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1.
Eur J Neurol ; 31(5): e16228, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38375947

RESUMO

BACKGROUND AND PURPOSE: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce. METHODS: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed. RESULTS: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38-0.92) to 0.03 (95% CI 0.02-0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70-2.48) to 0.08 (95% CI 0.03-0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30-3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events. CONCLUSION: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Criança , Humanos , Rituximab/efeitos adversos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Estudos Retrospectivos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva
2.
Genome Res ; 30(12): 1766-1780, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33127752

RESUMO

Alternative splicing plays a major role in shaping tissue-specific transcriptomes. Among the broad tissue types present in metazoans, the central nervous system contains some of the highest levels of alternative splicing. Although many documented examples of splicing differences between broad tissue types exist, there remains much to be understood about the splicing factors and the cis sequence elements controlling tissue and neuron subtype-specific splicing patterns. By using translating ribosome affinity purification coupled with deep-sequencing (TRAP-seq) in Caenorhabditis elegans, we have obtained high coverage profiles of ribosome-associated mRNA for three broad tissue classes (nervous system, muscle, and intestine) and two neuronal subtypes (dopaminergic and serotonergic neurons). We have identified hundreds of splice junctions that exhibit distinct splicing patterns between tissue types or within the nervous system. Alternative splicing events differentially regulated between tissues are more often frame-preserving, are more highly conserved across Caenorhabditis species, and are enriched in specific cis regulatory motifs, when compared with other types of exons. By using this information, we have identified a likely mechanism of splicing repression by the RNA-binding protein UNC-75/CELF via interactions with cis elements that overlap a 5' splice site. Alternatively spliced exons also overlap more frequently with intrinsically disordered peptide regions than constitutive exons. Moreover, regulated exons are often shorter than constitutive exons but are flanked by longer intron sequences. Among these tissue-regulated exons are several highly conserved microexons <27 nt in length. Collectively, our results indicate a rich layer of tissue-specific gene regulation at the level of alternative splicing in C. elegans that parallels the evolutionary forces and constraints observed across metazoa.


Assuntos
Processamento Alternativo , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Perfilação da Expressão Gênica/métodos , Proteínas de Ligação a RNA/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Éxons , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Intestinos/química , Músculo Esquelético/química , Sistema Nervoso/química , Especificidade de Órgãos , Análise de Sequência de RNA , Distribuição Tecidual
3.
Ann Neurol ; 91(3): 342-352, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35067959

RESUMO

OBJECTIVE: The study was undertaken to assess the impact of B cell depletion on humoral and cellular immune responses to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccination in patients with various neuroimmunologic disorders on anti-CD20 therapy. This included an analysis of the T cell vaccine response to the SARS-CoV-2 Delta variant. METHODS: We investigated prospectively humoral and cellular responses to SARS-CoV-2 mRNA vaccination in 82 patients with neuroimmunologic disorders on anti-CD20 therapy and 82 age- and sex-matched healthy controls. For quantification of antibodies, the Elecsys anti-SARS-CoV-2 viral spike (S) immunoassay against the receptor-binding domain (RBD) was used. IFN-gamma enzyme-linked immunosorbent spot assays were performed to assess T cell responses against the SARS-CoV-2 Wuhan strain and the Delta variant. RESULTS: SARS-CoV-2-specific antibodies were found less frequently in patients (70% [57/82]) compared with controls (82/82 [100%], p < 0.001). In patients without detectable B cells (<1 B cell/mcl), seroconversion rates and antibody levels were lower compared to nondepleted (≥1 B cell/mcl) patients (p < 0.001). B cell levels ≥1 cell/mcl were sufficient to induce seroconversion in our cohort of anti-CD20 treated patients. In contrast to the antibody response, the T-cell response against the Wuhan strain and the Delta variant was more pronounced in frequency (p < 0.05) and magnitude (p < 0.01) in B-cell depleted compared to nondepleted patients. INTERPRETATION: Antibody responses to SARS-CoV-2 mRNA vaccinnation can be attained in patients on anti-CD20 therapy by the onset of B cell repopulation. In the absence of B cells, a strong T cell response is generated which may help to protect against severe coronavirus disease 2019 (COVID-19) in this high-risk population. ANN NEUROL 2022;91:342-352.


