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1.
RSC Adv ; 14(16): 11557-11569, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38601708

RESUMO

Here we present the magnetic properties of two cobalt complexes formulated as: [Co(SCN)2(L)2] (1) and (H2L)2[Co(SCN)4]·H2O (2) (L = 1-(2-pyrimidyl)piperazine). The two compounds contain isolated tetrahedral CoII complexes with important intermolecular interactions that lead to the presence of a canted antiferromagnetic order below 11.5 and 10.0 K, with coercive fields at 2 K of 38 and 68 mT, respectively. Theoretical calculations have been used to explain this behaviour. Hirshfeld surface analysis shows the presence of strong intermolecular interactions in both compounds. The crystal geometries were used for geometry optimization using the DFT method. From the topological properties, electrostatic potential maps and molecular orbital analysis, information about the noncovalent interaction and chemical reactivity was obtained.

2.
STAR Protoc ; 5(2): 102988, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38635395

RESUMO

Respirometry is a technique for studying mitochondrial function that has proven compatibility with ≥0.5 mg of brain tissue. Here, we present a protocol for assessing oxygen consumption and H2O2 production rates in hippocampal tissue using the Oroboros O2k system. We describe steps for brain harvesting, tissue preparation, hippocampal microdissection, and respirometry assays. This approach has been valuable to study the metabolism of dentate granule cells of the hippocampus and could be applicable to other brain subregions. For complete details on the use and execution of this protocol, please refer to Rose et al.1.

3.
ACS Photonics ; 11(4): 1673-1683, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38645995

RESUMO

High-order harmonic generation (HHG) arising from the nonperturbative interaction of intense light fields with matter constitutes a well-established tabletop source of coherent extreme-ultraviolet and soft X-ray radiation, which is typically emitted as attosecond pulse trains. However, ultrafast applications increasingly demand isolated attosecond pulses (IAPs), which offer great promise for advancing precision control of electron dynamics. Yet, the direct generation of IAPs typically requires the synthesis of near-single-cycle intense driving fields, which is technologically challenging. In this work, we theoretically demonstrate a novel scheme for the straightforward and compact generation of IAPs from multicycle infrared drivers using hollow capillary fibers (HCFs). Starting from a standard, intense multicycle infrared pulse, a light transient is generated by extreme soliton self-compression in a HCF with decreasing pressure and is subsequently used to drive HHG in a gas target. Owing to the subcycle confinement of the HHG process, high-contrast IAPs are continuously emitted almost independently of the carrier-envelope phase (CEP) of the optimally self-compressed drivers. This results in a CEP-robust scheme which is also stable under macroscopic propagation of the high harmonics in a gas target. Our results open the way to a new generation of integrated all-fiber IAP sources, overcoming the efficiency limitations of usual gating techniques for multicycle drivers.

4.
Med Vet Entomol ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554285

RESUMO

Scorpionism is an increasing public health problem in the world. Although no specific methodology or product is currently available for the control of those arachnids, the use of insecticides could be an effective tool. Chlorpyrifos is one of the insecticides used, but to date, whether scorpions recognise surfaces with that insecticide and how it affects their physiology and/or biochemistry is unknown. In the present study, we observed that scorpions recognise surfaces with 0.51 and 8.59 µg/cm2 of chlorpyrifos and avoid those areas. The 0.51 µg/cm2 concentration produced a decrease in acetylcholinesterase and an increase in catalase, superoxide dismutase and glutathione S-transferase, whereas the 8.59 µg/cm2 concentration evoked a decrease in acetylcholinesterase and an increase in catalase and glutathione S-transferase. Using the comet assay, we observed that the insecticide at 0.17, 0.51 and 8.59 µg/cm2 caused DNA damage. Finally, we found that the insecticide does not generate significant variations in glutathione peroxidase, glutathione reductase, the amount of protein or lipid peroxidation. The present results offer a comprehensive understanding of how scorpions respond, both at the biochemical and behavioural levels, when exposed to insecticides.

