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1.
Cell ; 182(3): 770-785.e16, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32634377

RESUMO

Heterotrimeric G-proteins (Gαßγ) are the main transducers of signals from GPCRs, mediating the action of countless natural stimuli and therapeutic agents. However, there are currently no robust approaches to directly measure the activity of endogenous G-proteins in cells. Here, we describe a suite of optical biosensors that detect endogenous active G-proteins with sub-second resolution in live cells. Using a modular design principle, we developed genetically encoded, unimolecular biosensors for endogenous Gα-GTP and free Gßγ: the two active species of heterotrimeric G-proteins. This design was leveraged to generate biosensors with specificity for different heterotrimeric G-proteins or for other G-proteins, such as Rho GTPases. Versatility was further validated by implementing the biosensors in multiple contexts, from characterizing cancer-associated G-protein mutants to neurotransmitter signaling in primary neurons. Overall, the versatile biosensor design introduced here enables studying the activity of endogenous G-proteins in live cells with high fidelity, temporal resolution, and convenience.


Assuntos
Técnicas de Transferência de Energia por Ressonância de Bioluminescência/instrumentação , Técnicas de Transferência de Energia por Ressonância de Bioluminescência/métodos , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Guanosina Trifosfato/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Motivos de Aminoácidos , Animais , Células Cultivadas , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/química , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Guanosina Trifosfato/química , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Neoplasias/genética , Neoplasias/metabolismo , Neurônios/química , Neurônios/metabolismo , Neurônios/fisiologia , Transdução de Sinais , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
2.
Opt Lett ; 49(9): 2525-2528, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691760

RESUMO

A fundamental parameter to determine how electromagnetic waves interfere is their relative phase, and achieving a fine control over it enables a wide range of interferometric applications. Existing phase control methods rely on modifying the optical path length either by changing the path followed by the light or by altering the thickness or index of refraction of an optical element in the setup. In this Letter, we present a novel, to the best of our knowledge, method, based on acousto-optic modulators (AOMs), which allows adjusting the phase by shifting the frequency of the light in a segment of its path. Since the amount of phase shift depends on the length of the segment, an optical fiber is used to realize a 2π shift. Two experimental implementations are described which deal with different sources of phase fluctuations. The first addresses fluctuations resulting from the optical fiber, while the second tackles unwanted variations originating from the AOMs.

3.
Chemphyschem ; 25(12): e202400074, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38517325

RESUMO

In the framework of the design, synthesis and testing of a library of copper complexes and nanostructured assemblies potentially endowed with antitumor and antiviral activity and useful for several applications, from drugs and related delivery systems to the development of biocidal nanomaterials, we present the detailed spectroscopic investigation of the molecular and electronic structure of copper-based coordination compounds and of a new conjugated system obtained by grafting Cu(I) complexes to gold nanorods. More in detail, the electronic and molecular structures of two Cu complexes and one AuNRs/Cu-complex adduct were investigated by X-ray photoelectron spectroscopy (XPS), synchrotron-induced XPS (SR-XPS) and near edge X-ray absorption spectroscopy (NEXAFS) in solid state, and the local structure around copper ion was assessed by X-ray absorption spectroscopy (XAS) both in solid state and water solution for the AuNRs/Cu-complex nanoparticles. The proposed multi-technique approach allowed to properly define the coordination geometry around the copper ion, as well as to ascertain the molecular structures of the coordination compounds, their stability and modifications upon interaction with gold nanoparticles, by comparing solid state and liquid phase data.

4.
Malar J ; 23(1): 179, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844954

RESUMO

BACKGROUND: In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. METHODS: An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015-2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. RESULTS: During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33-48); median time to consultation was 32 months (IQR:12.5-110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). CONCLUSIONS: None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.