Assuntos
Doenças Autoimunes do Sistema Nervoso/imunologia , Linfócitos B/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , SARS-CoV-2/imunologia , Adulto , Doenças Autoimunes do Sistema Nervoso/sangue , Doenças Autoimunes do Sistema Nervoso/epidemiologia , Linfócitos B/metabolismo , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimunomodulação/imunologia , Estudos Prospectivos , SARS-CoV-2/metabolismo
4.
Infection ; 51(6): 1749-1758, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37462895

RESUMO

PURPOSE: This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy. METHODS: This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia. RESULTS: Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups. CONCLUSIONS: Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.


Assuntos
Bacteriemia , Infecções por Escherichia coli , Quinolonas , Adulto , Humanos , Sulbactam/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Piperacilina/farmacologia , Piperacilina/uso terapêutico , Estudos de Coortes , Escherichia coli , Estudos Retrospectivos , Ácido Penicilânico/farmacologia , Ácido Penicilânico/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Cefalosporinas , Bacteriemia/tratamento farmacológico
5.
Ecol Modell ; 481: 110374, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37396396

RESUMO

[This corrects the article DOI: 10.1016/j.ecolmodel.2021.109690.].

6.
Clin Gastroenterol Hepatol ; 20(9): 2145-2147.e2, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35487452

RESUMO

Patients suffering from autoimmune hepatitis, a chronic immune-mediated liver disease with an incidence of 0.9 to 2 per 100,000 population per year in Europe, are considered to have a particularly increased risk for coronavirus disease 2019 (Covid-19)-associated hospitalization and death.1,2 Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination provides an essential tool to reduce morbidity and mortality in this cohort. However, a large multicenter study in China has shown a lower immunogenic response to inactivated whole-virion SARS-CoV-2 vaccines of chronic liver disease patients in comparison with the healthy population.3 Furthermore, reports from inflammatory bowel diseases or rheumatic disorders showed a reduced serologic response in patients taking glucocorticoids or thiopurine.4,5 The decrease in vaccine-induced antibodies over time, as well as the emergence of variants of concern, led to the recommendation of an additional vaccination in immunocompromised patients.


Assuntos
COVID-19 , Hepatite Autoimune , Vacinas Virais , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Vacinação
7.
Mol Syst Biol ; 17(6): e9600, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34169647

RESUMO

Transposable elements (TEs) are widespread across eukaryotic genomes, yet their content varies widely between different species. Factors shaping the diversity of TEs are poorly understood. Understanding the evolution of TEs is difficult because their sequences diversify rapidly and TEs are often transferred through non-conventional means such as horizontal gene transfer. We developed a method to track TE evolution using network analysis to visualise TE sequence and TE content across different genomes. We illustrate our method by first using a monopartite network to study the sequence evolution of Tc1/mariner elements across focal species. We identify a connection between two subfamilies associated with convergent acquisition of a domain from a protein-coding gene. Second, we use a bipartite network to study how TE content across species is shaped by epigenetic silencing mechanisms. We show that the presence of Piwi-interacting RNAs is associated with differences in network topology after controlling for phylogenetic effects. Together, our method demonstrates how a network-based approach can identify hitherto unknown properties of TE evolution across species.


Assuntos
Elementos de DNA Transponíveis , Evolução Molecular , Elementos de DNA Transponíveis/genética , Filogenia , RNA Interferente Pequeno
8.
Nephrol Dial Transplant ; 37(2): 335-348, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33295624

RESUMO

BACKGROUND: Sex-specific differences in nephrolithiasis with respect to both distribution of prevalence and stone composition are widely described and may be influenced by sex hormones. METHODS: We conducted a cross-sectional analysis of the relationship between 24-h urinary sex hormone metabolites measured by gas chromatography-mass spectrometry with urinary calcium, oxalate and citrate excretion in a cohort of 628 kidney stone formers from a tertiary care hospital in Switzerland, taking demographic characteristics, kidney function and dietary factors into account. RESULTS: We observed a positive association of urinary calcium with urinary testosterone and 17ß-oestradiol. Positive associations of urinary calcium with dehydroepiandrosterone (DHEA), 5α-DH-testosterone, aetiocholanolone, androsterone and oestriol were modified by net gastrointestinal alkali absorption or urinary sulphate excretion. As the only sex hormone, DHEA was inversely associated with urinary oxalate excretion in adjusted analyses. Urinary citrate correlated positively with urinary testosterone. Associations of urinary citrate with urinary androsterone, 17ß-oestradiol and oestriol were modified by urinary sulphate or sodium or by sex. CONCLUSIONS: Urinary androgens and oestrogens are significantly associated with urinary calcium and citrate excretion and associations are modified in part by diet. Our data furthermore reveal DHEA as a novel factor associated with urinary oxalate excretion in humans.


