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1.
Nat Immunol ; 23(5): 781-790, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35383307

RESUMEN

Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.


Asunto(s)
COVID-19 , SARS-CoV-2 , Linfocitos T CD8-positivos , Humanos , Fenotipo , Receptores de Antígenos de Linfocitos T/genética , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas Sintéticas , Vacunas de ARNm
2.
Nature ; 628(8006): 162-170, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38538791

RESUMEN

Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies1,2. Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena3. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune responses, while limiting the production of myeloid cells, which can be pro-inflammatory4. Ageing is associated with increased proportions of my-HSCs, resulting in decreased lymphopoiesis and increased myelopoiesis3,5,6. Transfer of bal-HSCs results in abundant lymphoid and myeloid cells, a stable phenotype that is retained after secondary transfer; my-HSCs also retain their patterns of production after secondary transfer5. The origin and potential interconversion of these two subsets is still unclear. If they are separate subsets postnatally, it might be possible to reverse the ageing phenotype by eliminating my-HSCs in aged mice. Here we demonstrate that antibody-mediated depletion of my-HSCs in aged mice restores characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.


Asunto(s)
Inmunidad Adaptativa , Envejecimiento , Linaje de la Célula , Células Madre Hematopoyéticas , Linfocitos , Células Mieloides , Rejuvenecimiento , Animales , Femenino , Masculino , Ratones , Inmunidad Adaptativa/inmunología , Envejecimiento/inmunología , Linfocitos B/citología , Linfocitos B/inmunología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Inflamación/inmunología , Inflamación/patología , Linfocitos/citología , Linfocitos/inmunología , Linfopoyesis , Células Mieloides/citología , Células Mieloides/inmunología , Mielopoyesis , Fenotipo , Linfocitos T/citología , Linfocitos T/inmunología , Virus/inmunología
3.
Nature ; 625(7994): 264-269, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38093009

RESUMEN

Spin nematic is a magnetic analogue of classical liquid crystals, a fourth state of matter exhibiting characteristics of both liquid and solid1,2. Particularly intriguing is a valence-bond spin nematic3-5, in which spins are quantum entangled to form a multipolar order without breaking time-reversal symmetry, but its unambiguous experimental realization remains elusive. Here we establish a spin nematic phase in the square-lattice iridate Sr2IrO4, which approximately realizes a pseudospin one-half Heisenberg antiferromagnet in the strong spin-orbit coupling limit6-9. Upon cooling, the transition into the spin nematic phase at TC ≈ 263 K is marked by a divergence in the static spin quadrupole susceptibility extracted from our Raman spectra and concomitant emergence of a collective mode associated with the spontaneous breaking of rotational symmetries. The quadrupolar order persists in the antiferromagnetic phase below TN ≈ 230 K and becomes directly observable through its interference with the antiferromagnetic order in resonant X-ray diffraction, which allows us to uniquely determine its spatial structure. Further, we find using resonant inelastic X-ray scattering a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state10,11. Taken together, our results reveal a quantum order underlying the Néel antiferromagnet that is widely believed to be intimately connected to the mechanism of high-temperature superconductivity12,13.

4.
Nature ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862026

RESUMEN

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

5.
Nature ; 609(7928): 734-740, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35697059

RESUMEN

Volcanoes can produce tsunamis by means of earthquakes, caldera and flank collapses, pyroclastic flows or underwater explosions1-4. These mechanisms rarely displace enough water to trigger transoceanic tsunamis. Violent volcanic explosions, however, can cause global tsunamis1,5 by triggering acoustic-gravity waves6-8 that excite the atmosphere-ocean interface. The colossal eruption of the Hunga Tonga-Hunga Ha'apai volcano and ensuing tsunami is the first global volcano-triggered tsunami recorded by modern, worldwide dense instrumentation, thus providing a unique opportunity to investigate the role of air-water-coupling processes in tsunami generation and propagation. Here we use sea-level, atmospheric and satellite data from across the globe, along with numerical and analytical models, to demonstrate that this tsunami was driven by a constantly moving source in which the acoustic-gravity waves radiating from the eruption excite the ocean and transfer energy into it by means of resonance. A direct correlation between the tsunami and the acoustic-gravity waves' arrival times confirms that these phenomena are closely linked. Our models also show that the unusually fast travel times and long duration of the tsunami, as well as its global reach, are consistent with an air-water-coupled source. This coupling mechanism has clear hazard implications, as it leads to higher waves along land masses that rise abruptly from long stretches of deep ocean waters.

