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1.
Toxicol Ind Health ; : 7482337241253996, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743488

RESUMEN

Hand-arm vibration is a common occupational exposure that causes neurological impairment, myalgia, and vibration-induced Raynaud's phenomena or vibration white fingers (VWF). The pathological mechanism is largely unknown, though several mechanisms have been proposed, involving both immunological vascular damage and defective neural responses. The aim of this study was to test whether the substances interleukin-33 (IL-33), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), endothelin-1 (ET-1), C-C motif chemokine ligand 20 (CCL20), calcitonin, and thromboxane (TXA2) changed before and after occupational hand-arm vibration exposure. 38 full-time shift workers exposed to hand-arm vibration were recruited. All the participants underwent medical examinations regarding symptoms of Raynaud's phenomena. In 29 of the participants, the concentration of IL-33, MDC, IL-10, ET-1, CCL20, calcitonin, and TXA2 was measured before and after a workday. There was a significant increase in ET-1 and calcitonin concentration and a decrease in the CCL20 concentration after the work shift in all participants. In the group suffering from VWF, but not in the non-VWF group, MDC was statistically significantly lower before the work shift (p = .023). The VWF group also showed a significant increase in MDC after the work shift. Exposure to occupational hand-arm vibration is associated with changes in ET-1, calcitonin, and MDC concentration in subjects suffering from vibration white fingers, suggesting a role of these biomarkers in the pathophysiology of this condition.

2.
Toxicol Ind Health ; 39(6): 291-297, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37114914

RESUMEN

Vibration exposure from handheld tools can affect the hands with neurological symptoms and vibration-induced Raynaud's phenomenon (VRP). The underlying pathophysiological mechanisms are not fully known, however, changes in the composition of blood parameters may contribute to VRP with an increase in blood viscosity and inflammatory response. The aim of this study was to examine the effect on blood parameters in capillary blood from fingers that had been exposed to a vibrating hand-held tool. This study involved nine healthy participants who had been exposed to vibration and an unexposed control group of six participants. Capillary blood samples were collected before and after vibration exposure for the exposed group, and repeated samples also from the control group. The exposed groups were exposed to vibration for a 15-min period or until they reached a 5.0 m/s2 vibration dose. Analysis of blood status and differential counting of leucocytes was performed on the capillary blood samples. The results of the blood samples showed an increase in mean value for erythrocyte volume fraction (EVF), hemoglobin, red blood cell count, white blood cell count and neutrophils, as well as a decrease of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration. The increase of EVF and neutrophils was statistically significant for samples taken from the index finger but not the little finger. Even though the study was small it showed that an acute vibration exposure to the hands might increase EVF and neutrophilic granulocytes levels in the capillary blood taken from index fingers.


Asunto(s)
Enfermedades Profesionales , Enfermedad de Raynaud , Humanos , Vibración , Dedos/irrigación sanguínea , Eritrocitos , Enfermedad de Raynaud/diagnóstico , Leucocitos
3.
Infect Dis (Lond) ; 55(6): 396-404, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37021765