Assuntos
Cálcio , Cálculos Renais , Cálcio/urina , Citratos/urina , Ácido Cítrico , Estudos Transversais , Feminino , Hormônios Esteroides Gonadais , Humanos , Cálculos Renais/etiologia , Cálculos Renais/urina , Masculino , Oxalatos
9.
Ecol Modell ; 459: 109690, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34732971

RESUMO

The ecological importance of mixoplankton within marine protist communities is slowly being recognized. However, most aquatic ecosystem models do not include formulations to model a complete protist community consisting of phytoplankton, protozooplankton and mixoplankton. We introduce PROTIST, a new module for the aquatic ecosystem modelling software Delft3D-WAQ that can model a protist community consisting of two types of phytoplankton (diatoms and green algae), two types of mixoplankton (constitutive mixoplankton and non-constitutive mixoplankton) and protozooplankton. We employed PROTIST to further explore the hypothesis that the biogeochemical gradient of inorganic nutrient and suspended sediment concentrations drives the observed occurrence of constitutive mixoplankton in the Dutch Southern North Sea. To explore this hypothesis, we used 11 1D-vertical aquatic ecosystem models that mimic the abiotic conditions of 11 routine monitoring locations in the Dutch Southern North Sea. Our models result in plausible trophic compositions across the biogeochemical gradient as compared to in-situ data. A sensitivity analysis showed that the dissolved inorganic phosphate and silica concentrations drive the occurrence of constitutive mixoplankton in the Dutch Southern North Sea.

10.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070905

RESUMO

BACKGROUND: The interleukin-1-receptor antagonist IL1RA (encoded by the IL1RN gene) is a potent competitive antagonist to interleukin-1 (IL1) and thereby is mainly involved in the regulation of inflammation. Previous data indicated a role of IL1RA in muscle-invasive urothelial carcinoma of the bladder (UCB) as well as an IL1-dependent decrease in tissue barrier function, potentially contributing to cancer cell invasion. OBJECTIVE: Based on these observations, here we investigated the potential roles of IL1RA, IL1A, and IL1B in bladder cancer cell invasion in vitro. METHODS: Cell culture, real-time impedance sensing, invasion assays (Boyden chamber, pig bladder model), qPCR, Western blot, ELISA, gene overexpression. RESULTS: We observed a loss of IL1RA expression in invasive, high-grade bladder cancer cell lines T24, UMUC-3, and HT1197 while IL1RA expression was readily detectable in the immortalized UROtsa cells, the non-invasive bladder cancer cell line RT4, and in benign patient urothelium. Thus, we modified the invasive human bladder cancer cell line T24 to ectopically express IL1RA, and measured changes in cell migration/invasion using the xCELLigence Real-Time-Cell-Analysis (RTCA) system and the Boyden chamber assay. The real-time observation data showed a significant decrease of cell migration and invasion in T24 cells overexpressing IL1RA (T24-IL1RA), compared to cells harboring an empty vector (T24-EV). Concurrently, tumor cytokines, e.g., IL1B, attenuated the vascular endothelial barrier, which resulted in a reduction of the Cell Index (CI), an impedance-based dimensionless unit. This reduction could be reverted by the simultaneous incubation with IL1RA. Moreover, we used an ex vivo porcine organ culture system to evaluate cell invasion capacity and showed that T24-IL1RA cells showed significantly less invasive capacity compared to parental T24 cells or T24-EV. CONCLUSIONS: Taken together, our results indicate an inverse correlation between IL1RA expression and tumor cell invasive capacity and migration, suggesting that IL1RA plays a role in bladder carcinogenesis, while the exact mechanisms by which IL1RA influences tumor cells migration/invasion remain to be clarified in future studies. Furthermore, we confirmed that real-time impedance sensing and the porcine ex vivo organ culture methods are powerful tools to discover differences in cancer cell migration and invasion.


