Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 118
Filtrar
1.
Sci Adv ; 10(23): eadk2693, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838155

RESUMO

T helper 1 (TH1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated TH1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the TH2 lineage: T-bet quantities were inversely correlated with the ability to express the TH2 lineage-specifying transcription factor GATA-3 and TH2 cytokines. Reprogramed TH1 cells acquired graded mixed TH1 + TH2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated TH1 cells was essential to ensure TH1 cell stability. Thus, innate cytokine signals regulate TH1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.


Assuntos
Diferenciação Celular , Linhagem da Célula , Plasticidade Celular , Proteínas com Domínio T , Células Th1 , Células Th2 , Células Th1/imunologia , Células Th1/metabolismo , Proteínas com Domínio T/metabolismo , Proteínas com Domínio T/genética , Animais , Linhagem da Célula/genética , Células Th2/imunologia , Células Th2/metabolismo , Camundongos , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/genética , Interferon gama/metabolismo , Regulação da Expressão Gênica , Citocinas/metabolismo
2.
J Chem Phys ; 160(14)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38591684

RESUMO

This work outlines conditions suitable for the heteroepitaxial growth of Cr2O3(0001) films (1.5-20 nm thick) on a Ru(0001)-terminated substrate. Optimized growth is achieved by sputter deposition of Cr within a 4 mTorr Ar/O2 20% ambient at Ru temperatures ranging from 450 to 600 °C. The Cr2O3 film adopts a 30° rotated honeycomb configuration with respect to the underlying Ru(0001) substrate and exhibits a hexagonal lattice parameter consistent with that for bulk Cr2O3(0001). Heating to 700 °C within the same environment during film preparation leads to Ru oxidation. Exposure to temperatures at or above 400 °C in a vacuum, Ar, or Ar/H2 3% leads to chromia film degradation characterized by increased Ru 3d XPS intensity coupled with concomitant Cr 2p and O 1s peak attenuations when compared to data collected from unannealed films. An ill-defined but hexagonally well-ordered RuxCryOz surface structure is noted after heating the film in this manner. Heating within a wet Ar/H2 3% environment preserves the Cr2O3(0001)/Ru(0001) heterolayer structure to temperatures of at least 950 °C. Heating an Ru-Cr2O3-Ru heterostacked film to 950 °C within this environment is shown by cross-sectional scanning/transmission electron microscopy (S/TEM) to provide clear evidence of retained epitaxial bicrystalline oxide interlayer structure, interlayer immiscibility, and epitaxial registry between the top and bottom Ru layers. Subtle effects marked by O enrichment and O 1s and Cr 2p shifts to increased binding energies are noted by XPS in the near-Ru regions of Cr2O3(0001)/Ru(0001) and Ru(0001)/Cr2O3(0001)/Ru(0001) films after annealing to different temperatures in different sets of environmental conditions.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38626354

RESUMO

RATIONALE: Immune checkpoint inhibitor-related pneumonitis is a serious autoimmune event affecting up to 20% of patients with non-small cell lung cancer, yet the factors underpinning its development in some patients and not others are poorly understood. OBJECTIVES: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. METHODS: The study cohort consisted of non-small cell lung cancer patients who gave blood samples before and during immune checkpoint inhibitor treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with non-small cell lung cancer and patients with melanoma. MEASUREMENTS AND MAIN RESULTS: Across both cohorts, patients who developed pneumonitis had higher pre-treatment levels of immunoglobulin G autoantibodies targeting surfactant protein-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4+ interferon-gamma-positive surfactant protein B-specific T cells, and expanding T cell clonotypes recognizing this protein, accompanied by a pro-inflammatory serum proteomic profile. CONCLUSIONS: Our data suggest that the co-occurrence of surfactant protein-B-specific immunoglobulin G autoantibodies and CD4+ T cells is associated with the development of pneumonitis during ICI therapy. Pre-treatment levels of these antibodies may represent a potential biomarker for elevated risk of developing pneumonitis and on-treatment levels may provide a diagnostic aid. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