Assuntos
Doadores de Sangue , Malária , Estudos Retrospectivos , Humanos , Doadores de Sangue/estatística & dados numéricos , Malária/diagnóstico , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Seleção do Doador , Espanha , Reação em Cadeia da Polimerase
5.
Sensors (Basel) ; 24(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38543986

RESUMO

INTRODUCTION: The aim of this study was to observe the validity, diagnostic capacity, and reliability of the thermographic technique in the analysis of sensitive and motor sequelae in patients with chronic brain damage. METHOD: A longitudinal descriptive observational study was performed. Forty-five people with impairment in at least one anatomical region participated in and completed this study. All patients who had become infected by SARS-CoV-2 in the past year were excluded. Thermographic measurement was conducted, and the Modified Ashworth Scale and Pressure Pain Threshold was analyzed. RESULTS: A high correlation between two times of thermography data was observed. The Spearman correlations obtained between the Ashworth score on each leg and the temperature given by thermography were all significant. DISCUSSION AND CONCLUSIONS: Despite the above, the Spearman correlations obtained between the PPT in each leg and the temperature offered by thermography were not significant in any of the measurements. For this reason, thermography is a potential tool for the diagnosis and assessment of neuromuscular motor sequelae, but not for sensitive sequelae, after brain injury. Nevertheless, for the time being, no statistical relationship has been observed between the data reported by thermography and PPT; thus, future studies are needed to further investigate these results.


Assuntos
Lesões Encefálicas , Termografia , Humanos , Termografia/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Lesões Encefálicas/diagnóstico , Encéfalo
6.
Infect Immun ; 91(8): e0007223, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37428036

RESUMO

Previously, we showed that Legionella pneumophila secretes rhizoferrin, a polycarboxylate siderophore that promotes bacterial growth in iron-deplete media and the murine lung. Yet, past studies failed to identify a role for the rhizoferrin biosynthetic gene (lbtA) in L. pneumophila infection of host cells, suggesting the siderophore's importance was solely linked to extracellular survival. To test the possibility that rhizoferrin's relevance to intracellular infection was missed due to functional redundancy with the ferrous iron transport (FeoB) pathway, we characterized a new mutant lacking both lbtA and feoB. This mutant was highly impaired for growth on bacteriological media that were only modestly depleted of iron, confirming that rhizoferrin-mediated ferric iron uptake and FeoB-mediated ferrous iron uptake are critical for iron acquisition. The lbtA feoB mutant, but not its lbtA-containing complement, was also highly defective for biofilm formation on plastic surfaces, demonstrating a new role for the L. pneumophila siderophore in extracellular survival. Finally, the lbtA feoB mutant, but not its complement containing lbtA, proved to be greatly impaired for growth in Acanthamoeba castellanii, Vermamoeba vermiformis, and human U937 cell macrophages, revealing that rhizoferrin does promote intracellular infection by L. pneumophila. Moreover, the application of purified rhizoferrin triggered cytokine production from the U937 cells. Rhizoferrin-associated genes were fully conserved across the many sequenced strains of L. pneumophila examined but were variably present among strains from the other species of Legionella. Outside of Legionella, the closest match to the L. pneumophila rhizoferrin genes was in Aquicella siphonis, another facultative intracellular parasite of amoebae.


Assuntos
Amoeba , Legionella pneumophila , Animais , Camundongos , Humanos , Legionella pneumophila/genética , Legionella pneumophila/metabolismo , Sideróforos/metabolismo , Amoeba/metabolismo , Células U937 , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Ferro/metabolismo , Macrófagos/microbiologia , Biofilmes
7.
Bioorg Med Chem ; 95: 117490, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37862936

RESUMO

Thirty-nine aryl azoles, thirteen triazoles and twenty-seven tetrazoles, have been synthetized and biologically evaluated to determine their activity as tumor microenvironment disruptors. Antiproliferative studies have been performed on tumor cell lines HT-29, A-549 and MCF-7 and on non-tumor cell line HEK-293. It has been studied in HT-29 the expression levels of biological targets which are involved in tumor microenvironment processes, such as PD-L1, CD-47, c-Myc and VEGFR-2. In addition, antiproliferative activity was evaluated when HT-29 were co-cultured with THP-1 monocytes and the secretion levels of IL-6 were also determined in these co-cultures. The angiogenesis effect of some selected compounds on HMEC-1 was also evaluated as well as their action against vasculogenic mimicry on HEK-293. Compounds bearing an amino group in the phenyl ring and a halogen atom in the benzyl ring showed promising results as tumor microenvironment disrupting agents. The most outstanding compound decrease dramatically the population of HT-29 cells when co-cultured with THP-1 monocytes and the levels of IL-6 secreted, as well as it showed moderate effects over PD-L1, CD-47 and c-Myc.