RESUMEN

BACKGROUND: Measurements of pleural fluid biomarkers for rapid identification of complicated parapneumonic effusion (CPPE) are crucial for optimal management. Previous studies for biomarker evaluation were however based on pleura culture, not modern DNA technique. Lactate has not been thoroughly studied earlier as a potential biomarker in this regard. OBJECTIVES: To evaluate whether the routine biomarkers pH, glucose, lactate dehydrogenase (LDH) measured in pleural fluid in a microbiological well characterised cohort could differentiate simple parapneumonic effusion (SPPE) from CPPE and if pleural fluid lactate could be of additional use in this discrimination. METHODS: Pleural fluid prospectively collected from adult patients (n = 112) with PPE admitted to the Departments of Infectious Diseases (DIDs) at four Stockholm County hospitals were characterised microbiologically with bacterial culture and 16S rDNA sequencing, and biochemically with pH, glucose, LDH and lactate. RESULTS: Forty and seventy two patients were categorised as SPPE/CPPE. The median values between SPPE/CPPE differed significantly for all biomarkers with varying overlap. Receiver operating characteristics (ROC) curves showed the area under the curve (AUC) for pH 0.905 (CI 0.847-0.963), glucose 0.861 (CI 0.79-0.932), LDH 0.917 (CI 0.860-0.974) and lactate 0.927 (CI 0.877-0.977), corresponding to best cut-off levels and sensitivity/specificity for pH of 7.255, 0.819/0.9, glucose 5.35 mmol/L, 0.847/0.775, LDH 9.8 µcat/L, 0.905/0.825 and lactate 4.9 mmol/L, 0.875/0.85. CONCLUSIONS: To distinguish between SPPE/CPPE, pH and LDH performed well, but optimal cut-off values differed from earlier established recommendations. Pleura lactate had the largest AUC of the investigated biomarkers and may be used in the analyses of PPE-staging.


Asunto(s)
Ácido Láctico , Derrame Pleural , Adulto , Humanos , Diagnóstico Diferencial , Biomarcadores/análisis , L-Lactato Deshidrogenasa/análisis , Glucosa
4.
Nat Commun ; 14(1): 2164, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-37061513

RESUMEN

Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.


Asunto(s)
COVID-19 , Linfocitos T Colaboradores-Inductores , Humanos , Células T Auxiliares Foliculares , SARS-CoV-2 , Células Plasmáticas
5.
Elife ; 122023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36752598

RESUMEN

During respiratory viral infections, the precise roles of monocytes and dendritic cells (DCs) in the nasopharynx in limiting infection and influencing disease severity are incompletely described. We studied circulating and nasopharyngeal monocytes and DCs in healthy controls (HCs) and in patients with mild to moderate infections (primarily influenza A virus [IAV]). As compared to HCs, patients with acute IAV infection displayed reduced DC but increased intermediate monocytes frequencies in blood, and an accumulation of most monocyte and DC subsets in the nasopharynx. IAV patients had more mature monocytes and DCs in the nasopharynx, and higher levels of TNFα, IL-6, and IFNα in plasma and the nasopharynx than HCs. In blood, monocytes were the most frequent cellular source of TNFα during IAV infection and remained responsive to additional stimulation with TLR7/8L. Immune responses in older patients skewed towards increased monocyte frequencies rather than DCs, suggesting a contributory role for monocytes in disease severity. In patients with other respiratory virus infections, we observed changes in monocyte and DC frequencies in the nasopharynx distinct from IAV patients, while differences in blood were more similar across infection groups. Using SomaScan, a high-throughput aptamer-based assay to study proteomic changes between patients and HCs, we found differential expression of innate immunity-related proteins in plasma and nasopharyngeal secretions of IAV and SARS-CoV-2 patients. Together, our findings demonstrate tissue-specific and pathogen-specific patterns of monocyte and DC function during human respiratory viral infections and highlight the importance of comparative investigations in blood and the nasopharynx.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Humanos , Anciano , Monocitos , Factor de Necrosis Tumoral alfa/metabolismo , Proteómica , COVID-19/metabolismo , SARS-CoV-2 , Células Dendríticas
6.
Neurotoxicol Teratol ; 96: 107150, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36584763

RESUMEN

Perfluorinated compounds (PFCs) and polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent environmental compounds, present in humans and at higher levels in infants/children than in adults. This study shows that co-exposure to pentadecafluorooctanoic acid (PFOA) and 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) can significantly exacerbate developmental neurobehavioural defects. Neonatal male NMRI mice, 3 and 10 days old, were exposed perorally to PBDE 209 (1.4 or 8.0 µmol/kg bw), PFOA (1.4 or 14 µmol/kg bw), co-exposed to PBDE 209 and PFOA (at the given doses), or a vehicle (20% fat emulsion) and observed for spontaneous behaviour in a novel home environment when 2 and 4 months old. The behavioural defects observed included hyperactivity and reduced habituation indicating cognitive defects. This interaction appears most likely dependent on the presence of PBDE 209 and/or its metabolites together with PFOA, during a defined critical period of neonatal brain development, corresponding to the perinatal and newborn period in humans.