4.
Can J Anaesth ; 71(5): 629-639, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514524

RESUMO

PURPOSE: Core body temperature has been extensively investigated as a thereuptic target in care after cardiac arrest. Nevertheless, the integrity of thermoregulation in patients after cardiac arrest has not been well studied. We sought to evaluate whether low spontaneous body temperature after cardiac arrest is associated with increased death and a worse neurologic outcome, and whether patients with low spontaneous body temperature exhibit features suggestive of impaired thermoregulation. METHODS: We conducted a single-centre retrospective cohort study. We included all adult patients who underwent temperature control with hypothermia after cardiac arrest between 1 January 2014 and 30 June 2020. The primary exposure was low spontaneous core body temperature (< 35 °C) at initiation of hypothermia therapy. The primary outcome was in-hospital death and the secondary outcome was poor neurologic outcomes at discharge. RESULTS: Five hundred and ninety-seven adult patients, comprising both in- and out-of-hospital cardiac arrests, were included. Patients with low spontaneous body temperature also had slightly lower average temperature, and more frequent transient but controlled breakthrough fever episodes in the first 24 hr. In the multivariable logistic regression analysis, low spontaneous body temperature was associated with higher odds of in-hospital death (odds ratio, 2.9; 95% confidence interval, 1.9 to 4.2; P < 0.001). CONCLUSION: In this single-centre retrospective cohort study, low spontaneous core body temperature was associated with poor outcomes in patients after cardiac arrest. Patients with low spontaneous body temperature also exhibited features suggestive of impaired thermoregulation. Further research is needed to determine whether body temperature upon presentation reflects the robustness of the patient's underlying physiology and severity of brain insult after a cardiac arrest.


RéSUMé: OBJECTIF: La température corporelle centrale a fait l'objet d'études approfondies en tant que cible thérapeutique dans les soins après un arrêt cardiaque. Néanmoins, l'intégrité de la thermorégulation après un arrêt cardiaque n'a pas été bien étudiée. Nous avons cherché à évaluer si une température corporelle spontanément basse après un arrêt cardiaque était associée à une augmentation de la mortalité et à une issue neurologique plus grave, et si les individus ayant une température corporelle spontanément basse présentaient des caractéristiques suggérant une altération de la thermorégulation. MéTHODE: Nous avons mené une étude de cohorte rétrospective monocentrique. Nous avons inclus tou·tes les patient·es adultes ayant bénéficié d'un contrôle de température lors d'une hypothermie après un arrêt cardiaque entre le 1er janvier 2014 et le 30 juin 2020. L'exposition principale était une température corporelle centrale spontanément basse (< 35 °C) au début du traitement de l'hypothermie. Le critère d'évaluation principal était le décès à l'hôpital, et le critère d'évaluation secondaire était de mauvaises issues neurologiques à la sortie de l'hôpital. RéSULTATS: Cinq cent quatre-vingt-dix-sept patient·es adultes, ayant subi des arrêts cardiaques à l'hôpital ou hors de l'hôpital, ont été inclus·es. Les patient·es ayant une température corporelle spontanément basse avaient également une température moyenne légèrement plus basse et des épisodes de fièvre paroxystique transitoires mais contrôlés plus fréquents au cours des premières 24 heures. Dans l'analyse de régression logistique multivariée, une température corporelle spontanément basse était associée à une probabilité plus élevée de décès à l'hôpital (rapport de cotes, 2,9; intervalle de confiance à 95 %, 1,9 à 4,2; P < 0,001). CONCLUSION: Dans cette étude de cohorte rétrospective monocentrique, une température corporelle centrale spontanément basse a été associée à de mauvais devenirs après un arrêt cardiaque. Les patient·es présentant une température corporelle spontanément basse présentaient également des caractéristiques suggérant une altération de la thermorégulation. D'autres recherches sont nécessaires pour déterminer si la température corporelle lors de la présentation reflète la robustesse de la physiologie sous-jacente des patient·es et la gravité de la lésion cérébrale après un arrêt cardiaque.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Hipotermia Induzida , Hipotermia , Adulto , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , Hipotermia Induzida/efeitos adversos , Parada Cardíaca/terapia , Regulação da Temperatura Corporal
6.
J Intensive Care Med ; 39(7): 623-627, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38176890