Assuntos
Azóis , Antígeno B7-H1 , Humanos , Microambiente Tumoral , Células HEK293 , Interleucina-6 , Linhagem Celular Tumoral
8.
Eur J Nutr ; 62(4): 1783-1794, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36840816

RESUMO

INTRODUCTION: Although acute caffeine intake seems to improve muscular strength-power-endurance performance, there is scarce evidence evaluating upper vs lower-body exercises at different loads. Thus, this study aimed to examine the effects of acute caffeine intake on upper and lower-body muscular strength, power and endurance performance at different loads. METHODS: Twenty resistance-trained athletes (male/female: 10/10; age: 23 ± 4 years; body mass: 70.6 ± 15.1) participated in a double-blind, placebo-controlled, cross-over and randomized study. Participants were provided with either 3 mg/kg of body mass of caffeine or maltodextrin (placebo). Sixty minutes after ingestion, they performed muscular strength and power assessment for bench press and back squat exercise at 25%, 50%, 75% and 90% 1-repetition-maximum (1RM), performing 3, 2, 1 and 1 repetitions respectively, followed by muscular endurance assessment for both exercises at 65% and 85% 1RM performing until task failure. Isometric handgrip, isometric mid-thigh pull and vertical jump tests were also performed. RESULTS: In muscular strength and power, compared to placebo, caffeine improved mean velocity (P = 0.045; pη2 = 0.101), mean power (P = 0.049; pη2 = 0.189) and rate of force development (RFD, P = 0.032; pη2 = 0.216), particularly in back squat exercise at 75% and 90% 1RM where mean velocity increased by 5-7% (P = 0.48-0.038; g = 0.348-1.413), mean power by 6-8% (P = 0.050-0.032; g = 0.547-0.818) and RFD by 17-97% (P = 0.042-0.046; g = 1.436-1.196). No differences were found in bench press exercise. In muscular endurance, caffeine improved the number of repetitions in all exercises and loads (P = 0.003; pη2 = 0.206), but only in back squat exercise at 85% 1RM, caffeine increased mean and peak velocity (8-9%, P = 0.006-0.004; g = 2.029-2.075), mean and peak power (10-13%, P = 0.006-0.003; g = 0.888-1.151) and force peak (3%, P = 0.009; g = 0.247). CONCLUSIONS: Acute caffeine intake (3 mg/kg) improved muscular strength, power and endurance performance, revealing a more pronounced effect at high-loads (≥ 75% 1RM) and in lower-body (back squat) than in upper-body exercise (bench press) according to muscle group size.


Assuntos
Substâncias para Melhoria do Desempenho , Treinamento Resistido , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Cafeína , Substâncias para Melhoria do Desempenho/farmacologia , Força da Mão , Força Muscular , Músculos , Resistência Física , Método Duplo-Cego
9.
Eur J Nutr ; 62(3): 1123-1130, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36401662