Assuntos
Movimento Celular/genética , Células Epiteliais/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Neoplasias da Bexiga Urinária/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células Epiteliais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Invasividade Neoplásica , Transdução de Sinais , Suínos , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
11.
Nephrol Dial Transplant ; 34(1): 129-137, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29939320

RESUMO

Background: Hypercalciuria is the most frequent metabolic disorder encountered in kidney stone formers (SF). Reduced renal phosphate reabsorption (i.e. renal phosphate leak) was proposed to be a driver of hypercalciuria in calcium SF. However, the phenotype of SF with renal phosphate leak remains poorly defined and the association of renal phosphate leak with stone history, stone composition and bone mineral density (BMD) has not been studied. Methods: To fill these knowledge gaps, we conducted a cross-sectional analysis in a cohort of 555 idiopathic calcareous SF. The ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR) was used to evaluate renal phosphate transport. Results: Multivariable regression analyses revealed a negative association of parathyroid hormone (PTH), a positive association of 25-hydroxy vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) but no association of fibroblast growth factor 23 (FGF23) with TmP/GFR. SF with low TmP/GFR had their first stone event at a younger age and were more likely to have a positive family history of kidney stones. In addition, urinary calcium excretion and prevalence of brushite stones were significantly higher in SF with low TmP/GFR. However, BMD, measured by dual-energy X-ray absorptiometry, was not associated with TmP/GFR in SF. Conclusions: Renal phosphate handling has a strong heritable component in SF and correlates with PTH, 25(OH)D and 1,25(OH)2D, but not with FGF23 levels. Furthermore, a low TmP/GFR (i.e. a renal phosphate leak) is associated with higher urinary calcium excretion and an increased prevalence of brushite stones.


Assuntos
Taxa de Filtração Glomerular , Hipofosfatemia Familiar/complicações , Cálculos Renais/etiologia , Fosfatos/metabolismo , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Cálculos Renais/metabolismo , Cálculos Renais/patologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/metabolismo , Fenótipo
13.
J Surg Oncol ; 118(1): 221-227, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30196538

RESUMO

BACKGROUND AND OBJECTIVES: Preoperative breast magnetic resonance imaging (B-MRI) staging in newly diagnosed breast cancer increases detection of synchronous contralateral findings, but may result in false-positive outcomes. This study objective was to identify women more likely of having mammographically occult, MRI detected contralateral breast cancer (CBC). METHODS: We performed a retrospective review of patients who had preoperative B-MRI prior to surgery from 2010 to 2015 and collected patient imaging and clinicopathologic data. Multivariate logistic regression was used to identify predictors of CBC. RESULTS: MRI resulted in contralateral findings in 201 of 1894 patients (10.6%). Overall 3.2% (60 of 1894) had synchronous CBC detected on B-MRI. The majority of CBCs (n = 60) were stage 0 or IA (85.0%), hormone receptor positive (94.9%), human epidermal growth factor receptor 2 (HER2/neu) negative (89.7%), and low/intermediate pathological grade (87.2%). Women more likely to have CBC were older (P < .001), had lobular index cancer (P = .03), and estrogen receptor (ER)+ (P = .027) or progesterone receptor (PR)+ (P = .002) tumors. On multivariate analysis (receiver operating characteristic curve area = 0.75), PR + status (P = .022), and older age (P = .004) were predictive of CBC. CONCLUSIONS: Preoperative MRI is most effective in detecting early stage, hormone receptor-positive CBC in older women.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética/métodos , Mastectomia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos
14.
Ann Plast Surg ; 78(5): 552-556, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27750269

RESUMO

BACKGROUND: The ethical practice of medicine has always been of utmost importance, and plastic surgery is no exception. The literature is devoid of information on the teaching of ethics and professionalism in plastic surgery. In light of this, a survey was sent to ascertain the status of ethics training in plastic surgery residencies. METHODS: A 21-question survey was sent from the American Council of Academic Plastic Surgeons meeting to 180 plastic surgery program directors and coordinators via email. Survey questions inquired about practice environment, number of residents, presence of a formal ethics training program, among others. Binary regression was used to determine if any relationships existed between categorical variables, and Poisson linear regression was used to assess relationships between continuous variables. Statistical significance was set at a P value of 0.05. RESULTS: A total of 104 members responded to the survey (58% response rate). Sixty-three percent were program directors, and most (89%) practiced in academic settings. Sixty-two percent in academics reported having a formal training program, and 60% in private practice reported having one. Only 40% of programs with fewer than 10 residents had ethics training, whereas 78% of programs with more than 20 residents did. The odds of having a training program were slightly higher (odds ratio, 1.1) with more residents (P = 0.17). CONCLUSIONS: Despite the lack of information in the literature, formal ethics and professionalism training does exist in many plastic surgery residencies, although barriers to implementation do exist. Plastic surgery leadership should be involved in the development of standardized curricula to help overcome these barriers.