Asunto(s)
Retardadores de Llama , Bifenilos Polibrominados , Humanos , Animales , Ratones , Embarazo , Femenino , Niño , Masculino , Lactante , Éteres Difenilos Halogenados/toxicidad , Animales Recién Nacidos , Encéfalo
7.
Crit Care Med ; 50(5): 825-836, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35148524

RESUMEN

OBJECTIVES: Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic. DESIGN: Retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5-18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26-37) for COVID-19 and 34 (95% CI, 32-36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29-0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15-1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14-2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI. CONCLUSIONS: COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.


Asunto(s)
COVID-19 , Neumonía Asociada al Ventilador , Infecciones del Sistema Respiratorio , Infecciones Estafilocócicas , COVID-19/epidemiología , COVID-19/terapia , Humanos , Pandemias , Neumonía Asociada al Ventilador/epidemiología , Sistema Respiratorio , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Infecciones Estafilocócicas/epidemiología , Ventiladores Mecánicos
8.
JACC Basic Transl Sci ; 7(3): 193-204, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35194565

RESUMEN

Current knowledge regarding mechanisms underlying cardiovascular complications in patients with COVID-19 is limited and urgently needed. We shed light on a previously unrecognized mechanism and unravel a key role of red blood cells, driving vascular dysfunction in patients with COVID-19 infection. We establish the presence of profound and persistent endothelial dysfunction in vivo in patients with COVID-19. Mechanistically, we show that targeting reactive oxygen species or arginase 1 improves vascular dysfunction mediated by red blood cells. These translational observations hold promise that restoring the redox balance in red blood cells might alleviate the clinical complications of COVID-19-associated vascular dysfunction.

9.
BMC Infect Dis ; 22(1): 108, 2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35100984

RESUMEN

BACKGROUND: A mismatch between a widespread use of broad-spectrum antibiotic agents and a low prevalence of reported bacterial co-infections in patients with SARS-CoV-2 infections has been observed. Herein, we sought to characterize and compare bacterial co-infections at admission in hospitalized patients with SARS-CoV-2, influenza or respiratory syncytial virus (RSV) positive community-acquired pneumonia (CAP). METHODS: A retrospective cohort study of bacterial co-infections at admission in SARS-CoV-2, influenza or RSV-positive adult patients with CAP admitted to Karolinska University Hospital in Stockholm, Sweden, from year 2011 to 2020. The prevalence of bacterial co-infections was investigated and compared between the three virus groups. In each virus group, length of stay, ICU-admission and 30-day mortality was compared in patients with and without bacterial co-infection, adjusting for age, sex and co-morbidities. In the SARS-CoV-2 group, risk factors for bacterial co-infection, were assessed using logistic regression models and creation of two scoring systems based on disease severity, age, co-morbidities and inflammatory markers with assessment of concordance statistics. RESULTS: Compared to influenza and RSV, the bacterial co-infection testing frequency in SARS-CoV-2 was lower for all included test modalities. Four percent [46/1243 (95% CI 3-5)] of all SARS-CoV-2 patients had a bacterial co-infection at admission, whereas the proportion was 27% [209/775 (95% CI 24-30)] and 29% [69/242 (95% CI 23-35)] in influenza and RSV, respectively. S. pneumoniae and S. aureus constituted the most common bacterial findings for all three virus groups. Comparing SARS-CoV-2 positive patients with and without bacterial co-infection at admission, a relevant association could not be demonstrated nor excluded with regards to risk of ICU-admission (aHR 1.53, 95% CI 0.87-2.69) or 30-day mortality (aHR 1.28, 95% CI 0.66-2.46) in adjusted analyses. Bacterial co-infection was associated with increased inflammatory markers, but the diagnostic accuracy was not substantially different in a scoring system based on disease severity, age, co-morbidities and inflammatory parameters [C statistic 0.66 (95% CI 0.59-0.74)], compared to using disease severity, age and co-morbidities only [C statistic 0.63 (95% CI 0.56-0.70)]. CONCLUSIONS: The prevalence of bacterial co-infections was significantly lower in patients with community-acquired SARS-CoV-2 positive pneumonia as compared to influenza and RSV positive pneumonia.