RESUMO

PURPOSE: Beetroot juice is a dietary supplement that contains high levels of inorganic nitrate (NO3-) and that its intake has proven effective at increasing blood nitric oxide (NO) concentrations improving endurance performance. However, the effect of this supplement in team sport performance, especially in female athletes, has been barely studied. This study aimed to compare the acute effects of beetroot juice supplementation on neuromuscular performance and match-play demands in elite female field hockey players. METHODS: Eleven elite female hockey players (22.8 ± 5.1 years) belonging to a bronze team medal in Eurohockey Club Champions Cup participated in this study. Participants were randomly divided into two groups undergoing a test battery with beetroot juice (70 mL, 6.4 mmol NO3-) or placebo (70 mL, 0.04 mmol NO3-) in two different days with one week between protocols. The neuromuscular test battery consisted of a countermovement jump, isometric handgrip strength (i.e., dominant hand), 20 m-sprint and repeated sprint ability test (RSA). Afterward, a simulated hockey match play (2 × 12.5 min) was performed and recorded by Global Positioning System (GPS). RESULTS: No statistically significant improvements were observed in any physical parameters analysed comparing beetroot juice compared to placebo ingestion, countermovement jump (p = 0.776, ES = 0.16), isometric handgrip strength (p = 0.829; ES = - 0.08), 20 m sprint test (p = 0.227; ES = - 0.23), mean repeated sprint ability (p = 0.955, ES = 0.03) and in any physical match demands measured by GPS (p = 0.243-1.000; ES = 0.02-0.47). CONCLUSION: Acute beetroot juice supplementation did not produce any statistically significant improvement in neuromuscular performance or match-play demands in elite female field hockey players. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov with the following ID: NCT05209139. The study was retrospectively registered by 26 January 2022.


Assuntos
Desempenho Atlético , Beta vulgaris , Hóquei , Humanos , Feminino , Força da Mão , Sucos de Frutas e Vegetais , Nitratos , Suplementos Nutricionais , Antioxidantes , Método Duplo-Cego , Ingestão de Alimentos
10.
Sensors (Basel) ; 23(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36772764

RESUMO

Adulterations of olive oil are performed by adding seed oils to this high-quality product, which are cheaper than olive oils. Food safety controls have been established by the European Union to avoid these episodes. Most of these methodologies require expensive equipment, time-consuming procedures, and expert personnel to execute. Near-infrared spectroscopy (NIRS) technology has many applications in the food processing industry. It analyzes food safety and quality parameters along the food chain. Using principal component analysis (PCA), the differences and similarities between olive oil and seed oils (sesame, sunflower, and flax oil) have been evaluated. To quantify the percentage of adulterated seed oil in olive oils, partial least squares (PLS) have been employed. A total of 96 samples of olive oil adulterated with seed oils were prepared. These samples were used to build a spectra library covering various mixtures containing seed oils and olive oil contents. Eighteen chemometric models were developed by combining the first and second derivatives with Standard Normal Variable (SNV) for scatter correction to classify and quantify seed oil adulteration and percentage. The results obtained for all seed oils show excellent coefficients of determination for calibration higher than 0.80. Because the instrumental aspects are not generally sufficiently addressed in the articles, we include a specific section on some key aspects of developing a high-performance and cost-effective NIR spectroscopy solution for fraud detection in olive oil. First, spectroscopy architectures are introduced, especially the Texas Instruments Digital Light Processing (DLP) technology for spectroscopy that has been used in this work. These results demonstrate that the portable prototype can be used as an effective tool to detect food fraud in liquid samples.


Assuntos
Óleos de Plantas , Espectroscopia de Luz Próxima ao Infravermelho , Azeite de Oliva/análise , Óleos de Plantas/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Contaminação de Alimentos/análise , Fraude/prevenção & controle , Óleo de Girassol
11.
Gastroenterol Hepatol ; 46(5): 329-335, 2023 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36243252

RESUMO

BACKGROUND AND AIM: In inflammatory bowel disease (IBD), diet can be perceived as a trigger for relapses or clinical worsening, dietary modifications are frequent and not derived from professional advice. The aim of this study was to evaluate the perception of the need for dietary advice in patients with IBD, to know the dietary modifications adopted and, it's effect on IBD. METHODS: An anonymous structured questionnaire with a visual analog scale (0-10) was distributed to consecutive outpatients from our IBD unit. RESULTS: A total of 124 complete the questionnaire (54% ulcerative colitis, 46% Crohn's disease). Mean age was 47±12 years. Dietary advice provided in the clinic was assessed with a median score of 7 (IIC, 4.50-9.00). 40% sought external dietary advice, often during the first year after diagnosis (70%). The most frequent dietary recommendations from an external professional were: dairy free diet (29%), low fat (27%), gluten free (23%), and low fiber (21%). Dietary advice from external source was assessed with a median score of 7.50 (IIC, 5.50-9.50), improving digestive symptoms in 73% of cases. Regarding dietary modifications, 61% excluded some foods (57% permanently) and 11% fasted on their own decision. CONCLUSIONS: IBD patient show a clear need for dietary advice, especially at the time of IBD diagnosis. Early specific and in-depth dietary information would increase patient satisfaction and could prevent the adoption of unjustified exclusion diets.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Adulto , Pessoa de Meia-Idade , Dieta , Percepção
12.
Rev Gastroenterol Peru ; 43(4): 309-318, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-38228296

