Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 193
Filtrar
1.
Gut ; 73(5): 741-750, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38216328

RESUMO

OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. TRIAL REGISTRATION NUMBER: NTR7477.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgia
2.
Neuropsychologia ; 193: 108764, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38141963

RESUMO

Bilinguals possess the ability of expressing themselves in more than one language, and typically do so in contextually rich and dynamic settings. Theories and models have indeed long considered context factors to affect bilingual language production in many ways. However, most experimental studies in this domain have failed to fully incorporate linguistic, social, or physical context aspects, let alone combine them in the same study. Indeed, most experimental psycholinguistic research has taken place in isolated and constrained lab settings with carefully selected words or sentences, rather than under rich and naturalistic conditions. We argue that the most influential experimental paradigms in the psycholinguistic study of bilingual language production fall short of capturing the effects of context on language processing and control presupposed by prominent models. This paper therefore aims to enrich the methodological basis for investigating context aspects in current experimental paradigms and thereby move the field of bilingual language production research forward theoretically. After considering extensions of existing paradigms proposed to address context effects, we present three far-ranging innovative proposals, focusing on virtual reality, dialog situations, and multimodality in the context of bilingual language production.


Assuntos
Multilinguismo , Realidade Virtual , Humanos , Idioma , Linguística , Psicolinguística
3.
Cogn Emot ; 37(5): 997-1005, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37232387

RESUMO

Emotional words have consistently been shown to be processed differently than neutral words. However, few studies have examined individual variability in emotion word processing with longer, ecologically valid stimuli (beyond isolated words, sentences, or paragraphs). In the current study, we re-analysed eye-tracking data collected during story reading to reveal how individual differences in need for affect and narrative absorption impact the speed of emotion word reading. Word emotionality was indexed by affective-aesthetic potentials (AAP) calculated by a sentiment analysis tool. We found that individuals with higher levels of need for affect and narrative absorption read positive words more slowly. On the other hand, these individual differences did not influence the reading time of more negative words, suggesting that high need for affect and narrative absorption are characterised by a positivity bias only. In general, unlike most previous studies using more isolated emotion word stimuli, we observed a quadratic (U-shaped) effect of word emotionality on reading speed, such that both positive and negative words were processed more slowly than neutral words. Taken together, this study emphasises the importance of taking into account individual differences and task context when studying emotion word processing.


Assuntos
Emoções , Individualidade , Humanos , Idioma , Tempo de Reação , Estética
4.
Cortex ; 162: 115-135, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37023479

RESUMO

Mental simulation is an important aspect of narrative reading. In a previous study, we found that gaze durations are differentially impacted by different kinds of mental simulation. Motor simulation, perceptual simulation, and mentalizing as elicited by literary short stories influenced eye movements in distinguishable ways (Mak & Willems, 2019). In the current study, we investigated the existence of a common neural locus for these different kinds of simulation. We additionally investigated whether individual differences during reading, as indexed by the eye movements, are reflected in domain-specific activations in the brain. We found a variety of brain areas activated by simulation-eliciting content, both modality-specific brain areas and a general simulation area. Individual variation in percent signal change in activated areas was related to measures of story appreciation as well as personal characteristics (i.e., transportability, perspective taking). Taken together, these findings suggest that mental simulation is supported by both domain-specific processes grounded in previous experiences, and by the neural mechanisms that underlie higher-order language processing (e.g., situation model building, event indexing, integration).


Assuntos
Tecnologia de Rastreamento Ocular , Leitura , Humanos , Imageamento por Ressonância Magnética/métodos , Idioma , Encéfalo
5.
Res Microbiol ; 174(5): 104049, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36871896