Assuntos
Ética Médica/educação , Profissionalismo/educação , Profissionalismo/ética , Cirurgia Plástica/educação , Cirurgia Plástica/ética , Estudos Transversais , Educação de Pós-Graduação em Medicina , Humanos , Internato e Residência , Inquéritos e Questionários , Estados Unidos
15.
Biochemistry ; 55(10): 1433-40, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26885878

RESUMO

The copper enzyme nitrous oxide reductase catalyzes the two-electron reduction of nitrous oxide N2O to dinitrogen N2. Its maturation largely occurs in the periplasm and includes the insertion of at least one Ca²âº ion per monomer. Here we have investigated the role of this structural cation in recombinantly produced apo-N2OR from Shewanella denitrificans and have determined the three-dimensional structure of the protein by X-ray crystallography. In the absence of Ca²âº, substantial parts of the enzyme surrounding the binding sites for the copper ions show structural disorder. Reconstitution of the binuclear CuA site was possible in vitro but required the presence of Ca²âº ions for a stable insertion of the center. In contrast, an excess of Ca²âº prevented copper insertion, and the structural analysis of the Ca²âºapo form revealed that the cation is sufficient to structure the disordered regions of the protein even in the absence of Cu ions, indicating that the geometry of the two noncanonical copper centers is largely predetermined by the protein structure.


Assuntos
Proteínas de Bactérias/química , Cálcio/fisiologia , Oxirredutases/química , Shewanella , Cristalografia por Raios X , Estrutura Secundária de Proteína
16.
J Card Surg ; 30(9): 691-3, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26205095

RESUMO

We report two cases of life-threatening massive hemothorax after titanium plate fixation. We propose a modification of this technique using smaller plates that span the sternal bone but do not encroach upon the cartilage of the ribcage.


Assuntos
Placas Ósseas/efeitos adversos , Hemotórax/etiologia , Hemotórax/prevenção & controle , Procedimentos Ortopédicos/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Esterno/cirurgia , Dispositivos de Fixação Cirúrgica/efeitos adversos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Titânio
17.
J Card Surg ; 29(1): 14-21, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24147730

RESUMO

BACKGROUND: An increasing number of octogenarians are referred for cardiac surgical procedures. In this subset of patients, information on the health-related quality of life (HrQoL) is critical for decision making. However, there is a paucity of prospective data. Thus, we sought to prospectively evaluate the HrQoL in octogenarians undergoing cardiac surgery. METHODS: A prospective HrQoL analysis was performed in 106 elective patients (median age 83.0 ± 2.6 years, range 80-91.8 years, 59.4% male) undergoing cardiac surgery. The standardized SF-36 Health Survey questionnaire was answered preoperatively, and three and 12 months postoperatively. Preoperative data, perioperative outcome, and postoperative morbidity were analyzed. RESULTS: SF-36 scores for physical functioning (44.3 ± 2.3 vs. 52.0 ± 2.7; p < 0.001), role physical (25.2 ± 3.3 vs. 41.5 ± 4.1; p < 0.001), bodily pain (57.8 ± 3.2 vs. 70.7 ± 2.8; p < 0.01), general health (54.9 ± 1.7 vs. 59.6 ± 1.7; p < 0.001), vitality (41.1 ± 2.1 vs. 50.6 ± 2.1; p < 0.001), and mental health (67.5 ± 2.0 vs. 72.4 ± 1.9; p < 0.05) significantly improved from baseline to three months. Social functioning (75.4 ± 2.6 vs. 76.1 ± 2.5; p = 0.79) and role emotional (56.8 ± 4.5 vs. 58.0 ± 4.6; p = 0.29) improved slightly without reaching statistical significance. Correspondingly, at three months, physical component scores increased significantly compared to baseline (34.3 ± 1.0 vs. 39.4 ± 1.0; p < 0.001). SF-36 scores remained stable between three months and one year. No significant change was seen in the mental component score from baseline to three months (48.6 ± 1.2 vs. 49.8 ± 1.1; p = 0.18). CONCLUSIONS: Physical HrQoL is significantly improved in octogenarians three months after cardiac surgery remaining stable at one year postoperatively when compared to baseline.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Qualidade de Vida , Fatores Etários , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/mortalidade , Procedimentos Cirúrgicos Cardíacos/psicologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento
18.
Ann Plast Surg ; 72(2): 155-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23241777