RESUMO

PURPOSE: Temperature targets in patients with cardiac arrest and return of spontaneous circulation (ROSC) have changed. Changes to higher temperature targets have been associated with higher breakthrough fevers and mortality. A post-ROSC normothermia bundle was developed to improve compliance with temperature targets. METHODS: In August 2021, "ad hoc" normothermia at the discretion of the attending intensivist was initiated. In December 2021, a post-ROSC normothermia protocol was implemented, incorporating a rigorous, stepwise approach to fever prevention (temperature ≥ 37.8). We conducted a before-after cohort study of all adult patients post-ROSC who survived to intensive care unit admission between August 1, 2021, and April 1, 2022. They were divided into "ad hoc" and "protocol" groups. Clinical outcomes compared included fevers, active cooling, and paralytic use. RESULTS: Fifty-eight post-ROSC patients were admitted; 24 in the "ad hoc" and 34 in the "protocol" groups. Patient demographics were similar between groups. The "ad hoc" group had more shockable rhythms (67% vs 24%, P = .001) and cardiac catheterizations (42% vs 15%, P = .03). The "protocol" group were significantly less likely to have a fever at 40 h (6% vs 40%, P < .001) and 72 h (14% vs 65%, P ≤ .001). Patients in the normothermia "protocol" used significantly less neuromuscular blocking agents (24% vs 50%, P = .05). The normothermia "protocol" resulted in similar mortality (56% vs 58%, P = 1.0). CONCLUSION: Use of a normothermia "protocol" resulted in fewer fevers and less neuromuscular blocker administration compared to "ad hoc" management. A protocolized approach for improved quality of care should be considered in institutions adopting normothermia.


Assuntos
Febre , Pacotes de Assistência ao Paciente , Humanos , Masculino , Feminino , Pacotes de Assistência ao Paciente/normas , Pessoa de Meia-Idade , Idoso , Febre/terapia , Melhoria de Qualidade , Temperatura Corporal , Reanimação Cardiopulmonar/normas , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Unidades de Terapia Intensiva , Cuidados Críticos/normas , Cuidados Críticos/métodos , Protocolos Clínicos/normas , Resultado do Tratamento
7.
Poult Sci ; 102(11): 103043, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741118

RESUMO

The recently detected clade 2.3.4.4 of the highly pathogenic avian influenza (HPAI) H5N8 virus in poultry encouraged us to study the efficacy of the 6 most extensively used saleable H5 poultry vaccinations (bivalent [AI + ND], Re-5 H5N1, H5N1, H5N3, monovalent AI, monovalent ND) with or without aqueous 8% neem (Azadirachta indica) leaf extract as an immunostimulant. One hundred thirty birds were randomly divided into 7 groups. Groups 1, 2, 3, 4, 5, and 6 were divided into 2 subgroups (G1a, G2a, G3a, G4a, G5a, G6a) and (G1b, G2b, G3b, G4b, G5b, G6b) with 10 birds each. Subgroups (G1a, G2a, G3a, G4a, G5a, G6a) received the (bivalent [AI + ND], Re-H5N1, H5N1, H5N3, monovalent AI, monovalent ND) vaccines, while subgroups (G1b, G2b, G3b, G4b, G5b, G6b) received the same previous vaccination but treated with neem leaf extract administrated 2 d before and after vaccination, and G7 with 10 birds was kept unvaccinated as positive control group. Clinical signs of the challenged group showed conjunctivitis, closed eyes, cyanosis in comb and wattle, ocular discharge, and greenish diarrhea, while postmortem lesions showed congested trachea and lung, hemorrhage on the shank, proventriculus, and pancreas; gelatinous fluid submandibular, congestion of all organs (septicemia), mottled spleen. The clinical signs and lesions were mild in neem leaf extract treated with bivalent vaccine and Re-H5N1 while moderate in monovalent vaccine and H5N3 with or without neem leaf extract treated and reached severe in the group immunized with H5N1 with or without neem leaf extract treatment. The protection levels in the bivalent vaccine (AI + ND), Re-5 H5N1, and H5N3 treated with neem leaf extract, were 80%, 80%, and 60%, respectively, while bivalent vaccine (AI + ND), Re-5 H5N1 and H5N3 without treatment were 60%, 60%, and 40%, respectively. The virus shedding was prevented in groups vaccinated with bivalent vaccine and Re-H5N1 vaccine treated with neem leaf extract, while decreased in the group vaccinated with H5N3 with neem leaf extract and Re-H5N1 without neem leaf extract compared with H5N3, H5N1, and monovalent vaccine. The immunological response after vaccination was stronger in the bivalent vaccine group than in the other commercial vaccine groups treated with neem leaf extract, with geometric mean titer (GMTs) of 315.2 and 207.9 at the third and fourth weeks, respectively. The use of immunostimulant antiviral medicinal plants, such as neem, completely protected chicken flocks against HPAI (H5N8) and prevented AI virus shedding, leading us to the conclusion that the use of bivalent vaccines induces a higher immune response than other different commercial vaccines.