5.
Chemistry ; : e202400410, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483106

RESUMO

We have prepared and characterized three coordination polymers formulated as [Dy2(C6O4Cl2)3(fma)6] ⋅ 4.5fma (1) and [Dy2(C6O4X2)3(fma)6] ⋅ 4fma ⋅ 2H2O with X=Br (2) and Cl (3), where fma=formamide and C6O4X2 2-=3,6-disubstituted-2,5-dihydroxy-1,4-benzoquinone dianion with X=Cl (chloranilato) and Br (bromanilato). Compounds 1 and 3 are solvates obtained with slow and fast precipitation methods, respectively. Compounds 2 and 3 are isostructural and only differ in the X group of the anilato ligand. The three compounds present (6,3)-gon two-dimensional hexagonal honey-comb structures. Magnetic measurements indicate that the three compounds show slow relaxation of the magnetization at low temperatures when a continuous magnetic field is applied, although with different relaxation times and energy barriers depending on X and the crystallisation molecules. Compounds 1-3 represent the first examples of anilato-based lattices with formamide and field-induced slow relaxation of the magnetization.

6.
Inorg Chem ; 63(14): 6161-6172, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38526851

RESUMO

We present a bifunctional heptanuclear cobalt(II)/cobalt(III) molecular complex formulated as [Co7(µ3-OH)4(H2L1)2(HL2)2](NO3)6·6H2O (1) (where H5L1 is 2,2'-(((1E,1'E)-((2-hydroxy-5-methyl-1,3-phenylene)bis(methanylylidene))bis(azanylylidene))bis(propane-1,3-diol)) and H2L2 is 2-amino-1,3-propanediol). Compound 1 has been characterized by single-crystal X-ray diffraction analysis along with other spectral and magnetic measurements. Structural analysis indicates that 1 contains a mixed-valence Co7 cluster where a central Co(II) ion is connected to six different Co centers (four CoIII and two CoII ions) by four µ3-OH groups, giving rise to a planar heptanuclear cluster that resembles a molecular fragment of a layered double hydroxide (LDH). Two triply deprotonated (H2L1)3- ligands form the outer side of the cluster while two singly deprotonated (HL2)- ligands are located at the top and bottom of the central heptanuclear core. Variable temperature magnetic measurements indicate the presence of weak ferromagnetic CoII···CoII interactions (J = 3.53(6) cm-1) within the linear trinuclear CoII cluster. AC susceptibility measurements show that 1 is a field-induced single-molecule magnet (SMM) with τ0 = 8.2(7) × 10-7 s and Ueff = 11.3(4) K. The electrocatalytic hydrogen evolution reaction (HER) activity of 1 in homogeneous phase shows an overpotential of 455 mV, with a Faradaic efficiency of 81% and a TOF of 8.97 × 104 µmol H2 h-1 mol-1.

7.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38521440

RESUMO

INTRODUCTION AND OBJECTIVES: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. METHODS: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. RESULTS: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. CONCLUSIONS: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

8.
Arch Cardiol Mex ; 94(1): 15-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38507305

RESUMO

BACKGROUND: Cardiac resynchronization therapy (CRT) has been established as an effective therapy for heart failure with reduced ejection fraction. Randomized clinical trials have shown its impact on mortality and HF hospitalizations, as well as improvement of symptoms and quality of life. OBJECTIVES: Finding clinical, electrocardiographic, and echocardiographic variables that may predict the response to cardiac resynchronization therapy (CRT). METHODS: We performed a single-center, observational, analytic, and retrospective study that included 102 patients with heart failure (HF) diagnosis who underwent CRT according to guideline-directed therapy from January 2010 to April 2020 in a third-level center. CRT response was defined as an improvement of New York Heart Association functional class in at least 1 category associated with a recovery of ≥ 5% in the left ventricular ejection fraction (LVEF). RESULTS: Our study population was 102 patients of which 61 (59.8%) were men. The mean age at HF diagnosis was 54 ± 18.7 years. Ischemic heart disease was the etiology in 37 (36.3%) cases. Fifty-one (50%) patients were classified as responders. Responders had wider QRS, and lower LVEF and right ventricular fractional area change at baseline. After CRT, responders had a greater reduction of QRS duration, and improvement in LVEF, global longitudinal strain, and echocardiographic dyssynchrony parameters. Multivariate regression analysis showed that left bundle branch block (LBBB), left ventricular end-diastolic volume (LVEDV), tricuspid annular plane systolic excursion (TAPSE), and baseline difference of pre-ejection periods were predictors of a positive response to CRT in this population. CONCLUSIONS: LBBB, TAPSE, LVEDV, and pre-ejection time difference are independent variables that can predict adequate response to CRT.