6.
Nature ; 609(7926): 269-275, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36071190

RESUMEN

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

7.
Nat Chem Biol ; 20(7): 894-905, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38658655

RESUMEN

Calcium ions serve as key intracellular signals. Local, transient increases in calcium concentrations can activate calcium sensor proteins that in turn trigger downstream effectors. In neurons, calcium transients play a central role in regulating neurotransmitter release and synaptic plasticity. However, it is challenging to capture the molecular events associated with these localized and ephemeral calcium signals. Here we present an engineered biotin ligase that generates permanent molecular traces in a calcium-dependent manner. The enzyme, calcium-dependent BioID (Cal-ID), biotinylates nearby proteins within minutes in response to elevated local calcium levels. The biotinylated proteins can be identified via mass spectrometry and visualized using microscopy. In neurons, Cal-ID labeling is triggered by neuronal activity, leading to prominent protein biotinylation that enables transcription-independent activity labeling in the brain. In summary, Cal-ID produces a biochemical record of calcium signals and neuronal activity with high spatial resolution and molecular specificity.


Asunto(s)
Biotinilación , Señalización del Calcio , Calcio , Neuronas , Calcio/metabolismo , Neuronas/metabolismo , Animales , Ligasas de Carbono-Nitrógeno/metabolismo , Ligasas de Carbono-Nitrógeno/química , Humanos , Ratones , Células HEK293 , Proteínas Represoras , Proteínas de Escherichia coli
8.
Nature ; 569(7757): 546-550, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31118523

RESUMEN

The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.

9.
Proc Natl Acad Sci U S A ; 119(32): e2203760119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35867811

RESUMEN

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.1.529 (omicron) lineages. Our data reveal that relative to ancestral isolates, SARS-CoV-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.


Asunto(s)
Antivirales , COVID-19 , Interferones , SARS-CoV-2 , Anticuerpos Neutralizantes , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/transmisión , Humanos , Interferones/farmacología , Interferones/uso terapéutico , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genética
10.
Proteins ; 92(1): 52-59, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37596815

RESUMEN

The core metabolic reactions of life drive electrons through a class of redox protein enzymes, the oxidoreductases. The energetics of electron flow is determined by the redox potentials of organic and inorganic cofactors as tuned by the protein environment. Understanding how protein structure affects oxidation-reduction energetics is crucial for studying metabolism, creating bioelectronic systems, and tracing the history of biological energy utilization on Earth. We constructed ProtReDox (https://protein-redox-potential.web.app), a manually curated database of experimentally determined redox potentials. With over 500 measurements, we can begin to identify how proteins modulate oxidation-reduction energetics across the tree of life. By mapping redox potentials onto networks of oxidoreductase fold evolution, we can infer the evolution of electron transfer energetics over deep time. ProtReDox is designed to include user-contributed submissions with the intention of making it a valuable resource for researchers in this field.


Asunto(s)
Oxidorreductasas , Oxidorreductasas/química , Oxidación-Reducción , Transporte de Electrón
11.
Stroke ; 55(3): 670-677, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38288608

RESUMEN

BACKGROUND: Cervical artery dissection (CeAD) represents up to 15% to 25% of ischemic strokes in people under the age of 50 years. Noninvasive vessel imaging is increasingly used in clinical practice, but the impact on the frequency of detection of CeAD is unknown. In 2006, the yearly incidence rate of CeAD was estimated at 2.6 per 100 000 person-years, but the current incidence is unknown. METHODS: In this population-based retrospective observational cohort study, we utilized the resources of the Rochester Epidemiology Project to ascertain all adult residents of Olmsted County, MN, diagnosed with internal carotid artery dissection and common carotid artery dissection or vertebral artery dissection from 2002 to 2020. Patients with only intracranial involvement or CeAD following major trauma were excluded. Age-adjusted sex-specific and age- and sex-adjusted incidence rates were estimated using the US White 2010 decennial census, with rates expressed per 100 000 person-years. We assessed longitudinal trends by dividing the data into 5-year time intervals, with the last being a 4-year interval. RESULTS: We identified 123 patients with a diagnosis of CeAD. There were 63 patients with internal carotid artery dissection, 54 with vertebral artery dissection, 2 with concurrent internal carotid artery dissection and vertebral artery dissection, and 4 with common carotid artery dissection. There were 63 (51.2%) female patients and 60 (48.8%) male patients. The average age at diagnosis was 50.2 years (SD, 15.1 [95% CI, 20.1-90.5] years). The incidence rate of spontaneous CeAD encompassing all locations was 4.69 per 100 000 person-years (2.43 for internal carotid artery dissection and 2.01 for vertebral artery dissection). The incidence rate increased from 2.30 per 100 000 person-years from 2002 to 2006 to 8.93 per 100 000 person-years from 2017 to 2020 (P<0.0001). The incidence rate for female patients rose from 0.81 per 100 000 person-years from 2002 to 2006 to 10.17 per 100 000 person-years from 2017 to 2020. CONCLUSIONS: The incidence rate of spontaneous CeAD increased nearly 4-fold over a 19-year period from 2002 to 2020. The incidence rate in women rose over 12-fold. The increase in incidence rates likely reflects the increased use of noninvasive vascular imaging.