RESUMO

Colonoscopy screening is an effective method to prevent colon cancer through the detection of polyps on which colon cancer develops in a higher percentage; however, the detection of these lesions varies in the different segments of the colon and the detection rate of them in the right colon is usually lower. OBJECTIVE: The objective of this study is to evaluate whether double endoscopic revision of the right colon during colonoscopy is a mechanism to improve its performance in terms of polyp detection rate (TDP) and adenoma detection rate (ADR). MATERIALS AND METHODS: Systematic review and meta-analysis of the literature including randomized clinical trials that evaluated repeat right-sight examination by colonoscopy compared to standard view to improve detection of polyps and adenomas. The protocol for this decision was published in PROSPERO under the code CRD42022356509. RESULTS: Five studies involving 2729 participants were included. Polyp detection was reported in 585/1197 patients (48.87%) after the second review, compared with 537/1206 (44.52%) of patients who received a single examination (p< 0.05), for a combined RR of 1.09 (95% CI: 0.97-1.23) (I2 was 44%). Detection of adenomas was reported in 830/1513 patients (54.75%) after the second review, compared with 779/1509 (51.62%) of patients who received a single examination (p < 0.05), for a combined RR of 1.06 (95% CI: 1.00-1.13) (I2 was 0%). CONCLUSION: Second examination of the right colon by colonoscopy may have a modest improvement in the detection of polyps and adenomas.


Assuntos
Adenoma , Neoplasias do Colo , Pólipos do Colo , Humanos , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Colonoscopia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Adenoma/diagnóstico , Adenoma/patologia
13.
J Virol ; 95(13): e0026621, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110264

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. While previous studies have shown that several SARS-CoV-2 proteins can antagonize the interferon (IFN) response, some of the mechanisms by which they do so are not well understood. In this study, we describe two novel mechanisms by which SARS-CoV-2 blocks the IFN pathway. Type I IFNs and IFN-stimulated genes (ISGs) were poorly induced during SARS-CoV-2 infection, and once infection was established, cells were highly resistant to ectopic induction of IFNs and ISGs. Levels of two key IFN signaling pathway components, Tyk2 and STAT2, were significantly lower in SARS-CoV-2-infected cells. Expression of nonstructural protein 1 (NSP1) or nucleocapsid in the absence of other viral proteins was sufficient to block IFN induction, but only NSP1 was able to inhibit IFN signaling. Mapping studies suggest that NSP1 prevents IFN induction in part by blocking IRF3 phosphorylation. In addition, NSP1-induced depletion of Tyk2 and STAT2 dampened ISG induction. Together, our data provide new insights into how SARS-CoV-2 successfully evades the IFN system to establish infection. IMPORTANCE SARS-CoV-2 is the causative agent of COVID-19, a serious disease that can have a myriad of symptoms from loss of taste and smell to pneumonia and hypercoagulation. The rapid spread of SARS-CoV-2 can be attributed in part to asymptomatic transmission, where infected individuals shed large amounts of virus before the onset of disease. This is likely due to the ability of SARS-CoV-2 to effectively suppress the innate immune system, including the IFN response. Indeed, we show that the IFN response is efficiently blocked during SARS-CoV-2 infection, a process that is mediated in large part by nonstructural protein 1 and nucleocapsid. Our study provides new insights on how SARS-CoV-2 evades the IFN response to successfully establish infection. These findings should be considered for the development and administration of therapeutics against SARS-CoV-2.