ANTECEDENTES: La terapia de resincronización cardíaca (TRC) se ha establecido como una terapia efectiva para la insuficiencia cardíaca con fracción de eyección reducida. Ensayos clínicos aleatorizados han demostrado su impacto en la mortalidad y hospitalizaciones por insuficiencia cardíaca, así como la mejora de los síntomas y la calidad de vida. OBJETIVOS: Determinar las variables clínicas, electrocardiográficas y ecocardiográficas que puedan predecir la respuesta a la terapia de resincronización cardíaca (TRC). MÉTODO: Estudio unicéntrico, observacional, analítico, retrospectivo, que incluyó 102 pacientes con diagnóstico de IC sometidos a TRC y terapia dirigida por guías, de enero de 2010 a abril de 2020, en un centro de tercer nivel. La respuesta a TRC fue definida como mejoría de la clase funcional de la New York Heart Association en al menos 1 categoría, asociado con una recuperación ≥ 5% en la fracción de expulsión del ventrículo izquierdo (FEVI). RESULTADOS: Incluimos a 102 pacientes, 61 (59.8%) fueron hombres. El promedio de edad al diagnóstico de IC fue 54 ± 18.7 años. La cardiopatía isquémica fue la etiología en 37 (36.3%) pacientes. 51 (50%) pacientes, fueron clasificados como respondedores. Los respondedores presentaron QRS amplio, menor FEVI y menor fracción de acortamiento del ventrículo derecho al inicio del estudio. Después de la TRC, los respondedores tuvieron una mayor reducción en la duración del QRS, mejoría en la FEVI, strain longitudinal global y parámetros de disincronía ecocardiográfica. El análisis de regresión multivariado mostró que el bloqueo de rama izquierdo (BRI), el volumen telediastólico del ventrículo izquierdo (VTDVI) la excursión sistólica del plano anular tricuspídeo (TAPSE) y la diferencia basal del período expulsivo fueron predictores de respuesta positiva a TRC. CONCLUSIONES: BRI, TAPSE, VTDVI y la diferencia basal de períodos preexpulsivos son variables independientes que predicen respuesta adecuada a TRC.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Volume Sistólico/fisiologia , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Função Ventricular Esquerda , Bloqueio de Ramo/terapia
9.
Inorg Chem ; 63(12): 5423-5431, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38483819

RESUMO

A series of two-electron-oxidized cobalt porphyrin dimers have been synthesized upon controlled oxidations using halogens. Rather unexpectedly, X-ray structures of two of these complexes contain two structurally different low-spin molecules in the same asymmetric unit of their unit cells: one is the metal-centered oxidized diamagnetic entity of the type CoIII(por), while the other one is the ligand-centered oxidized paramagnetic entity of the type CoII(por•+). Spectroscopic, magnetic, and DFT investigations confirmed the coexistence of the two very different electronic structures both in the solid and solution phases and also revealed a ferromagnetic spin coupling between Co(II) and porphyrin π-cation radicals and a weak antiferromagnetic coupling between the π-cation radicals of two macrocycles via the bridge in the paramagnetic complex.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38537173