Asunto(s)
COVID-19 , Coinfección , Orthomyxoviridae , Neumonía Viral , Virus Sincitial Respiratorio Humano , Adulto , Coinfección/epidemiología , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Staphylococcus aureus
10.
Sci Rep ; 11(1): 22144, 2021 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-34772983

RESUMEN

Two photoactive iron N-heterocyclic carbene complexes [Formula: see text] and [Formula: see text], where btz is 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2'-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic structure properties and ligand-field interactions, as well as information about the resonantly photo-oxidised final states. Comparing measurements of the Fe centre and the surrounding ligands demonstrate strong mixing of the Fe [Formula: see text] levels with occupied ligand [Formula: see text] orbitals but weak mixing with the corresponding unoccupied ligand orbitals. This highlights the importance of [Formula: see text]-accepting and -donating considerations in ligand design strategies for photofunctional iron carbene complexes. Spin-propensity is also observed as a final-state effect in the RPES measurements of the open-shell [Formula: see text] complex. Vibronic coupling is evident in both complexes, where the energy dispersion hints at a vibrationally hot final state. The results demonstrate the significant impact of the iron oxidation state on the frontier electronic structure and highlights the differences between the emerging class of [Formula: see text] photosensitizers from those of more traditional [Formula: see text] complexes.

11.
JCI Insight ; 6(22)2021 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-34665783

RESUMEN

Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19 , Inmunización Secundaria , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Pulmón/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Humoral/efectos de los fármacos , Estudios Longitudinales , Masculino , Persona de Mediana Edad
12.
Rev Sci Instrum ; 92(4): 044101, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-34243480

RESUMEN

An experimental approach is described in which well-defined perturbations of the gas feed into an Ambient Pressure X-ray Photoelectron Spectroscopy (APXPS) cell are fully synchronized with the time-resolved x-ray photoelectron spectroscopy data acquisition. These experiments unlock new possibilities for investigating the properties of materials and chemical reactions mediated by their surfaces, such as those in heterogeneous catalysis, surface science, and coating/deposition applications. Implementation of this approach, which is termed perturbation-enhanced APXPS, at the SPECIES beamline of MAX IV Laboratory is discussed along with several experimental examples including individual pulses of N2 gas over a Au foil, a multi-pulse titration of oxygen vacancies in a pre-reduced TiO2 single crystal with O2 gas, and a sequence of alternating precursor pulses for atomic layer deposition of TiO2 on a silicon wafer substrate.

13.
Crit Care ; 25(1): 209, 2021 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-34127046

RESUMEN

BACKGROUND: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. METHODS: We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO2 ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. RESULTS: Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8-8.4] in the control group compared with 9.0 h per day [IQR 4.4-10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference - 18% (95% CI - 2 to - 33%); P = 0.032). There were no other differences in secondary outcomes between groups. CONCLUSIONS: The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care. TRIAL REGISTRATION: ISRCTN54917435. Registered 15 June 2020 ( https://doi.org/10.1186/ISRCTN54917435 ).