Assuntos
Interferon Tipo I/antagonistas & inibidores , SARS-CoV-2/metabolismo , Transdução de Sinais , Proteínas não Estruturais Virais/metabolismo , Animais , COVID-19/imunologia , COVID-19/virologia , Chlorocebus aethiops , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Células HEK293 , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Fosfoproteínas/metabolismo , SARS-CoV-2/patogenicidade , Fator de Transcrição STAT2/metabolismo , TYK2 Quinase/metabolismo , Células Vero
14.
J Vasc Surg ; 75(3): 1063-1072, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34562570

RESUMO

OBJECTIVE: We sought to detail the process of establishing a surgical aortic telehealth program and report the outcomes of a 5-year experience. METHODS: A telehealth program was established between two regional Veterans Affairs hospitals, one of which was without a comprehensive aortic surgical program, until such a program was established at the referring institution. A retrospective review was performed of all patients who underwent aortic surgery from 2014 to 2019. The operative data, demographics, perioperative complications, and follow-up data were reviewed. RESULTS: From 2014 to 2019, 109 patients underwent aortic surgery for occlusive and aneurysmal disease. Preoperative evaluation and postoperative follow-up were done remotely via telehealth. The median age of the patients was 68 years, 107 were men (98.2%), 28 (25.7%) underwent open aortic repair, and 81 (74.3%) underwent endovascular repair. Of the 109 patients, 101 (92.7%) had a median follow-up of 24.3 months, 5 (4.6%) were lost to follow-up or were noncompliant, 2 (1.8%) were noncompliant with their follow-up imaging studies but responded to telephone interviews, and 1 (0.9%) moved to another state. At the 30-day follow-up, eight patients (7.3%) required readmission. Four complications were managed locally, and four patients (3.6%) required transfer back to the operative hospital for additional care. CONCLUSIONS: Telehealth is a great tool to provide perioperative care and long-term follow-up for patients with aortic pathologies in remote locations. Most postoperative care and complications can be managed remotely, and patient compliance for long-term follow-up is high.


Assuntos
Doenças da Aorta/cirurgia , Prestação Integrada de Cuidados de Saúde/organização & administração , Procedimentos Endovasculares , Avaliação de Processos e Resultados em Cuidados de Saúde/organização & administração , Telemedicina/organização & administração , Procedimentos Cirúrgicos Vasculares/organização & administração , Comunicação por Videoconferência/organização & administração , Idoso , Doenças da Aorta/diagnóstico por imagem , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Readmissão do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Avaliação de Programas e Projetos de Saúde , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , United States Department of Veterans Affairs , Procedimentos Cirúrgicos Vasculares/efeitos adversos
15.
Mol Psychiatry ; 26(7): 3134-3151, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33046833

RESUMO

Epigenetic mechanisms, like those involving DNA methylation, are thought to mediate the relationship between chronic cocaine dependence and molecular changes in addiction-related neurocircuitry, but have been understudied in human brain. We initially used reduced representation bisulfite sequencing (RRBS) to generate a methylome-wide profile of cocaine dependence in human post-mortem caudate tissue. We focused on the Iroquois Homeobox A (IRXA) gene cluster, where hypomethylation in exon 3 of IRX2 in neuronal nuclei was associated with cocaine dependence. We replicated this finding in an independent cohort and found similar results in the dorsal striatum from cocaine self-administering mice. Using epigenome editing and 3C assays, we demonstrated a causal relationship between methylation within the IRX2 gene body, CTCF protein binding, three-dimensional (3D) chromatin interaction, and gene expression. Together, these findings suggest that cocaine-related hypomethylation of IRX2 contributes to the development and maintenance of cocaine dependence through alterations in 3D chromatin structure in the caudate nucleus.