Asunto(s)
Disección de la Arteria Carótida Interna , Accidente Cerebrovascular , Disección de la Arteria Vertebral , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arterias , Disección de la Arteria Carótida Interna/diagnóstico por imagen , Disección de la Arteria Carótida Interna/epidemiología , Disección de la Arteria Carótida Interna/etiología , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Disección de la Arteria Vertebral/diagnóstico por imagen , Disección de la Arteria Vertebral/epidemiología , Disección de la Arteria Vertebral/complicaciones , Adulto Joven , Anciano , Anciano de 80 o más Años
12.
Mol Hum Reprod ; 30(3)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38290796

RESUMEN

Uterine leiomyoma (LM), also known as uterine fibroids, are common gynecological tumors and can reach a prevalence of 70% among women by the age of 50 years. Notably, the LM burden is much higher in Black women with earlier onset, a greater tumor number, size, and severity compared to White women. Published knowledge shows that there are genetic, environmental, and lifestyle-based risk factors associated with racial disparity for LM. Significant strides have been made on genomic, epigenomic, and transcriptomic data levels in Black and White women to elucidate the underlying pathomolecular reasons of racial disparity in LM development. However, racial disparity of LM remains a major area of concern in gynecological research. This review highlights risk factors of LM and their role in different races. Furthermore, we discuss the genetics and uterine myometrial microenvironment in LM development. Comparative findings revealed that a major racial difference in the disease is linked to myometrial oxidative burden and altered ROS pathways which is relevant to the oxidized guanine in genomic DNA and MED12 mutations that drive the LM genesis. Considering the burden and morbidity of LM, we anticipate that this review on genetic risk and myometrial microenvironment will strengthen understanding and propel the growth of research to address the racial disparity of LM burden.


Asunto(s)
Leiomioma , Neoplasias Uterinas , Femenino , Humanos , Persona de Mediana Edad , Negro o Afroamericano , Perfilación de la Expresión Génica , Leiomioma/genética , Leiomioma/metabolismo , Miometrio/metabolismo , Microambiente Tumoral , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Útero/metabolismo , Blanco
13.
PLoS Pathog ; 18(4): e1010155, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35404959

RESUMEN

Macaques are a commonly used model for studying immunity to human viruses, including for studies of SARS-CoV-2 infection and vaccination. However, it is unknown whether macaque antibody responses resemble the response in humans. To answer this question, we employed a phage-based deep mutational scanning approach (Phage-DMS) to compare which linear epitopes are targeted on the SARS-CoV-2 Spike protein in convalescent humans, convalescent (re-infected) rhesus macaques, mRNA-vaccinated humans, and repRNA-vaccinated pigtail macaques. We also used Phage-DMS to determine antibody escape pathways within each epitope, enabling a granular comparison of antibody binding specificities at the locus level. Overall, we identified some common epitope targets in both macaques and humans, including in the fusion peptide (FP) and stem helix-heptad repeat 2 (SH-H) regions. Differences between groups included a response to epitopes in the N-terminal domain (NTD) and C-terminal domain (CTD) in vaccinated humans but not vaccinated macaques, as well as recognition of a CTD epitope and epitopes flanking the FP in convalescent macaques but not convalescent humans. There was also considerable variability in the escape pathways among individuals within each group. Sera from convalescent macaques showed the least variability in escape overall and converged on a common response with vaccinated humans in the SH-H epitope region, suggesting highly similar antibodies were elicited. Collectively, these findings suggest that the antibody response to SARS-CoV-2 in macaques shares many features with humans, but with substantial differences in the recognition of certain epitopes and considerable individual variability in antibody escape profiles, suggesting a diverse repertoire of antibodies that can respond to major epitopes in both humans and macaques. Differences in macaque species and exposure type may also contribute to these findings.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Formación de Anticuerpos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Epítopos , Humanos , Macaca mulatta , Glicoproteína de la Espiga del Coronavirus , Vacunación
14.
Genet Med ; : 101171, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38828701