Asunto(s)
COVID-19/terapia , Terapia por Inhalación de Oxígeno/métodos , Posicionamiento del Paciente/métodos , Posición Prona , Insuficiencia Respiratoria/prevención & control , Adulto , COVID-19/complicaciones , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal/efectos adversos , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/etiología , Vigilia
14.
BMC Infect Dis ; 21(1): 494, 2021 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34044758

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic. The understanding of the transmission and the duration of viral shedding in SARS-CoV-2 infection is still limited. OBJECTIVES: To assess the timeframe and potential risk of SARS-CoV-2 transmission from hospitalized COVID-19 patients in relation to antibody response. METHOD: We performed a cross-sectional study of 36 COVID-19 patients hospitalized at Karolinska University Hospital. Patients with more than 8 days of symptom duration were sampled from airways, for PCR analysis of SARS-CoV-2 RNA and in vitro culture of replicating virus. Serum SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies titers were assessed by immunofluorescence assay (IFA) and microneutralization assay. RESULTS: SARS-CoV-2 RNA was detected in airway samples in 23 patients (symptom duration median 15 days, range 9-53 days), whereas 13 patients were SARS-CoV-2 RNA negative (symptom duration median 21 days, range 10-37 days). Replicating virus was detected in samples from 4 patients at 9-16 days. All but two patients had detectable levels of SARS-CoV-2-specific IgG in serum, and SARS-CoV-2 neutralizing antibodies were detected in 33 out of 36 patients. Total SARS-CoV-2-specific IgG titers and neutralizing antibody titers were positively correlated. High levels of both total IgG and neutralizing antibody titers were observed in patients sampled later after symptom onset and in patients where replicating virus could not be detected. CONCLUSIONS: Our data suggest that the presence of SARS-Cov-2 specific antibodies in serum may indicate a lower risk of shedding infectious SARS-CoV-2 by hospitalized COVID-19 patients.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/virología , SARS-CoV-2/inmunología , Esparcimiento de Virus , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , COVID-19/sangre , COVID-19/inmunología , Prueba Serológica para COVID-19/métodos , Estudios Transversales , Femenino , Hospitalización , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Pandemias , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/análisis , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Esputo/virología
15.
J Synchrotron Radiat ; 28(Pt 2): 588-601, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33650571

RESUMEN

The SPECIES beamline has been transferred to the new 1.5 GeV storage ring at the MAX IV Laboratory. Several improvements have been made to the beamline and its endstations during the transfer. Together the Ambient Pressure X-ray Photoelectron Spectroscopy and Resonant Inelastic X-ray Scattering endstations are capable of conducting photoelectron spectroscopy in elevated pressure regimes with enhanced time-resolution and flux and X-ray scattering experiments with improved resolution and flux. Both endstations offer a unique capability for experiments at low photon energies in the vacuum ultraviolet and soft X-ray range. In this paper, the upgrades on the endstations and current performance of the beamline are reported.

16.
J Clin Invest ; 131(6)2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33492309

RESUMEN

The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.


Asunto(s)
COVID-19/inmunología , Células Supresoras de Origen Mieloide/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Arginasa/sangre , COVID-19/sangre , COVID-19/patología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Gripe Humana/sangre , Gripe Humana/inmunología , Gripe Humana/patología , Interferón gamma/sangre , Interleucina-6/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Células Supresoras de Origen Mieloide/patología , Pandemias , Sistema Respiratorio/inmunología , Sistema Respiratorio/patología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Linfocitos T/inmunología , Linfocitos T/patología , Adulto Joven
17.
J Phys Condens Matter ; 32(41): 413003, 2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-32438360

RESUMEN

In this topical review we catagorise all ambient pressure x-ray photoelectron spectroscopy publications that have appeared between the 1970s and the end of 2018 according to their scientific field. We find that catalysis, surface science and materials science are predominant, while, for example, electrocatalysis and thin film growth are emerging. All catalysis publications that we could identify are cited, and selected case stories with increasing complexity in terms of surface structure or chemical reaction are discussed. For thin film growth we discuss recent examples from chemical vapour deposition and atomic layer deposition. Finally, we also discuss current frontiers of ambient pressure x-ray photoelectron spectroscopy research, indicating some directions of future development of the field.