RESUMO

To develop a Bordetella bronchiseptica vaccine with reduced endotoxicity, we previously inactivated lpxL1, the gene encoding the enzyme that incorporates a secondary 2-hydroxy-laurate in lipid A. The mutant showed a myriad of phenotypes. Structural analysis showed the expected loss of the acyl chain but also of glucosamine (GlcN) substituents, which decorate the phosphates in lipid A. To determine which structural change causes the various phenotypes, we inactivated here lgmB, which encodes the GlcN transferase, and lpxL1 in an isogenic background and compared the phenotypes. Like the lpxL1 mutation, the lgmB mutation resulted in reduced potency to activate human TLR4 and to infect macrophages and in increased susceptibility to polymyxin B. These phenotypes are therefore related to the loss of GlcN decorations. The lpxL1 mutation had a stronger effect on hTLR4 activation and additionally resulted in reduced murine TLR4 activation, surface hydrophobicity, and biofilm formation, and in a fortified outer membrane as evidenced by increased resistance to several antimicrobials. These phenotypes, therefore, appear to be related to the loss of the acyl chain. Moreover, we determined the virulence of the mutants in the Galleria mellonella infection model and observed reduced virulence of the lpxL1 mutant but not of the lgmB mutant.


Assuntos
Proteínas de Bactérias , Bordetella bronchiseptica , Lipídeo A , Animais , Humanos , Camundongos , Bordetella bronchiseptica/genética , Lipídeo A/química , Lipídeo A/genética , Macrófagos , Receptor 4 Toll-Like , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
6.
Rev. esp. anestesiol. reanim ; 70(3): 156-159, Mar. 2023. ilus
Artigo em Espanhol | IBECS | ID: ibc-216716

RESUMO

La neumonectomía extrapleural, habitualmente asociada a reconstrucción pericárdica y diafragmática con material protésico, es una de las técnicas quirúrgicas empleadas en el tratamiento del mesotelioma pleural maligno. La herniación de vísceras abdominales hacia el tórax a través del material protésico a nivel diafragmático es una complicación rara, pero potencialmente grave de estos procedimientos, que debe de ser diagnosticada rápidamente para su reparación urgente.Presentamos el caso de un paciente que presentó una herniación gástrica en el postoperatorio precoz de una neumonectomía izquierda por un mesotelioma pleural. Los hallazgos clínicos fueron leves, pero apoyados en las pruebas de imagen, confirmaron la hipótesis diagnóstica y facilitaron la solución del cuadro. Se revisan los posibles factores contribuyentes y se incide en la necesidad de un diagnóstico y tratamiento precoz para evitar la isquemia de las vísceras abdominales herniadas en la cavidad torácica, por el riesgo de necrosis y contaminación por material fecaloideo.(AU)


Extrapleural pneumonectomy, usually associated with pericardial and diaphragmatic reconstruction with prosthetic material, is one of the surgical techniques used in the treatment of malignant pleural mesothelioma. Herniation of the abdominal viscera towards the thorax through the prosthetic material at the diaphragmatic level is a rare but potentially serious complication of these procedures, which must be diagnosed quickly for urgent repair.We present the case of a patient who presented with gastric herniation in the early postoperative period of a left pneumonectomy due to pleural mesothelioma. The clinical findings were mild, but supported by imaging tests, they confirmed the diagnostic hypothesis and facilitated the solution of the condition. Possible contributing factors are reviewed and the need for early diagnosis and treatment is emphasized to avoid ischemia of herniated abdominal viscera in the thoracic cavity, due to the risk of necrosis and contamination by fecaloid material.(AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Mesotelioma , Período Pós-Operatório , Pleuropneumonia , Próteses e Implantes , Complicações Pós-Operatórias , Cirurgia Torácica , Anestesiologia
7.
DNA Repair (Amst) ; 123: 103462, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36738688