8.
Can J Anaesth ; 70(9): 1474-1485, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37344745

RESUMO

PURPOSE: A clinical conflict often presented with hip fracture patients is whether to proceed with timely surgery or delay surgery until a formal echocardiogram is conducted. This study aimed to assess the impact of incorporating point-of-care lung and cardiac ultrasound (LUCAS) scans as part of the preoperative assessment for hip fracture patients. METHODS: We recruited 225 consecutive adult patients booked for urgent hip arthroplasty surgery. A LUCAS scan was performed for each patient. The anesthesiologists were asked to provide their anesthetic plans before and after acknowledging the results of the LUCAS scans. The primary endpoint was a composite outcome of changes to the anesthetic plan. The secondary outcomes included anesthesiologists' opinions of the LUCAS scans. RESULTS: One-hundred-ninety-eight patients were included. The majority of LUCAS findings were not severe. A common abnormal finding was hypovolemia (31%). One-hundred-and-six anesthetic management decisions were changed, with 59 of these changes being an escalation of the anesthetic plan, and 47 of these changes being a de-escalation. Eighty-three percent of anesthesiologists agreed that LUCAS affirmed their anesthetic plans and should be an integral part of the perioperative assessment. CONCLUSION: This study found that LUCAS scans did not significantly alter the anesthetic plan for hip fracture patients. Nevertheless, LUCAS scans can rule out severe cardiopulmonary conditions and allow for both escalation and de-escalation of care. In the setting of early hip surgery, LUCAS presents a viable option in selected patients to address the unmet need to allow for both timely surgery and comprehensive patient evaluation. STUDY REGISTRATION: ClinicalTrials.gov (NCT03275129); registered 8 July 2018.


RéSUMé: OBJECTIF: Une interrogation clinique qui existe souvent avec les patient·es se présentant avec une fracture de hanche est de savoir s'il faut procéder à une intervention chirurgicale rapidement ou retarder la chirurgie jusqu'à ce qu'un échocardiogramme formel soit réalisé. Cette étude visait à évaluer l'impact de l'intégration de l'échographie ciblée pulmonaire et cardiaque (LUCAS, Lung and Cardiac ultrasound) dans le cadre de l'évaluation préopératoire des personnes ayant subi une fracture de la hanche. MéTHODE: Nous avons recruté 225 patient·es adultes consécutif·ves devant bénéficier d'une arthroplastie urgente de la hanche. Une échographie de type LUCAS a été réalisée pour chaque patient·e. On a demandé aux anesthésiologistes de fournir leurs plans anesthésiques avant et après avoir pris connaissance des résultats des échographies de type LUCAS. Le critère d'évaluation principal était un résultat composite des modifications apportées au plan anesthésique. Les critères d'évaluation secondaires comprenaient les opinions des anesthésiologistes sur les échographies de type LUCAS. RéSULTATS: Cent quatre-vingt-dix-huit patient·es ont été inclus·es. La majorité des résultats de l'échographie de type LUCAS n'étaient pas graves. Un résultat anormal courant était l'hypovolémie (31 %). Cent six décisions de prise en charge anesthésique ont été modifiées, 59 de ces changements étant une escalade du plan anesthésique et 47 de ces changements étant une réduction. Quatre-vingt-trois pour cent des anesthésiologistes ont convenu que l'échographie de type LUCAS confirmait leurs plans anesthésiques et devrait faire partie intégrante de l'évaluation périopératoire. CONCLUSION: Cette étude a révélé que les échographies de type LUCAS ne modifiaient pas de manière significative le plan anesthésique pour les patient·es se présentant avec une fracture de hanche. Néanmoins, les échographies de type LUCAS peuvent exclure des affections cardiopulmonaires graves et permettre à la fois d'augmenter ou de réduire les soins périopératoires. Dans le cadre d'une chirurgie précoce de la hanche, l'échographie de type LUCAS présente une option viable chez une patientèle sélectionnée pour répondre à un besoin non satisfait afin de permettre à la fois une chirurgie rapide et une évaluation complète des patient·es. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03275129); enregistrée le 8 juillet 2018.