18.
J Phys Chem A ; 124(8): 1603-1609, 2020 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-32011141

RESUMEN

We present the first experimental study of the frontier orbitals in an ultrathin film of the novel hexa-carbene photosensitizer [Fe(btz)3]3+, where btz is 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene). Resonant photoelectron spectroscopy (RPES) was used to probe the electronic structure of films where the molecular and oxidative integrities had been confirmed with optical and X-ray spectroscopies. In combination with density functional theory calculations, RPES measurements provided direct and site-selective information about localization and interactions of occupied and unoccupied molecular orbitals. Fe 2p, N 1s, and C 1s measurements selectively probed the metal, carbene, and side-group contributions revealing strong metal-ligand orbital mixing of the frontier orbitals. This helps explain the remarkable photophysical properties of iron-carbenes in terms of unconventional electronic structure properties and favorable metal-ligand bonding interactions-important for the continued development of these type of complexes toward light-harvesting and light-emitting applications.

19.
Materials (Basel) ; 12(22)2019 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-31718101

RESUMEN

An in-depth understanding of the reaction mechanism is required for the further development of Mo-based catalysts for biobased feedstocks. However, fundamental studies of industrial catalysts are challenging, and simplified systems are often used without direct comparison to their industrial counterparts. Here, we report on size-selected bimetallic NiMo nanoparticles as a candidate for a model catalyst that is directly compared to the industrial system to evaluate their industrial relevance. Both the nanoparticles and industrial supported NiMo catalysts were characterized using surface- and bulk-sensitive techniques. We found that the active Ni and Mo metals in the industrial catalyst are well dispersed and well mixed on the support, and that the interaction between Ni and Mo promotes the reduction of the Mo oxide. We successfully produced 25 nm NiMo alloyed nanoparticles with a narrow size distribution. Characterization of the nanoparticles showed that they have a metallic core with a native oxide shell with a high potential for use as a model system for fundamental studies of hydrotreating catalysts for biobased feedstocks.

20.
Front Immunol ; 10: 1116, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31156653

RESUMEN

NK cells in the human lung respond to influenza A virus- (IAV-) infected target cells. However, the detailed functional capacity of human lung and peripheral blood NK cells remains to be determined in IAV and other respiratory viral infections. Here, we investigated the effects of IAV infection on human lung and peripheral blood NK cells in vitro and ex vivo following clinical infection. IAV infection of lung- and peripheral blood-derived mononuclear cells in vitro induced NK cell hyperresponsiveness to K562 target cells, including increased degranulation and cytokine production particularly in the CD56brightCD16- subset of NK cells. Furthermore, lung CD16- NK cells showed increased IAV-mediated but target cell-independent activation compared to CD16+ lung NK cells or total NK cells in peripheral blood. IAV infection rendered peripheral blood NK cells responsive toward the normally NK cell-resistant lung epithelial cell line A549, indicating that NK cell activation during IAV infection could contribute to killing of surrounding non-infected epithelial cells. In vivo, peripheral blood CD56dimCD16+ and CD56brightCD16- NK cells were primed during acute IAV infection, and a small subset of CD16-CD49a+CXCR3+ NK cells could be identified, with CD49a and CXCR3 potentially promoting homing to and tissue-retention in the lung during acute infection. Together, we show that IAV respiratory viral infections prime otherwise hyporesponsive lung NK cells, indicating that both CD16+ and CD16- NK cells including CD16-CD49a+ tissue-resident NK cells could contribute to host immunity but possibly also tissue damage in clinical IAV infection.


Asunto(s)
Virus de la Influenza A/fisiología , Gripe Humana/inmunología , Pulmón/fisiología , Presentación de Antígeno , Circulación Sanguínea , Hiperreactividad Bronquial/metabolismo , Citotoxicidad Inmunológica , Humanos , Células K562 , Células Asesinas Naturales/inmunología , Activación de Linfocitos
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