RESUMO

Mutation is a phenomenon inescapable for all life-forms, including bacteria. While bacterial mutation rates are generally low due to the operation of error-avoidance systems, sometimes they are elevated by many orders of magnitude. Such a state, known as a hypermutable state, can result from exposure to stress or to harmful environments. Studies of bacterial mutation frequencies and analysis of the precise types of mutations can provide insights into the mechanisms by which mutations occur and the possible involvement of error-avoidance pathways. Several approaches have been used for this, like reporter assays involving non-essential genes or mutation accumulation over multiple generations. However, these approaches give an indirect estimation, and a more direct approach for determining mutations is desirable. With the recent development of a DNA sequencing technique known as Duplex Sequencing, it is possible to detect rare variants in a population at a frequency of 1 in 107 base pairs or less. Here, we have applied Duplex Sequencing to study spontaneous mutations in E. coli. We also investigated the production of replication errors by using a mismatch-repair defective (mutL) strain as well as oxidative-stress associated mutations using a mutT-defective strain. For DNA from a wild-type strain we obtained mutant frequencies in the range of 10-7 to 10-8 depending on the specific base-pair substitution, but we argue that these mutants merely represent a background of the system, rather than mutations that occurred in vivo. In contrast, bona-fide in vivo mutations were identified for DNA from both the mutL and mutT strains, as indicated by specific increases in base substitutions that are fully consistent with their established in vivo roles. Notably, the data reproduce the specific context effects of in vivo mutations as well as the leading vs. lagging strand bias among DNA replication errors.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Mutação , Análise de Sequência de DNA , Replicação do DNA , Reparo do DNA , DNA Bacteriano/genética , Pirofosfatases/genética , Proteínas de Escherichia coli/genética
8.
Front Physiol ; 14: 1111404, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824463

RESUMO

Ammonia accumulation is a major challenge in intensive aquaculture, where fish are fed protein-rich diets in large rations, resulting in increased ammonia production when amino acids are metabolized as energy source. Ammonia is primarily excreted via the gills, which have been found to harbor nitrogen-cycle bacteria that convert ammonia into dinitrogen gas (N2) and therefore present a potential in situ detoxifying mechanism. Here, we determined the impact of feeding strategies (demand-feeding and batch-feeding) with two dietary protein levels on growth, nitrogen excretion, and nitrogen metabolism in common carp (Cyprinus carpio, L.) in a 3-week feeding experiment. Demand-fed fish exhibited significantly higher growth rates, though with lower feed efficiency. When corrected for feed intake, nitrogen excretion was not impacted by feeding strategy or dietary protein, but demand-fed fish had significantly more nitrogen unaccounted for in the nitrogen balance and less retained nitrogen. N2 production of individual fish was measured in all experimental groups, and production rates were in the same order of magnitude as the amount of nitrogen unaccounted for, thus potentially explaining the missing nitrogen in the balance. N2 production by carp was also observed when groups of fish were kept in metabolic chambers. Demand feeding furthermore caused a significant increase in hepatic glutamate dehydrogenase activities, indicating elevated ammonia production. However, branchial ammonia transporter expression levels in these animals were stable or decreased. Together, our results suggest that feeding strategy impacts fish growth and nitrogen metabolism, and that conversion of ammonia to N2 by nitrogen cycle bacteria in the gills may explain the unaccounted nitrogen in the balance.

9.
Rev Esp Anestesiol Reanim (Engl Ed) ; 70(3): 156-159, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36842686

RESUMO

Extrapleural pneumonectomy, usually associated with pericardial and diaphragmatic reconstruction with prosthetic material, is one of the surgical techniques used in the treatment of malignant pleural mesothelioma. Herniation of the abdominal viscera towards the thorax through the prosthetic material at the diaphragmatic level is a rare but potentially serious complication of these procedures, which must be diagnosed quickly for urgent repair. We present the case of a patient who presented with gastric herniation in the early postoperative period of a left pneumonectomy due to pleural mesothelioma. The clinical findings were mild, but supported by imaging tests, they confirmed the diagnostic hypothesis and facilitated the solution of the condition. Possible contributing factors are reviewed and the need for early diagnosis and treatment is emphasized to avoid ischemia of herniated abdominal viscera in the thoracic cavity, due to the risk of necrosis and contamination by fecaloid material.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma Maligno/cirurgia , Pneumonectomia/métodos , Mesotelioma/cirurgia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Neoplasias Pleurais/cirurgia , Próteses e Implantes
10.
Toxins (Basel) ; 15(1)2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36668892