Assuntos
Cromatina , Transtornos Relacionados ao Uso de Cocaína , Metilação de DNA , Proteínas de Homeodomínio/genética , Família Multigênica , Neurônios , Animais , Cocaína , Transtornos Relacionados ao Uso de Cocaína/genética , Camundongos
16.
Org Biomol Chem ; 20(2): 396-409, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34904608

RESUMO

A straightforward synthesis of indolizines and pyrrolo[1,2-a]pyrazines was performed through a cascade condensation/cyclization/aromatization reaction of substituted 2-formyl-N-propargylpyrroles with active methylene compounds such as nitromethane, alkyl malonates, methyl cyanoacetate and malononitrile. Under basic conditions, the reaction proceeded satisfactorily to provide the corresponding 6,7-disubstituted indolizines. The condensation of the pyrrolic analogues with ammonium acetate gave rise to pyrrolo[1,2-a]pyrazines in high yields. N-Allenyl-2-formylpyrroles behaved as more reactive substrates than 2-formyl-N-propargylpyrroles, furnishing the expected indolizines in higher yields. Hence, an allenyl-containing intermediate was probably generated as the reactive species in the reaction mechanism of some N-propargyl pyrroles prior to the cyclization reaction.

17.
Neuropediatrics ; 53(5): 376-380, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35512844

RESUMO

Mechanical thrombectomy (MT) in pediatric stroke is supported by studies in adults, but there is controversy regarding younger patients. The main growth of intracranial vessels occurs up to 2 years when there can be more difficulties in MT.Description of the MT performed in a 2-month-old patient-the youngest infant published to date. We also review the literature on MT for stroke in infants.A 2-month-old patient presented with an awakening stroke secondary to an occlusion of the M1 segment of the left middle cerebral artery. A successful MT was performed with an aspiration device without clinically significant complications. An etiological study was completed, and neuroimaging showed focal cerebral arteriopathy. The 3-month outcome was excellent: the pediatric modified Rankin score was 0.Including this case, MT for acute stroke has been reported in only 10 infants. MT was successful in 90%, mostly using adult conventional stent retrievers. There were complications only in patients with mechanical circulatory support (MCS) devices; three patients died due to hemorrhagic transformation after MT and one patient died due to recurrent ischemic stroke.MT seems effective and safe in infants similarly to other pediatric ages. In children under 2 years of age, the presence of comorbidities requiring MCS devices is the main factor underlying poor prognosis.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Adulto , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Criança , Humanos , Lactente , Neuroimagem , Estudos Retrospectivos , Stents , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do Tratamento
18.
Epilepsy Behav ; 134: 108808, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35809503

RESUMO

BACKGROUND: We aimed to assess the risk of developing new-onset seizures or seizure decompensations in people with epilepsy (PWE) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. METHODS: A retrospective observational study in a tertiary hospital was conducted. Clinical records of all patients attended because of seizures or epilepsy at outpatient clinics, emergency department, or admitted to our hospital from January to December 2021 were reviewed, including patients older than 16 years who received some dose of coronavirus disease 2019 (COVID-19) vaccines. RESULTS: A total of 418 vaccinated PWE were analyzed: 6.2% presented an increase in seizure frequency and 1% reported different seizure types during the next month after vaccination. However, 61.5% had another possible cause for this decompensation. Having monthly seizures (1-3/month) was the only associated risk factor (OR 4.9, p < 0.001) while being seizure free > 1 year had a protective role (OR 0.36, p = 0.019). Patients with epileptic encephalopathies or a history of COVID-19 infection were not at increased risk of seizure decompensation. Besides this, 15 patients presented new-onset seizures within the first month post-vaccination, mean time from vaccination 15 ±â€¯8 days, 67% after the second dose. Again, 53.3% had another possible trigger for seizures. Eight debuted with status epilepticus or cluster of seizures. CONCLUSIONS: A small proportion of PWE (6.2%) had an increase in seizure frequency after COVID-19 vaccination and 15 patients had new-onset seizures during the first month after vaccination, though another reason for seizure exacerbation was identified in 61.5% and 53.3%, respectively. Severe acute respiratory syndrome COVID-19 vaccines appear to have little impact on the generation or decompensation of seizures.