RESUMO

Nanostructured microelectrodes (NMEs) are an attractive alternative to yield sensitive bioassays in unprocessed samples. However, although valuable for different applications, nanoporous NMEs usually cannot boost the sensitivity of diffusion-limited analyses because of the enlarged Debye length within the nanopores, which reduces their accessibility. To circumvent this limitation, nanopore-free gold NMEs were electrodeposited from 45 µm SU-8 apertures, featuring nanoridged microspikes on a recessed surface of gold thin film while carrying interconnected crown-like and spiky structures along the edge of a SU-8 passivation layer. These structures were grown onto ultradense, vertical array chips that offer a promising strategy for translating reproducible, high-resolution, and cost-effective sensors into real-world applications. The NMEs yielded reproducible analyses, while machine learning allowed us to predict the analytical responses from NME electrodeposition data. By taking advantage of the high surface area and accessible structure of the NMEs, these structures provided a sensitivity for [Fe(CN)6]3-/4- that was 5.5× higher than that of bare WEs while also delivering a moderate antibiofouling property in undiluted human plasma. As a proof of concept, these electrodes were applied toward the fast (22 min) and simple determination of Staphylococcus aureus by monitoring the oxidation of [Fe(CN)6]4-, which acted as a cellular respiration rate redox reporter. The sensors also showed a wide dynamic range, spanning 5 orders of magnitude, and a calculated limit of detection of 0.2 CFU mL-1.

11.
AACE Clin Case Rep ; 10(2): 63-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523848

RESUMO

Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

13.
Cryst Growth Des ; 24(5): 2235-2265, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38463618

RESUMO

Metal-organic frameworks (MOFs), formed by the combination of both inorganic and organic components, have attracted special attention for their tunable porous structures, chemical and functional diversities, and enormous applications in gas storage, catalysis, sensing, etc. Recently, electronic applications of MOFs like electrocatalysis, supercapacitors, batteries, electrochemical sensing, etc., have become a major research topic in MOF chemistry. However, the low electrical conductivity of most MOFs represents a major handicap in the development of these emerging applications. To overcome these limitations, different strategies have been developed to enhance electrical conductivity of MOFs for their implementation in electronic devices. In this review, we outline all these strategies employed to increase the electronic conduction in both intrinsically (framework-modulated) and extrinsically (guests-modulated) conducting MOFs.

14.
Radiographics ; 44(4): e230158, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38451847

RESUMO

Chronic subdural hematoma (CSDH) is a prevalent medical condition with potentially severe consequences if left untreated. While surgical removal has traditionally been the standard approach for treatment, middle meningeal artery (MMA) embolization has emerged as a promising minimally invasive alternative to reduce recurrences. This comprehensive review provides the general radiology community with an overview of MMA embolization as a therapeutic option for managing CSDH. The authors base their insights on existing evidence and their institutional experience. This overview encompasses the pathophysiology of CSDH as well as the potential advantages and limitations, safety profile, and potential complications of MMA embolization as compared with surgical treatment. The imaging findings seen before and after MMA, as well as insights into the procedural techniques used at the authors' institution, are described. On the basis of reports in the current literature, MMA embolization appears to be a safe and effective therapeutic option for managing CSDH, especially in patients who are unsuitable for surgery or at risk for recurrence. Nonetheless, further research is needed to validate these findings. Results from ongoing clinical trials hold promise for future validation and the establishment of scientific evidence. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Chatterjee in this issue.


Assuntos
Embolização Terapêutica , Hematoma Subdural Crônico , Humanos , Resultado do Tratamento , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/terapia , Hematoma Subdural Crônico/etiologia , Artérias Meníngeas/diagnóstico por imagem , Artérias Meníngeas/cirurgia , Embolização Terapêutica/métodos , Cabeça
15.
Cell Calcium ; 119: 102854, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430790