Assuntos
Anestésicos , Fraturas do Quadril , Adulto , Humanos , Estudos Prospectivos , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Pulmão
9.
Phys Chem Chem Phys ; 25(13): 9532-9547, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36939088

RESUMO

A novel thiourea derivative has been successfully synthesized via green routes and fully characterized by FT-IR, 1H, 13C-NMR, and elemental analysis. The synthetic inhibitor 2-amino-N-(phenylcarbamothioyl) benzamide (APCB) was assessed as a corrosion inhibitor for mild steel (MS) in 0.5 M H2SO4. Various electrochemical techniques, such as electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP), have been used to evaluate inhibition efficiency. As a result, EIS and PDP agreed with each other, indicating that APCB exhibits an inhibition performance that exceeds 96% at a concentration of 2 × 10-4 M and increases with an increase in temperature up to 98% at 333 K. However, PDP measurements showed that APCB is a mixed type of inhibitor. In addition, SEM, EDX, AFM, and contact angle measurements were used as a topological surface characterization technique that confirmed the formation of a protective layer over the MS surface. Additionally, the complex formation was thoroughly confirmed by UV-Vis measurements. The adsorption of APCB proved the highest compliance with the Langmuir adsorption isotherm. Furthermore, density functional theory (DFT) calculations were conducted to establish the correlation between the electronic structure and excellent inhibition efficiency. Moreover, molecular dynamics (MD) simulations were used to find interaction energy in different media. Finally, the adsorption affinity of the MS surface for different concentrations of APCB was verified via Monte Carlo (MC) simulations. Owing to the outcomes of this study, it is remarkable that APCB, with its low cost and simple synthesis, might be an exceptionally prominent option for mild steel protection.

10.
Environ Sci Pollut Res Int ; 30(14): 42390-42398, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36648717

RESUMO

Diabetes mellitus (DM) is a dysmetabolic disease characterized by chronic hyperglycemia. In the developed countries, DM is the commonest life style disease that affects both old and young age. Nod-like receptor protein-3 (NLRP3)-mediated pyroptosis may in fact aid in the development of diabetic complications. Quercetin is a natural flavonoid, can be present in natural foods and plants. Many studies have reported the antioxidant role of quercetin on different tissues, but its effects on NLRP3-mediated pyroptosis in diabetic lung are unclear. The current study aimed to assess quercetin's protective effects on lung function, oxidative stress, and NLRP3-mediated pyroptosis in Wister rats exposed to streptozotocin (STZ)-induced DM. Forty male Wister rats were randomly allocated into four equal groups. The groups of rats were as follows: group 1 (G1) was kept under normal control conditions; G2 was injected I/P quercetin at a dose of 30 mg/kg b.wt., daily for 30 days; G3 and G4 were injected with a single dose of streptozotocin (STZ) 50 mg/kg b.wt. I/P to induce DM. After 72-h post diabetes induction, the rats of G4 were treated with quercetin as a manner in the second group. The results showed that quercetin ameliorates the pulmonary dysfunctions caused by DM through restoring the levels of glucose, insulin, and arterial blood gases, as well as the oxidative markers. Also, NLRP3-pyroptosis-mediated IL1ß was inhibited. Quercetin also reduces the effect of DM on the lung by decreasing the pathological changes in the lung. In conclusion, NLRP3 inflammasome-induced pyroptosis may aggravate lung injury in diabetic rats. Quercetin has the potential to ameliorate diabetes induced pulmonary dysfunction by targeting NLRP3.