RESUMEN

PURPOSE: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance due to an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families. METHODS: Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10.000 person years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onwards. Attained-age analyses were performed for sites in which significant increased risks were found. Considering study design, we primarily focused on cancer risk in women. RESULTS: We found significant increased risks of colorectal cancer (CRC; SIR=1.43, 95%CI=1.14-1.76; AER=1.43) and hematological cancers (SIR=1.32; 95%CI=1.02-1.67; AER=0.87). CRC was significantly more frequent from age 45 onwards. CONCLUSION: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well, however, further research is needed to determine who may profit from this additional colorectal surveillance.

15.
Opt Lett ; 49(12): 3348-3351, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875617

RESUMEN

We report on observations of coherent, sustained oscillations in the absorption of continuous-wave light at 388 nm that excites the 6S1/2 → 8P3/2 transition in cesium (Cs) vapor. The oscillation frequency is close to the spacing of hyperfine levels of the 8P3/2 level that are excited simultaneously by the 388 nm field. We observe a threshold behavior of the oscillation amplitude with pump power and suggest that the effect is associated with infrared directional emission due to amplified spontaneous emission (ASE) from the 8P3/2 → 8S1/2 transition that is assisted by retro-reflections from cell windows. The effect may be used to probe a lasing process in an atomic vapor, by checking the temporal properties of the pump field transmitted through the vapor.

16.
Scand J Rheumatol ; 53(4): 248-254, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38686835

RESUMEN

OBJECTIVE: To evaluate the prevalence and rate of a missed diagnosis of sacroiliitis on abdominal computed tomography (CT) in patients with inflammatory bowel disease (IBD). Factors associated with sacroiliitis were also assessed. METHOD: This retrospective study included 210 patients with IBD (mean age 31.1 years) who underwent abdominal CT. Based on a validated abdominal CT scoring tool, bilateral sacroiliac (SI) joints on abdominal CT in the whole study population were retrospectively reviewed. Subsequently, patients were classified into the 'patients with sacroiliitis' group and the 'patients without sacroiliitis' group. Univariate and multivariate regression analyses were used to clarify the factors associated with sacroiliitis. RESULTS: Sacroiliitis was identified in 26 out of 210 patients (12.4%). However, sacroiliitis was recognized on the primary reading in only five of these 26 patients (19.2%) and was missed on the initial report in the remaining 21 patients (80.8%). Among the 21 patients, 20 (95.2%) were finally diagnosed with axial spondyloarthritis (axSpA). There was a higher prevalence of female sex (p = 0.04), upper gastrointestinal involvement (p = 0.04), and back pain (p < 0.01) in patients with sacroiliitis than in those without sacroiliitis. However, on multivariate analysis, back pain was the only factor associated with sacroiliitis (p = 0.01). CONCLUSION: Physicians should carefully evaluate SI joints on abdominal CT in patients with IBD to enable early detection of sacroiliitis, potentially leading to an early diagnosis of axSpA. In addition, if patients with IBD present with back pain, the possibility of sacroiliitis should be considered.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Sacroileítis , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Sacroileítis/diagnóstico por imagen , Sacroileítis/epidemiología , Adulto , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Enfermedades Inflamatorias del Intestino/complicaciones , Prevalencia , Persona de Mediana Edad , Adulto Joven , Diagnóstico Erróneo/estadística & datos numéricos , Articulación Sacroiliaca/diagnóstico por imagen , Espondiloartritis Axial/epidemiología , Espondiloartritis Axial/diagnóstico por imagen
17.
AJR Am J Roentgenol ; : 1-14, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37530400

RESUMEN

Patients with Crohn disease commonly have bowel strictures develop, which exhibit varying degrees of inflammation and fibrosis. Differentiation of the distinct inflammatory and fibrotic components of strictures is key for the optimization of therapeutic management and for the development of antifibrotic drugs. Cross-sectional imaging techniques, including ultrasound, CT, and MRI, allow evaluation of the full thickness of the bowel wall as well as extramural complications and associated mesenteric abnormalities. Although promising data have been reported for a range of novel imaging biomarkers for detection of fibrosis and quantification of the degree of fibrosis, these biomarkers lack sufficient validation and standardization for clinical use. Additional methods, including PET with emerging radiotracers, artificial intelligence, and radiomics, are also under investigation for stricture characterization. In this review, we highlight the clinical relevance of identifying fibrosis in Crohn disease, review the histopathologic aspects of strictures in Crohn disease, summarize the morphologic imaging findings of strictures, and explore contemporary developments in the use of cross-sectional imaging techniques for detecting and characterizing intestinal strictures, with attention given to emerging quantitative biomarkers.

