference in reported increased alcohol consumption in rural vs. urban respondents. 38.5% reported decreased physical activity. 20.5% reported cancelling or delaying cancer care due to the COVID-19 pandemic. Delays in cancer healthcare services and worsening health behaviors due to the COVID-19 pandemic may contribute to poorer health outcomes, with few differences between rural and urban cancer patients and cancer survivors.


Asunto(s)
COVID-19 , Supervivientes de Cáncer , Neoplasias , Humanos , Pandemias , Población Rural , Estudios Transversales , Población Urbana , COVID-19/epidemiología , Conductas Relacionadas con la Salud , Neoplasias/epidemiología , Aceptación de la Atención de Salud , Accesibilidad a los Servicios de Salud
12.
Am Heart J ; 259: 79-86, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36796572

RESUMEN

BACKGROUND: Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarction (STEMI). We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. METHODS AND RESULTS: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs or placebo / control as part of 4 randomized clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot, the multicenter French BONAMI trial and SWISS-AMI trials. A total of 327 patients had paired imaging data at 1 year. All patients received 100 to 150 million intracoronary autologous BMCs or placebo / control 3 to 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n = 210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n = 146) (P < .01). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7%; P < .05). Similarly, left-ventricular end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) demonstrated significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo. In contrast, no improvement in LVEF or LV volumes was observed in those patients without MVO who received BMCs compared to placebo. CONCLUSIONS: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who benefit from intracoronary stem cell therapy.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Disfunción Ventricular Izquierda , Humanos , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/complicaciones , Volumen Sistólico , Infarto del Miocardio/complicaciones , Trasplante de Médula Ósea/métodos , Disfunción Ventricular Izquierda/complicaciones , Resultado del Tratamiento
13.
Blood ; 141(11): 1316-1321, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36493342

RESUMEN

Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic mutations of individual stem cells, progenitors (common myeloid progenitors, granulocyte monocyte progenitors, and megakaryocyte erythroid progenitors), and matched circulating hematopoietic cells (monocytes, neutrophils, and naïve B cells) in MDS and CMML were characterized via high-throughput single-cell genotyping, followed by bulk analysis in immature and mature cells before and after AZA treatment. The mutational burden was similar throughout differentiation, with even the most mutated stem and progenitor clones maintaining their capacity to differentiate to mature cell types in vivo. Increased contributions from productive mutant progenitors appear to underlie improved hematopoiesis in MDS following HMA therapy.


Asunto(s)
Leucemia Mielomonocítica Crónica , Síndromes Mielodisplásicos , Humanos , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/metabolismo , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Células Madre Hematopoyéticas/metabolismo , Monocitos , Células Clonales
14.
Crisis ; 44(4): 349-360, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36073206

RESUMEN

Background: Befriending is one of many strategies with the potential to reduce suicidal ideation and decrease the risk of suicide. Aims: To measure change in suicidal ideation and behavior among visitors (service users) supported at The Listening Place (TLP), a charity which offers volunteer-run, face-to-face befriending to people who are suicidal. Method: This study was peer reviewed and preregistered on the Open Science Framework prior to data extraction. Anonymized data were extracted for visitors at the point of referral and after 3 months of receiving support. Paired-sample tests were used to test whether self-reported suicidal ideation and behaviors changed after 3 months of support from TLP. Multivariable regressions were used to test whether change in suicidal feelings was associated with demographic characteristics or baseline self-reported suicidality. Results: TLP received 13,938 referrals from July 2016 to February 2022. Self-reported suicidal ideation, suicidal behavior, and feelings of distress decreased after 3 months, while feelings of support increased. Only self-reported suicidal behavior prior to referral was associated with a lesser reduction in self-reported suicidality after 3 months. Limitations: In the absence of a control group, it cannot be concluded that TLP causes the reduction in self-reported suicidality. Conclusions: An empathetic, nonjudgmental, listening service for people who are feeling suicidal was well received by users, who experienced a reduction in suicidality.