Assuntos
Diabetes Mellitus Experimental , Quercetina , Ratos , Animais , Quercetina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Estreptozocina/efeitos adversos , Ratos Wistar , Transdução de Sinais
11.
BMJ Open ; 12(11): e062988, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36332945

RESUMO

INTRODUCTION: Rapid sequence intubation (RSI) is an advanced airway technique to perform endotracheal intubation in patients at high risk of aspiration. Although RSI is recognised as a life-saving technique and performed by many physicians in various settings (emergency departments, intensive care units), there is still a lack of consensus on various features of the procedure, most notably patient positioning. Previously, experts have commented on the unique drawbacks and benefits of various positions and studies have been published comparing patient positions and how it can affect endotracheal intubation in the context of RSI. The purpose of this systematic review is to compile the existing evidence to understand and compare how different patient positions can potentially affect the success of RSI. METHODS AND ANALYSIS: We will use MEDLINE, EMBASE and the Cochrane Library to source studies from 1946 to 2021 that evaluate the impact of patient positioning on endotracheal intubation in the context of RSI. We will include randomised control trials, case-control studies, prospective/retrospective cohort studies and mannequin simulation studies for consideration in this systematic review. Subsequently, we will generate a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram to display how we selected our final studies for inclusion in the review. Two independent reviewers will complete the study screening, selection and extraction, with a third reviewer available to address any conflicts. The reviewers will extract this data in accordance with our outcomes of interest and display it in a table format to highlight patient-relevant outcomes and difficulty airway management outcomes. We will use the Risk of Bias tool and the Newcastle-Ottawa Scale to assess included studies for bias. ETHICS AND DISSEMINATION: This systematic review does not require ethics approval, as all patient-centred data will be reported from published studies. PROSPERO REGISTRATION NUMBER: CRD42022289773.


Assuntos
Intubação Intratraqueal , Indução e Intubação de Sequência Rápida , Humanos , Intubação Intratraqueal/métodos , Posicionamento do Paciente , Estudos Prospectivos , Projetos de Pesquisa , Estudos Retrospectivos , Revisões Sistemáticas como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Front Immunol ; 13: 928018, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052070

RESUMO

Selective differentiation of CD4+ T helper (Th) cells into specialized subsets such as Th1 and Th2 cells is a key element of the adaptive immune system driving appropriate immune responses. Besides those canonical Th-cell lineages, hybrid phenotypes such as Th1/2 cells arise in vivo, and their generation could be reproduced in vitro. While master-regulator transcription factors like T-bet for Th1 and GATA-3 for Th2 cells drive and maintain differentiation into the canonical lineages, the transcriptional architecture of hybrid phenotypes is less well understood. In particular, it has remained unclear whether a hybrid phenotype implies a mixture of the effects of several canonical lineages for each gene, or rather a bimodal behavior across genes. Th-cell differentiation is a dynamic process in which the regulatory factors are modulated over time, but longitudinal studies of Th-cell differentiation are sparse. Here, we present a dynamic transcriptome analysis following Th-cell differentiation into Th1, Th2, and Th1/2 hybrid cells at 3-h time intervals in the first hours after stimulation. We identified an early bifurcation point in gene expression programs, and we found that only a minority of ~20% of Th cell-specific genes showed mixed effects from both Th1 and Th2 cells on Th1/2 hybrid cells. While most genes followed either Th1- or Th2-cell gene expression, another fraction of ~20% of genes followed a Th1 and Th2 cell-independent transcriptional program associated with the transcription factors STAT1 and STAT4. Overall, our results emphasize the key role of high-resolution longitudinal data for the characterization of cellular phenotypes.


Assuntos
Células Th1 , Células Th2 , Diferenciação Celular/genética , Células Híbridas , Ativação Linfocitária
13.
Neurol India ; 70(4): 1427-1434, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36076639

RESUMO

Background: Extradural transcranial release of the meningo-orbital band occupying the lateral part of the superior orbital fissure is used to approach the orbital apex and middle cranial fossa. The authors tested the feasibility of the release of the meningo-orbital band via an endonasal transmaxillary approach. Materials and Methods: Five injected cadaveric heads were assessed for dimensions of superior orbital fissure by computerized tomography. An endonasal transsphenoid transpterygoid approach was done to the superior orbital fissure and annulus of Zinn medially, down to the maxillary nerve. The periorbita was dissected superolaterally to expose the greater wing of the sphenoid and the meningo-orbital band. The superior orbital fissure was decompressed inferiorly by drilling the greater wing of the sphenoid and the maxillary strut after transposition of the maxillary nerve. The meningoorbital band was cut at the junction of the lateral part of the superior orbital fissure and the periorbita exposing the frontotemporal dural junction. The edge of the lesser wing of the sphenoid was drilled toward the annulus of Zinn and the optic canal. The temporal lobe dura was separated from the periorbita and lateral cavernous dural wall at the meningo-orbital band and the ophthalmic nerve. Results: The superior orbital fissure had an oblique angle (mean: 39 ± 2.75 degrees) to the midsagittal plane, the length of its lateral part corresponding to the meningo-orbital band was (mean: 6.08 ± 2.58 mm) and the distance from its lateral end to midline was (mean 2.97 ± 0.11 cm). The meningo-orbital band was released in 10 cadaveric head sides with a distinct plane between the periorbita and the dura propria. Transmaxillary endoscopy provided less orbital retraction and better visualization of the lateral wall of the cavernous sinus. Conclusion: Endonasal transmaxillary release of the meningoorbital band is feasible, allowing exposure of the orbital apex and the middle cranial fossa.