RESUMO

The necroptotic effector molecule MLKL accumulates in neurons over the lifespan of mice, and its downregulation has the potential to improve cognition through neuroinflammation, and changes in the abundance of synaptic proteins and enzymes in the central nervous system. Notwithstanding, direct evidence of cell-autonomous effects of MLKL expression on neuronal physiology and metabolism are lacking. Here, we tested whether the overexpression of MLKL in the absence of cell death in the neuronal cell line Neuro-2a recapitulates some of the hallmarks of aging at the cellular level. Using genetically-encoded fluorescent biosensors, we monitored the cytosolic and mitochondrial Ca2+ levels, along with the cytosolic concentrations of several metabolites involved in energy metabolism (lactate, glucose, ATP) and oxidative stress (oxidized/reduced glutathione). We found that MLKL overexpression marginally decreased cell viability, however, it led to reduced cytosolic and mitochondrial Ca2+ elevations in response to Ca2+ influx from the extracellular space. On the contrary, Ca2+ signals were elevated after mobilizing Ca2+ from the endoplasmic reticulum. Transient elevations in cytosolic Ca2+, mimicking neuronal stimulation, lead to higher lactate levels and lower glucose concentrations in Neuro-2a cells when overexpressing MLKL, which suggest enhanced neuronal glycolysis. Despite these alterations, energy levels and glutathione redox state in the cell bodies remained largely preserved after inducing MLKL overexpression for 24-48 h. Taken together, our proof-of-concept experiments are consistent with the hypothesis that MLKL overexpression in the absence of cell death contributes to both Ca2+ and metabolic dyshomeostasis, which are cellular hallmarks of brain aging.


Assuntos
Lactatos , Neurônios , Camundongos , Animais , Neurônios/metabolismo , Linhagem Celular , Morte Celular , Lactatos/metabolismo , Lactatos/farmacologia , Glucose/metabolismo , Proteínas Quinases/metabolismo
16.
Infect Dis Now ; 54(2): 104855, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309646

RESUMO

AIM: To assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. METHODS: Adult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. RESULTS: Seroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. CONCLUSIONS: Hospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.


Assuntos
Hepatite C Crônica , Hepatite C , Adulto , Humanos , Hepacivirus/genética , Antivirais/uso terapêutico , Estudos Soroepidemiológicos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hospitais , Anticorpos Anti-Hepatite C/uso terapêutico , Atenção Primária à Saúde
17.
Commun Biol ; 7(1): 219, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388698

RESUMO

Recent evidence suggests a role of sensory neurons expressing the sodium channel Nav1.8 on the energy homeostasis control. Using a murine diphtheria toxin ablation strategy and ad libitum and time-restricted feeding regimens of control or high-fat high-sugar diets, here we further explore the function of these neurons on food intake and on the regulation of gastrointestinal elements transmitting immune and nutrient sensing.The Nav1.8+ neuron ablation increases food intake in ad libitum and time-restricted feeding, and exacerbates daily body weight variations. Mice lacking Nav1.8+ neurons show impaired prandial regulation of gut hormone secretion and gut microbiota composition, and altered intestinal immunity.Our study demonstrates that Nav1.8+ neurons are required to control food intake and daily body weight changes, as well as to maintain physiological enteroendocrine and immune responses and the rhythmicity of the gut microbiota, which highlights the potential of Nav1.8+ neurons to restore energy balance in metabolic disorders.


Assuntos
Microbioma Gastrointestinal , Animais , Camundongos , Peso Corporal , Dieta Hiperlipídica , Ingestão de Alimentos/fisiologia , Microbioma Gastrointestinal/fisiologia , Células Receptoras Sensoriais/metabolismo
18.
Nat Commun ; 15(1): 1096, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321014

RESUMO

Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory condition resulting from monoallelic NLRP3 variants that facilitate IL-1ß production. Although these are gain-of-function variants characterized by hypersensitivity to cell priming, patients with CAPS and animal models of the disease may present inflammatory flares without identifiable external triggers. Here we find that CAPS-associated NLRP3 variants are forming constitutively active inflammasome, which induce increased basal cleavage of gasdermin D, IL-18 release and pyroptosis, with a concurrent basal pro-inflammatory gene expression signature, including the induction of nuclear receptors 4 A. The constitutively active NLRP3-inflammasome of CAPS is responsive to the selective NLRP3 inhibitor MCC950 and its activation is regulated by deubiquitination. Despite their preactivated state, the CAPS inflammasomes are responsive to activation of the NF-κB pathway. NLRP3-inflammasomes with CAPS-associated variants affect the immunometabolism of the myeloid compartment, leading to disruptions in lipids and amino acid pathways and impaired glycolysis, limiting IL-1ß production. In summary, NLRP3 variants causing CAPS form a constitutively active inflammasome inducing pyroptosis and IL-18 release without cell priming, which enables the host's innate defence against pathogens while also limiting IL-1ß-dependent inflammatory episodes through immunometabolism modulation.