18.
Environ Sci Technol ; 58(16): 7154-7164, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38590004

RESUMEN

Compared to aquatic ecosystem, terrestrial systems have been subjected to fewer investigations on the exposure to halogenated flame retardants (HFRs). Our study utilized peregrine falcon eggs collected from multiple habitats across North America to retrospectively explore both spatial distribution and temporal changes in legacy (e.g., polybrominated diphenyl ethers) and alternative HFRs over a 30 year period (1984-2016). The results reveal intensive HFR exposure in terrestrial ecosystems and chemical-specific spatiotemporal distribution patterns. The correlations between egg levels of the selected HFRs and human population density clearly illustrated a significant urban influence on the exposure of this wildlife species to these HFRs and subsequent maternal transfer to their eggs. Temporal analyses suggest that, unlike aquatic systems, terrestrial ecosystems may undergo continual exposure to consistently high levels of legacy HFRs for a long period of time. Our findings collectively highlight the effectiveness of using peregrine eggs to monitor terrestrial exposure to HFRs and other bioaccumulative chemicals and the need for continuous monitoring of HFRs in terrestrial ecosystems.

19.
J Immunol ; 208(6): 1371-1377, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35236754

RESUMEN

CD47 is an important innate immune checkpoint through its interaction with its inhibitory receptor on macrophages, signal-regulatory protein α (SIRPα). Therapeutic blockade of CD47-SIRPα interactions is a promising immuno-oncology treatment that promotes clearance of cancer cells. However, CD47-SIRPα interactions also maintain homeostatic lymphocyte levels. In this study, we report that the mouse splenic marginal zone B cell population is dependent on intact CD47-SIRPα interactions and blockade of CD47 leads to the loss of these cells. This depletion is accompanied by elevated levels of monocyte-recruiting chemokines CCL2 and CCL7 and infiltration of CCR2+Ly6Chi monocytes into the mouse spleen. In the absence of CCR2 signaling, there is no infiltration and reduced marginal zone B cell depletion. These data suggest that CD47 blockade leads to clearance of splenic marginal zone B cells.


Asunto(s)
Antígeno CD47 , Monocitos , Animales , Antígenos de Diferenciación , Quimiocinas , Ratones , Monocitos/metabolismo , Fagocitosis , Receptores Inmunológicos
20.
Clin Radiol ; 79(1): e182-e188, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37925364

RESUMEN

AIM: To analyse the clinicoradiological characteristics of traumatic inferior vena cava (IVC) injury level on preoperative computed tomography (CT). MATERIALS AND METHODS: This retrospective study evaluated patients from a single trauma centre treated for traumatic IVC injury between January 2014 and January 2021. Data on demographics, mechanism of injury, Injury Severity Score, radiological findings on CT and angiography, IVC injury level in surgical findings, complications, and clinical outcomes were collected. RESULTS: During the 8-year study period, 36 patients presented with traumatic IVC injury: 19 underwent preoperative CT with 17 (89%) blunt and two (11%) penetrating injuries. The most common primary CT sign was contour abnormality (53%, n=10), followed by intraluminal flap and active extravasation (21%, n=4). Among the secondary signs, hepatic laceration (53%, n=10) and retroperitoneal haemorrhage (53%, n=10) were the most common. Frequencies of primary and secondary signs were higher in the infrarenal and suprarenal than in the retrohepatic vena cava injuries. Diagnostic capability of preoperative CT for IVC injury differed according to the IVC level. The detection rate was the highest for an infrarenal vena cava injury at 100% (n=4), followed by that for a suprarenal, suprahepatic, and retrohepatic vena cava injuries at 75% (n=3), 43% (n=3), and 25% (n=1), respectively. CONCLUSION: CT findings of traumatic IVC injuries may vary depending on the mechanism and anatomical site of injury. Familiarity with IVC injury imaging features may help in diagnosis and surgical treatment planning.


Asunto(s)
Traumatismos Abdominales , Lesiones del Sistema Vascular , Humanos , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/lesiones , Estudios Retrospectivos , Centros Traumatológicos , Hígado/diagnóstico por imagen , Lesiones del Sistema Vascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X
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