Assuntos
Endoscopia , Cadáver , Seio Cavernoso , Endoscopia/métodos , Estudos de Viabilidade , Humanos , Procedimentos Neurocirúrgicos/métodos
14.
Neurol India ; 70(3): 890-896, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864615

RESUMO

Background: Data on the outcomes of microsurgical resection (SR) and stereotactic gamma knife radiosurgery (GKRS) in patients with trigeminal neuralgia associated with small petrous apex meningiomas are scarce. Objective: We conducted this study to evaluate the pain relief, tumor control, and procedure costs following SR and GKRS for small petroclival meningiomas (less than 3 cm in maximal diameter) using real-world data from our center in Egypt. Material and Methods: We conducted a retrospective cohort study of 47 patients with small petrous apex meningiomas presenting with intractable trigeminal nerve pain (SR: n = 22 and GKRS: n = 25). Data regarding pain relief on Barrow Neurological Institute (BNI), procedure cost, and tumor control were retrieved and analyzed using appropriate statistical tests. Results: Patients who underwent SR had lower median BNI pain intensity scores compared to those patients who underwent GKRS, and a significantly higher proportion of patients in the SR group had good BNI scores compared to those in GKRS group (P < 0.05); however, the total costs of SR were significantly less than GKRS (30,519$ vs. 92,372$, respectively). Conclusion: Both SR and GKRS provide pain relief and tumor control in patients with trigeminal neuralgia associated with petrous apex meningioma. However, in the present study, SR achieved better pain control and was more affordable than GKRS.


Assuntos
Neoplasias Meníngeas , Meningioma , Radiocirurgia , Neoplasias da Base do Crânio , Doenças do Nervo Trigêmeo , Neuralgia do Trigêmeo , Estudos de Coortes , Seguimentos , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/radioterapia , Meningioma/cirurgia , Microcirurgia , Dor/cirurgia , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias da Base do Crânio/complicações , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/cirurgia , Resultado do Tratamento , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/cirurgia
15.
BMC Infect Dis ; 22(1): 537, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35692034

RESUMO

BACKGROUND: Passive immunization against SARS-CoV-2 limits viral burden and death from COVID-19; however, it poses a theoretical risk of disease exacerbation through antibody-dependent enhancement (ADE). ADE after anti-SARS-CoV2 antibody treatment has not been reported, and therefore the potential risk and promoting factors remain unknown. CASE PRESENTATION: A 75-year-old female was admitted to the emergency room with recurrent, unexplained bruises and leukocytopenia, anemia, and thrombocytopenia. Evaluation of a bone marrow biopsy established the diagnosis of an acute promyelocytic leukemia (APL). SARS-CoV-2 RT-PCR testing of nasal and throat swabs on admission was negative. During the routine SARS-CoV-2 testing of inpatients, our patient tested positive for SARS-CoV-2 on day 14 after admission without typical COVID-19 symptoms. Due to disease- and therapy-related immunosuppression and advanced age conferring a high risk of progressing to severe COVID-19, casirivimab and imdevimab were administered as a preemptive approach. The patient developed immune activation and cytokine release syndrome (CRS) occurring within four hours of preemptive anti-SARS-CoV2 antibody (casirivimab/imdevimab) infusion. Immune activation and CRS were evidenced by a rapid increase in serum cytokines (IL-6, TNFα, IL-8, IL-10), acute respiratory insufficiency, and progressive acute respiratory distress syndrome. DISCUSSION AND CONCLUSION: The temporal relationship between therapeutic antibody administration and the rapid laboratory, radiological, and clinical deterioration suggests that CRS was an antibody-related adverse event, potentially exacerbated by APL treatment-mediated differentiation of leukemic blasts and promyelocytes. This case highlights the need for careful assessment of life-threatening adverse events after passive SARS-CoV-2 immunization, especially in the clinical context of patients with complex immune and hematological landscapes.