RESUMO

Snake venoms are complex mixtures of toxins that differ on interspecific (between species) and intraspecific (within species) levels. Whether venom variation within a group of closely related species is explained by the presence, absence and/or relative abundances of venom toxins remains largely unknown. Taipans (Oxyuranus spp.) and brown snakes (Pseudonaja spp.) represent medically relevant species of snakes across the Australasian region and provide an excellent model clade for studying interspecific and intraspecific venom variation. Using liquid chromatography with ultraviolet and mass spectrometry detection, we analyzed a total of 31 venoms covering all species of this monophyletic clade, including widespread localities. Our results reveal major interspecific and intraspecific venom variation in Oxyuranus and Pseudonaja species, partially corresponding with their geographical regions and phylogenetic relationships. This extensive venom variability is generated by a combination of the absence/presence and differential abundance of venom toxins. Our study highlights that venom systems can be highly dynamical on the interspecific and intraspecific levels and underscores that the rapid toxin evolvability potentially causes major impacts on neglected tropical snakebites.


Assuntos
Mordeduras de Serpentes , Toxinas Biológicas , Animais , Venenos Elapídicos/genética , Filogenia , Elapidae/genética , Venenos de Serpentes , Serpentes , Antivenenos
11.
Cogn Neurosci ; 14(2): 51-60, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36282102

RESUMO

Understanding emotions and moral intentions of other people is integral to being human. Humanities scholars have long recognized the complex and ambiguous nature of emotions and morality. People are rarely 'just' happy, or sad. Neither are they 'just' good or bad people. Despite this, most knowledge about the psychological and neural basis of emotions and moral understanding comes from experiments investigating unidimensional and non-ambiguous emotions and morality. The goal of this paper is twofold. First I want to point out why mixed and ambiguous emotions and morality are a promising research topic for cognitive neuroscientists. Observing or experiencing mixed or ambiguous emotions and morality tends to have a strong impact on humans. This impact is clearly visible in narratives and fiction, and I will argue that narratives make an excellent stimulus to study the effects of emotional and moral ambiguity. Second, I will sketch a model to help guide research in this promising corner of human cognition.


Assuntos
Emoções , Princípios Morais , Humanos , Cognição
12.
Endosc Int Open ; 10(8): E1127-E1135, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36247075

RESUMO

Background and study aims Endoscopic mucosal resection of large non-pedunculated colorectal polyps is characterized by a high risk of recurrence. Thermal ablation of the mucosal defect margins may reduce recurrence in these lesions, but a systematic overview of the current evidence is lacking. Methods We searched PubMed, Embase and Cochrane until July 2021, for studies on thermal ablation of mucosal defect margins of large non-pedunculated colorectal polyps. Main goal of this meta-analysis was to identify pooled risk difference of recurrence between thermal ablation vs. no adjuvant treatment. Secondary goal was to identify pooled recurrence rate after snare tip soft coagulation (STSC) and argon plasma coagulation (APC). Results Ten studies on thermal ablation of mucosal defect margins were included, with three studies on argon plasma coagulation, six studies on snare tip soft coagulation and one study comparing both treatment modalities, representing a total of 316 APC cases and 1598 STSC cases. Overall pooled risk difference of recurrence was -0.17 (95 % confidence interval [CI] -0.22 to -0.12) as compared to no adjuvant treatment. Pooled risk difference was -0.16 (95 % CI -0.19 to -0.14) for STSC and -0.26 (95 % CI -0.80 to 0.28) for APC. Pooled recurrence rate was 4 % (95 % CI 2 % to 8 %) for STSC and 9 % (95 % CI 4 % to 19 %) for APC. Conclusions Thermal ablation of mucosal defect margins significantly reduces recurrence rate in large non-pedunculated colorectal lesions compared to no adjuvant treatment. While no evidence for superiority exists, STSC may be preferred over APC, because this method is the most evidence-based, and cost-effective modality.