Asunto(s)
Ideación Suicida , Suicidio , Humanos , Emociones , Factores de Riesgo
15.
Cureus ; 14(10): e30081, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36381826

RESUMEN

Ocular involvement is commonly seen in systemic lupus erythematosus (SLE). However, chorioretinopathy is an easily missed ocular manifestation of SLE. Early recognition and a multidisciplinary treatment approach can play a key role in reducing the ocular and systemic morbidity seen with this condition. This case report describes a patient with active SLE who presented with bilateral lupus chorioretinopathy. The patient demonstrated a significant improvement in ocular symptoms once the systemic disease was controlled.

16.
Gynecol Oncol Rep ; 44: 101099, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36388757

RESUMEN

•Mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma is extremely rare.•It is important to differentiate the gastrointestinal-type adenocarcinoma arising along with neuroendocrine tumor from a primary mucinous adenocarcinoma of the ovary. SATB2 and CDX2 Immunohistochemical stains play important role in differentiate these two.•This case highlights the careful morphologic evaluation and extensive sampling is crucial to make this rare diagnosis.

17.
Am J Physiol Heart Circ Physiol ; 323(4): H818-H824, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36083798

RESUMEN

Microvascular obstruction (MVO) frequently develops after ST-elevation myocardial infarction (STEMI) and is associated with increased mortality and adverse left ventricular remodeling. We hypothesized that increased extravascular compressive forces in the myocardium that arise from the development of myocardial edema because of ischemia-reperfusion injury would contribute to the development of MVO. We measured MVO, infarct size, and left ventricular mass in patients with STEMI (n = 385) using cardiac MRI 2 to 3 days following successful percutaneous coronary intervention and stenting. MVO was found in 57% of patients with STEMI. The average infarct size was 45 ± 29 g. Patients with MVO had significantly greater infarct size and reduced left ventricular (LV) function (P < 0.01) compared with patients without MVO. Patients with MVO had significantly greater LV mass than patients without MVO and there was a linear increase in MVO with increasing LV mass (P < 0.001). Myocardial edema by T2-weighted imaging increased with increasing LV mass and patients with MVO had significantly greater myocardial edema than patients without MVO (P < 0.01). Patients with MVO had significantly greater left ventricular end-diastolic pressure (LVEDP) than patients without MVO (P < 0.05). In a cohort of patients with STEMI who underwent primary percutaneous intervention, we observed that MVO increased linearly with increasing LV mass and was associated with increased myocardial edema and higher LVEDP. These observations support the concept that extravascular compressive forces in the left ventricle may increase with increasing ischemic injury and contribute to the development of MVO.NEW & NOTEWORTHY Patients with STEMI (n = 385) had cardiac MRIs 2 to 3 days following reperfusion with primary PCI to determine the relationship between myocardial edema, LV mass, and MVO. We observed that MVO increased linearly with LV mass and that myocardial edema measured by T2-imaging also increased linearly with LV mass. Patients with MVO had greater edema and LVEDP than subjects without MVO. These findings suggest that myocardial edema which arises from ischemia-reperfusion injury may result in extravascular compression of the microcirculation manifested as MVO on cardiac MRI.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Daño por Reperfusión , Infarto del Miocardio con Elevación del ST , Circulación Coronaria , Edema/diagnóstico por imagen , Humanos , Microcirculación , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Miocardio , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Daño por Reperfusión/complicaciones , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Resultado del Tratamiento
18.
Nat Commun ; 13(1): 4678, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35945222

RESUMEN

There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here we present iLINCS ( http://ilincs.org ), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The platform facilitates mining and re-analysis of the large collection of omics datasets (>34,000), pre-computed signatures (>200,000), and their connections, as well as the analysis of user-submitted omics signatures of diseases and cellular perturbations. iLINCS analysis workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. iLINCS user-friendly interfaces enable execution of sophisticated analyses of omics signatures, mechanism of action analysis, and signature-driven drug repositioning. We illustrate the utility of iLINCS with three use cases involving analysis of cancer proteogenomic signatures, COVID 19 transcriptomic signatures and mTOR signaling.