Assuntos
COVID-19 , Leucemia Promielocítica Aguda , Síndrome do Desconforto Respiratório , Idoso , Anticorpos Monoclonais Humanizados , COVID-19/complicações , COVID-19/diagnóstico , Teste para COVID-19 , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Feminino , Humanos , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , SARS-CoV-2
16.
Front Med (Lausanne) ; 9: 810825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492302

RESUMO

Importance: Accurate monitoring of core body temperature is integral to targeted temperature management (TTM) following cardiac arrest. However, there are no reliable non-invasive methods for monitoring temperature during TTM. Objectives: We compared the accuracy and precision of a novel non-invasive Zero-Heat-Flux Thermometer (SpotOn™) to a standard invasive esophageal probe in a cohort of patients undergoing TTM post-cardiac arrest. Design Setting and Participants: We prospectively enrolled 20 patients undergoing post-cardiac arrest care in the intensive care units at the London Health Sciences Centre in London, Canada. A SpotOn™ probe was applied on each patient's forehead, while an esophageal temperature probe was inserted, and both temperature readings were recorded at 1-min intervals for the duration of TTM. Main outcomes and Measures: We compared the SpotOn™ and esophageal monitors using the Bland-Altman analysis and the Pearson correlation, with accuracy set as a primary outcome. Secondary outcomes included precision and correlation. Bias exceeding 0.1°C and limits of agreement exceeding 0.5°C were considered clinically important. Results: Sixteen (80%) of patients had complete data used in the final analysis. The median (interquartile range) duration of recording was 38 (12-56) h. Compared to the esophageal probe, SpotOn™ had a bias of 0.06 ± 0.45°C and 95% limits of agreement of -0.83 to 0.95°C. The Pearson correlation coefficient was 0.97 (95% confidence interval 0.9663-0.9678), with a two-tailed p < 0.0001. Conclusion and Relevance: The SpotOn™ is an accurate method that may enable non-invasive monitoring of core body temperature during TTM, although its precision is slightly worse than the predefined 0.5°C when compared to invasive esophageal probe.

18.
19.
Z Rheumatol ; 81(8): 635-641, 2022 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-35380250

RESUMO

Helper T (Th) cells play a decisive role in triggering and maintaining chronic rheumatic inflammation. Via secretion of proinflammatory cytokines and expression of costimulatory cell surface molecules, Th lymphocytes coordinate the recruitment and activation of effector cells, which are ultimately responsible for the immunopathology and tissue destruction. However, therapeutic approaches aimed at eliminating Th cells were unsuccessful due to their lack of selectivity. At the German Rheumatism Research Center (Deutsches Rheuma-Forschungszentrum, DRFZ), we are working to improve the understanding of the Th cells involved in chronic inflammatory reactions. Based on this understanding, our aim is to develop novel treatment strategies that selectively target the pathogenic Th lymphocytes causing rheumatic inflammation. The current article summarizes the DRFZ's research activities on this subject.


Assuntos
Doenças Reumáticas , Linfócitos T , Citocinas , Humanos , Inflamação/patologia , Linfócitos T/patologia , Linfócitos T Auxiliares-Indutores
20.
Clin Anat ; 35(4): 526-528, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35218594

RESUMO

Human cadaveric donors are essential for research in the anatomical sciences. However, many research papers in the anatomical sciences often omit a statement regarding the ethical use of the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To rectify this issue, 22 editors-in-chief of anatomical journals, representing 17 different countries, developed standardized and simplified language that can be used by authors of studies that use human cadaveric tissues. The goal of these editor recommendations is to standardize the writing approach by which the ethical use of cadaveric donors is acknowledged in anatomical studies that use donor human cadavers. Such sections in anatomical papers will help elevate our discipline and promote standardized language use in others non anatomy journals and also other media outlets that use cadaveric tissues.


Assuntos
Anatomia , Doadores de Tecidos , Cadáver , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...