13.
Proc Natl Acad Sci U S A ; 119(37): e2123092119, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36067314

RESUMO

Levels of the cellular dNTPs, the direct precursors for DNA synthesis, are important for DNA replication fidelity, cell cycle control, and resistance against viruses. Escherichia coli encodes a dGTPase (2'-deoxyguanosine-5'-triphosphate [dGTP] triphosphohydrolase [dGTPase]; dgt gene, Dgt) that establishes the normal dGTP level required for accurate DNA replication but also plays a role in protecting E. coli against bacteriophage T7 infection by limiting the dGTP required for viral DNA replication. T7 counteracts Dgt using an inhibitor, the gene 1.2 product (Gp1.2). This interaction is a useful model system for studying the ongoing evolutionary virus/host "arms race." We determined the structure of Gp1.2 by NMR spectroscopy and solved high-resolution cryo-electron microscopy structures of the Dgt-Gp1.2 complex also including either dGTP substrate or GTP coinhibitor bound in the active site. These structures reveal the mechanism by which Gp1.2 inhibits Dgt and indicate that Gp1.2 preferentially binds the GTP-bound form of Dgt. Biochemical assays reveal that the two inhibitors use different modes of inhibition and bind to Dgt in combination to yield enhanced inhibition. We thus propose an in vivo inhibition model wherein the Dgt-Gp1.2 complex equilibrates with GTP to fully inactivate Dgt, limiting dGTP hydrolysis and preserving the dGTP pool for viral DNA replication.


Assuntos
Bacteriófago T7 , Proteínas de Escherichia coli , Escherichia coli , GTP Fosfo-Hidrolases , Guanosina Trifosfato , Proteínas Virais , Bacteriófago T7/fisiologia , Microscopia Crioeletrônica , Replicação do DNA , DNA Viral/metabolismo , Escherichia coli/enzimologia , Escherichia coli/virologia , Proteínas de Escherichia coli/química , GTP Fosfo-Hidrolases/metabolismo , Guanosina Trifosfato/metabolismo , Conformação Proteica , Proteínas Virais/química , Replicação Viral
14.
Ann Med Surg (Lond) ; 80: 104146, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35846862

RESUMO

Introduction: and importance: Upper gastrointestinal (GI) bleeding is common in the clinic. In combination with haemorrhagic shock, morbidity is high. Rapid diagnosis and treatment can save lives. With the introduction of precision imaging several treatment options are feasible. Up-to-date diagnosis and treatment requires expertise from interventional radiology, gastroenterology and surgery to form a dedicated intervention team. This is illustrated by a typical case. Case presentation: We report a 78-year-old otherwise healthy male with a severe diverticulum bleeding. He was initially diagnosed with acute pancreatitis. Approximately 60 minutes after CT scanning, he became haemodynamically instable. He also vomited coffee-like fluid but no clear blood or clots. A repeated CT scan showed active bleeding in the retroperitoneal space highly suspicious for a diverticular bleeding just outside the lumen of the duodenum. An acute multidisciplinary intervention team immediately decided not to perform endoscopy (according to the upper GI bleeding guidelines) but to extend the imaging procedure with digital subtraction angiography (DSA). By this time, active bleeding from a side branch of the gastroduodenal artery was noted and successfully coiled. Clinical discussion: Guidelines determine day-to-day management in clinical medicine. Still, there is an exception to every rule. The case presented here was typical of upper GI bleeding with haemodynamic instability and signs of shock, but without haematemesis. This combination indicated a bleeding from somewhere outside the lumen of the GI tract. Instead of endoscopy, the acute intervention team decided to perform CT angiography (CTa) with subsequent DSA. On imaging, the bleeding focus was immediately identified and treated by coiling. Conclusion: Performance of CTa immediately followed by DSA and no endoscopy was decided by an acute intervention team in a patient with upper GI bleeding and haemorrhagic shock. Swift coiling of the bleeding artery outside the GI tract lumen was successful. The team in charge relied on a hybrid multifunctional unit fully equipped to perform interventional radiologic as well as GI procedures.