Asunto(s)
COVID-19 , Neoplasias , COVID-19/genética , Biología Computacional , Humanos , Neoplasias/genética , Programas Informáticos , Transcriptoma , Flujo de Trabajo
19.
Int J Cardiol ; 366: 25-29, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35817202

RESUMEN

BACKGROUND: Microvascular obstruction (MVO) contributes significantly to adverse left-ventricular remodeling and mortality following ST-segment elevation myocardial infarction (STEMI). Because circadian processes contribute significantly to the timing and degree of ischemic injury in STEMI we hypothesized that the occurrence of MVO may also exhibit circadian behavior. METHODS AND RESULTS: A single center cohort trial of 336 STEMI patients (273 M 63 F) with their first STEMI who were reperfused with primary percutaneous coronary intervention (PCI) and referred for cardiac MRI prior to discharge. The time of onset of chest pain was recorded from the patients chart and used to stratify patients with MVO over a 24-h cycle to analyze for circadian behavior. Subjects with MVO (n = 200) had greater infarct size by cMRI (45 vs. 20 g; p < 0.001), had reduced ejection fraction (LVEF = 50 vs 45%; p = 0.008) and significantly greater LV end-diastolic (LVEDVI) and end-systolic (LVESVI) volume index compared to subject without MVO (n = 136). The frequency of patients with MVO was compared against the frequency of patients without MVO at each 1-h and 3-h period over a 24-h cycle. A clear peak in patients with MVO (MVO + / MVO -) was seen at the 0700 h interval where 26 out of 27 patients had MVO (p = 0.0038) although MVO mass was not increased. This observation remained significant at the 06-09 time interval when 3-h segments were analyzed. Through 2021, mortality in patients with MVO was significantly greater compared to patients without MVO (n = 20 vs. 5, p < 0.03). CONCLUSIONS: This analysis reveals for the first time a circadian dependence of the frequency of MVO in the setting of STEMI which could explain in part, the wide variation in MVO seen in STEMI patients with similar ischemic times and infarct size.


Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Microcirculación , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/cirugía , Remodelación Ventricular
20.
Mov Ecol ; 10(1): 30, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-35843990

RESUMEN

BACKGROUND: Bio-logging and animal tracking datasets continuously grow in volume and complexity, documenting animal behaviour and ecology in unprecedented extent and detail, but greatly increasing the challenge of extracting knowledge from the data obtained. A large variety of analysis methods are being developed, many of which in effect are inaccessible to potential users, because they remain unpublished, depend on proprietary software or require significant coding skills. RESULTS: We developed MoveApps, an open analysis platform for animal tracking data, to make sophisticated analytical tools accessible to a global community of movement ecologists and wildlife managers. As part of the Movebank ecosystem, MoveApps allows users to design and share workflows composed of analysis modules (Apps) that access and analyse tracking data. Users browse Apps, build workflows, customise parameters, execute analyses and access results through an intuitive web-based interface. Apps, coded in R or other programming languages, have been developed by the MoveApps team and can be contributed by anyone developing analysis code. They become available to all user of the platform. To allow long-term and cross-system reproducibility, Apps have public source code and are compiled and run in Docker containers that form the basis of a serverless cloud computing system. To support reproducible science and help contributors document and benefit from their efforts, workflows of Apps can be shared, published and archived with DOIs in the Movebank Data Repository. The platform was beta launched in spring 2021 and currently contains 49 Apps that are used by 316 registered users. We illustrate its use through two workflows that (1) provide a daily report on active tag deployments and (2) segment and map migratory movements. CONCLUSIONS: The MoveApps platform is meant to empower the community to supply, exchange and use analysis code in an intuitive environment that allows fast and traceable results and feedback. By bringing together analytical experts developing movement analysis methods and code with those in need of tools to explore, answer questions and inform decisions based on data they collect, we intend to increase the pace of knowledge generation and integration to match the huge growth rate in bio-logging data acquisition.

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