Assuntos
Síndromes Periódicas Associadas à Criopirina , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Interleucina-18 , Síndromes Periódicas Associadas à Criopirina/genética , Sulfonamidas/farmacologia , Interleucina-1beta/metabolismo
19.
Science ; 383(6690): eabn3263, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38422184

RESUMO

Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.


Assuntos
Elementos Facilitadores Genéticos , Eutérios , Evolução Molecular , Regulação da Expressão Gênica , Córtex Motor , Neurônios Motores , Proteínas , Vocalização Animal , Animais , Quirópteros/genética , Quirópteros/fisiologia , Vocalização Animal/fisiologia , Córtex Motor/citologia , Córtex Motor/fisiologia , Cromatina/metabolismo , Neurônios Motores/fisiologia , Laringe/fisiologia , Epigênese Genética , Genoma , Proteínas/genética , Proteínas/metabolismo , Sequência de Aminoácidos , Eutérios/genética , Eutérios/fisiologia , Aprendizado de Máquina
20.
Metas enferm ; 27(1): 76-80, Febr. 2024.
Artigo em Espanhol | IBECS | ID: ibc-230210

RESUMO

Objetivo: describir el perfil clínico y sociodemográfico de mujeres con cáncer de mama (CM) en un hospital de tercer nivel del Bajío, México. Métodos: estudio descriptivo transversal con recogida de datos retrospectivos. Se revisaron 262 expedientes clínicos de mujeres con CM, seleccionados mediante muestreo probabilístico. Variables de estudio: edad, lugar de residencia, nivel de estudios, antecedentes familiares y personales de cáncer, comorbilidades, tabaquismo, alcoholismo, tiempo transcurrido desde el diagnóstico, variables clínicas y de tratamiento del CM. Resultados: la media de edad fue de 58,07 años. El 45,8% no tenía antecedentes de cáncer, pero en quienes sí lo tenían, madre y hermana eran los más frecuentes (10,7% y 10,3% respectivamente). El 42,4% de las pacientes presentaba obesidad y el 23,3% tenía más de dos enfermedades crónico-degenerativas. El 87% de las mujeres no presentó metástasis. Un 19,8% se detectó en la etapa IIA. El grado G0 de invasión a ganglios linfáticos fue el más frecuente (35%). La combinación de dos o más tratamientos fue la forma de abordaje terapéutico más común (95,8%). La mayoría de los pacientes fueron dadas de alta por presentar mejoría (71%). Conclusiones: conocer las características sociodemográficas y clínicas de las pacientes con CM puede ayudar a establecer estrategias específicas para la prevención y el manejo en este grupo de pacientes, brindando una atención holística.(AU)


Objective: to describe the clinical and sociodemographic profile of women with breast cancer (BC) in a tertiary hospital from the Bajío area, Mexico. Methods: a descriptive cross-sectional study with retrospective data collection. There was a review of 262 clinical records of women with BC, selected through probability sample. The study variables were age, place of residence, level of studies, family and personal history of cancer, comorbidities, smoking, use of alcohol, time since diagnosis, clinical and BC treatment variables. Results: the mean age was 58.07 years; 45.8% had no history of cancer, but in those who had it, the most frequent were mother and sister (10.7% and 10.3% respectively). 42.4% of the patients presented obesity, and 23.3% had over two chronic degenerative conditions. 87% of women did not present metastasis; 19.8% were detected in the IIA stage; G0 was the most frequent level of invasion of lymph nodes (35%). The most common treatment approach was the combination of two or more treatments (95.8%). The majority of patients were discharged due to improvement (71%). Conclusions: knowing the sociodemographic and clinical characteristics of BC patients can help to establish specific strategies for prevention and management in this group, thus offering holistic care.(AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama , Perfil de Saúde , Demografia , México , Estudos Transversais , Estudos Transversais/estatística & dados numéricos
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