15.
Cogn Res Princ Implic ; 7(1): 72, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35907147

RESUMO

When two people read the same story, they might both end up liking it very much. However, this does not necessarily mean that their reasons for liking it were identical. We therefore ask what factors contribute to "liking" a story, and-most importantly-how people vary in this respect. We found that readers like stories because they find them interesting, amusing, suspenseful and/or beautiful. However, the degree to which these components of appreciation were related to how much readers liked stories differed between individuals. Interestingly, the individual slopes of the relationships between many of the components and liking were (positively or negatively) correlated. This indicated, for instance, that individuals displaying a relatively strong relationship between interest and liking, generally display a relatively weak relationship between sadness and liking. The individual differences in the strengths of the relationships between the components and liking were not related to individual differences in expertize, a characteristic strongly associated with aesthetic appreciation of visual art. Our work illustrates that it is important to take into consideration the fact that individuals differ in how they arrive at their evaluation of literary stories, and that it is possible to quantify these differences in empirical experiments. Our work suggests that future research should be careful about "overfitting" theories of aesthetic appreciation to an "idealized reader," but rather take into consideration variations across individuals in the reason for liking a particular story.


Assuntos
Emoções , Leitura , Estética , Humanos , Individualidade , Narração
16.
J Biol Chem ; 298(7): 102073, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35643313

RESUMO

Deoxynucleoside triphosphate (dNTP) triphosphohydrolases (dNTPases) are important enzymes that may perform multiple functions in the cell, including regulating the dNTP pools and contributing to innate immunity against viruses. Among the homologs that are best studied are human sterile alpha motif and HD domain-containing protein 1 (SAMHD1), a tetrameric dNTPase, and the hexameric Escherichia coli dGTPase; however, it is unclear whether these are representative of all dNTPases given their wide distribution throughout life. Here, we investigated a hexameric homolog from the marine bacterium Leeuwenhoekiella blandensis, revealing that it is a dGTPase that is subject to allosteric activation by dATP, specifically. Allosteric regulation mediated solely by dATP represents a novel regulatory feature among dNTPases that may facilitate maintenance of cellular dNTP pools in L. blandensis. We present high-resolution X-ray crystallographic structures (1.80-2.26 Å) in catalytically important conformations as well as cryo-EM structures (2.1-2.7 Å) of the enzyme bound to dGTP and dATP ligands. The structures, the highest resolution cryo-EM structures of any SAMHD1-like dNTPase to date, reveal an intact metal-binding site with the dGTP substrate coordinated to three metal ions. These structural and biochemical data yield insights into the catalytic mechanism and support a conserved catalytic mechanism for the tetrameric and hexameric dNTPase homologs. We conclude that the allosteric activation by dATP appears to rely on structural connectivity between the allosteric and active sites, as opposed to the changes in oligomeric state upon ligand binding used by SAMHD1.


Assuntos
Proteínas Monoméricas de Ligação ao GTP , Regulação Alostérica/fisiologia , Escherichia coli/metabolismo , Flavobacteriaceae , Humanos , Modelos Moleculares , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteína 1 com Domínio SAM e Domínio HD/metabolismo
17.
Inflamm Bowel Dis ; 28(9): 1309-1320, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35554535

RESUMO

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal cancer (CRC) compared to patients with IBD only. The aim of this study was to perform an extensive screen of known carcinogenic genomic alterations in patients with PSC-IBD, and to investigate whether such changes occur already in nondysplastic mucosa. METHODS: Archival cancer tissue and nondysplastic mucosa from resection specimens of 19 patients with PSC-IBD-CRC were characterized, determining DNA copy-number variations, microsatellite instability (MSI), mutations on 48 cancer genes, and CpG island methylator phenotype (CIMP). Genetic profiles were compared with 2 published cohorts of IBD-associated CRC (IBD-CRC; n = 11) and sporadic CRC (s-CRC; n = 100). RESULTS: Patterns of chromosomal aberrations in PSC-IBD-CRC were similar to those observed in IBD-CRC and s-CRC, MSI occurred only once. Mutation frequencies were comparable between the groups, except for mutations in KRAS, which were less frequent in PSC-IBD-CRC (5%) versus IBD-CRC (38%) and s-CRC (31%; P = .034), and in APC, which were less frequent in PSC-IBD-CRC (5%) and IBD-CRC (0%) versus s-CRC (50%; P < .001). Cases of PSC-IBD-CRC were frequently CIMP positive (44%), at similar levels to cases of s-CRC (34%; P = .574) but less frequent than in cases with IBD-CRC (90%; P = .037). Similar copy number aberrations and mutations were present in matched cancers and adjacent mucosa in 5/15 and 7/11 patients, respectively. CONCLUSIONS: The excess risk of CRC in patients with PSC-IBD was not explained by copy number aberrations, mutations, MSI, nor CIMP status, in cancer tissue, nor in adjacent mucosa. These findings set the stage for further exome-wide and epigenetic studies.