Assuntos
COVID-19 , Epilepsia , Vacinas contra COVID-19 , Humanos , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2 , Convulsões , Vacinação
19.
BMC Cardiovasc Disord ; 22(1): 514, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460985

RESUMO

BACKGROUND: Cardiac myofibrillary dysfunction, which can be measure by echocardiographical strain value, represents an early subclinical manifestation of heart failure. Epicardial Adipose tissue (EAT) is related to low degree inflammation and oxidative damage in the adjacent tissue. AIM: To explore whether EAT affects early myocardial dysfunction, as assessed strain values. METHODS: Case-Control design. Patients lacking clinical significant heart failure, thyroid or renal disease or malignant abnormalities were included. Clinical-demographic and biochemical data were collected. EAT and myofibril deformation were measured by echocardiography. RESULTS: A total of 71 patients were analyzed, and further subdivided according to type 2 Diabetes Mellitus (t2DM). Higher strain value (higher than -22.4%cut-off value) was associated with male sex and higher anthropometric and metabolic risk measures; particularly those with t2DM. Higher EAT was also associated higher strain value (AUC = 0.92 ± 0.06, p = 0.004), and further correlation was evidenced (rho = 0.488, p < 0.001), with significant influence of t2DM. CONCLUSION: EAT was related to strain value, suggesting the influence of cardiac adipose tissue on the deformability of cardiac myofibril, with a more significant effect in the population with t2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Estudos de Casos e Controles , Tecido Adiposo/diagnóstico por imagem , Coração
20.
Ann Vasc Surg ; 82: 30-40, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34954038

RESUMO

BACKGROUND: Data on management of traumatic lower extreity arterial injuries comes largely from military experience and involves few civilian centers. This study reports on the experience of an urban trauma center and factors associated with limb loss. METHODS: A retrospective review of lower extremity arterial injuries between 2013 and 2020 at an academic urban level 1 trauma center was completed. Patients with lower extremity revascularization were included in the final data analysis. Demographics, clinical variables, operative details, type of revascularization, as well as 30-day morbidity and postoperative outcomes were analyzed. The primary outcome of interest was 30-day limb loss. Secondary outcomes included postoperative complications and functional outcomes. RESULTS: Seventy-five patients were included in our analysis. Sixty-nine were male (92%), mean age 33 ± 15 years, 50 patients had penetrating trauma (67%), mean injury severity score was 15 ± 9. Thirty-day limb loss was reported in 8 (11%). Factors associated with limb loss included female sex (P = 0.001), high body mass index (P = 0.001), blunt injury (P = 0.001), associated fractures (P = 0.005), significant soft tissue injury (P = 0.007), delayed repair after shunt placement (P = 0.003), bypass revascularization (P = 0.001), initial revascularization failure (P = 0.019), and wound complications (P < 0.001). Fifty-five patients had at least one return to the operating room (ROR), including 24 patients (32%) for complications related to their revascularization. These included delayed compartment syndrome (n = 7), revascularization failure (n = 9), bleeding (n = 3), and vascular surgical wound complications (n = 5). Mean length of hospital stay (LOS) for the cohort was 24 ± 20 days with 3 ± 3 ROR, in contrast patients who ultimately required amputation had LOS of 57 ± 21 days with 8 ± 4 ROR. Fifty-seven patients (76%) followed in clinic for a median 36 [14-110] days, with only 32 (43%) at >30 days. Twenty-three reported ambulation without assistance, 9 neuromotor deficit including 1 patient that had delayed amputation. CONCLUSION: Patients with blunt trauma and associated fracture and/or extensive soft tissue injury are at risk of limb loss. These injuries are often associated with postoperative wound complications, requiring aggressive soft tissue care that substantially increases ROR and LOS; Expectations for limb salvage in these patients should be tempered when the other associated factors with limb loss mentioned above are also present. When limb salvage is achieved, regaining full limb function remains a challenge.


Assuntos
Lesões dos Tecidos Moles , Lesões do Sistema Vascular , Ferimentos não Penetrantes , Adolescente , Adulto , Amputação Cirúrgica/efeitos adversos , Feminino , Humanos , Salvamento de Membro/efeitos adversos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Lesões dos Tecidos Moles/complicações , Lesões dos Tecidos Moles/cirurgia , Centros de Traumatologia , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia , Ferimentos não Penetrantes/cirurgia , Adulto Jovem
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