RESUMO

BACKGROUND: Tendon gliding is key to optimal recovery of hand function after complex tendon injuries. Gliding is facilitated by a low-friction gliding surface that is normally provided by the periosteum of the underlying bone. However, significant injuries may damage the periosteum, which must be reconstructed to allow uninterrupted tendon excursion. The absence of the periosteum may compromise a tendon's ability to glide freely, thereby limiting the range of motion. METHODS: Six digits in 4 patients with complex, composite soft tissue defects involving tendon, periosteum, and skin of the hand underwent surgical repair. Each digit had disruption of the bony cortex underlying the tendon injury including periosteal loss. Through an incision on the dorsum of the ipsilateral wrist, an extensor retinaculum graft corresponding to the size of the periosteal defect was harvested. It was then sutured into place over the bare cortex to replace the lost periosteum. RESULTS: All the 6 digits in the 4 patients had complete return to function. Additionally, all patients had near normal strength in the repaired hand along with excellent tendon excursion in both flexion and extension. The average time of follow-up of this series of patients was 1.5 years. CONCLUSIONS: Extensor retinaculum grafting to replace lost periosteum is a technique that is easily used, uses locally available autogenous tissues, and produces excellent tendon function. Additionally, the histologic similarities between extensor retinaculum and periosteum add scientific merit to this novel approach. On the basis of our experience, we recommend the use of extensor retinaculum for periosteal reconstruction to provide an adequate gliding surface for a reconstructed tendon.


Assuntos
Traumatismos dos Dedos/cirurgia , Ligamentos/transplante , Periósteo/lesões , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Traumatismos dos Tendões/cirurgia , Punho , Adulto , Articulações dos Dedos/fisiologia , Articulações dos Dedos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Periósteo/cirurgia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Transplante Autólogo/métodos , Adulto Jovem
19.
Ann Plast Surg ; 73(3): 279-81, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23644443

RESUMO

BACKGROUND: Iatrogenic pneumothorax is a serious intraoperative complication of immediate breast reconstruction with tissue expanders. However, there is paucity of literature regarding incidence or management of intraoperative pneumothorax in the breast reconstruction patient population. METHODS: We performed a retrospective chart review on prospectively collected data from all patients undergoing immediate breast reconstruction with tissue expanders from 1992 to 2012 to determine institutional incidence. We also searched the Nationwide Inpatient Sample database from 1998 to 2008 to determine national incidence. RESULTS: A total of 9653 tissue expanders were placed in 6955 patients at the Memorial Sloan Kettering Cancer Center between 1992 and 2012. There were 3 cases of pneumothorax during immediate breast reconstruction with tissue expanders. The incidence of pneumothorax is 0.03% per expander and 0.04% per patient. From the national database, there were 153 cases of pneumothorax during immediate breast reconstruction with tissue expanders in 27,612 patients. The overall national incidence of pneumothorax is 0.55% per patient. CONCLUSIONS: Our algorithm for management includes a thoracic surgery consultation intraoperatively. A chest tube should be placed at a site distal to the pleurotomy. The site of injury should be repaired primarily or patched as necessary. If the patient remains stable, it is safe to proceed with placement of the tissue expander.


Assuntos
Implantes de Mama/efeitos adversos , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Mamoplastia/efeitos adversos , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Dispositivos para Expansão de Tecidos/efeitos adversos , Algoritmos , Feminino , Humanos , Incidência , Complicações Intraoperatórias/terapia , Mamoplastia/métodos , Pessoa de Meia-Idade , Pneumotórax/terapia , Estudos Retrospectivos
20.
Psychophysiology ; 61(3): e14518, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38200628

RESUMO

Based on the assumption that valence is permanently linked to facial responses, we expected that the corrugator muscle is contracted faster in response to overweight persons than to slim persons, whereas we expected faster contractions of the zygomaticus muscle in response to slim persons rather than to overweight persons. To detect such differences, we conducted experiments with different versions of a facial stimulus-response compatibility task that required participants to respond with the two facial muscles to photos of overweight or slim persons. Contrary to the assumption that valence is permanently linked to facial responses, in Experiments 1 and 2, social categories (overweight vs. slim persons) did not influence the response latencies assessed by electromyography. Whereas in Experiments 1 and 2, neutral labels were used for the muscle responses, in Experiment 3, affective response labels (smile vs. frown) were used. In Experiment 3, faster responses with the corrugator to overweight than to slim persons and with the zygomaticus to slim than to overweight persons were obtained. The influence of task and response label is consistent with the theory of event coding that suggests a more flexible link between valence and action.


Assuntos
Músculos Faciais , Objetivos , Humanos , Músculos Faciais/fisiologia , Sobrepeso , Sorriso , Expressão Facial , Eletromiografia , Emoções/fisiologia
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