The excessive risk of colorectal carcinoma (CRC) in patients with both primary sclerosing cholangitis and inflammatory bowel disease (IBD) was not explained by an extensive screen of copy number aberrations, mutations, microsatellite instability, and CpG island methylator phenotype status when compared with patients with IBD-CRC and sporadic CRC.


Assuntos
Colangite Esclerosante , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Colangite Esclerosante/complicações , Colangite Esclerosante/genética , Colangite Esclerosante/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/genética , Perfil Genético , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Instabilidade de Microssatélites
18.
Rev Esp Anestesiol Reanim (Engl Ed) ; 69(5): 266-301, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35610172

RESUMO

The introduction of video-assisted thoracoscopic (VATS) techniques has led to a new approach in thoracic surgery. VATS is performed by inserting a thoracoscope through a small incisions in the chest wall, thus maximizing the preservation of muscle and tissue. Because of its low rate of morbidity and mortality, VATS is currently the technique of choice in most thoracic procedures. Lung resection by VATS reduces prolonged air leaks, arrhythmia, pneumonia, postoperative pain and inflammatory markers. This reduction in postoperative complications shortens hospital length of stay, and is particularly beneficial in high-risk patients with low tolerance to thoracotomy. Compared with conventional thoracotomy, the oncological results of VATS surgery are similar or even superior to those of open surgery. This aim of this multidisciplinary position statement produced by the thoracic surgery working group of the Spanish Society of Anesthesiology and Reanimation (SEDAR), the Spanish Society of Thoracic Surgery (SECT), and the Spanish Association of Physiotherapy (AEF) is to standardize and disseminate a series of perioperative anaesthesia management guidelines for patients undergoing VATS lung resection surgery. Each recommendation is based on an in-depth review of the available literature by the authors. In this document, the care of patients undergoing VATS surgery is organized in sections, starting with the surgical approach, and followed by the three pillars of anaesthesia management: preoperative, intraoperative, and postoperative anaesthesia.


Assuntos
Anestesia , Anestesiologia , Cirurgia Torácica , Humanos , Pulmão , Modalidades de Fisioterapia , Pneumonectomia/efeitos adversos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos
19.
Biol Rev Camb Philos Soc ; 97(5): 1823-1843, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35580905

RESUMO

Convergence is the phenomenon whereby similar phenotypes evolve independently in different lineages. One example is resistance to toxins in animals. Toxins have evolved many times throughout the tree of life. They disrupt molecular and physiological pathways in target species, thereby incapacitating prey or deterring a predator. In response, molecular resistance has evolved in many species exposed to toxins to counteract their harmful effects. Here, we review current knowledge on the convergence of toxin resistance using examples from a wide range of toxin families. We explore the evolutionary processes and molecular adaptations driving toxin resistance. However, resistance adaptations may carry a fitness cost if they disrupt the normal physiology of the resistant animal. Therefore, there is a trade-off between maintaining a functional molecular target and reducing toxin susceptibility. There are relatively few solutions that satisfy this trade-off. As a result, we see a small set of molecular adaptations appearing repeatedly in diverse animal lineages, a phenomenon that is consistent with models of deterministic evolution. Convergence may also explain what has been called 'autoresistance'. This is often thought to have evolved for self-protection, but we argue instead that it may be a consequence of poisonous animals feeding on toxic prey. Toxin resistance provides a unique and compelling model system for studying the interplay between trophic interactions, selection pressures and the molecular mechanisms underlying evolutionary novelties.


Assuntos
Adaptação Fisiológica , Evolução Biológica , Adaptação Fisiológica/genética , Animais , Fenótipo
20.
Psychon Bull Rev ; 29(5): 1703-1718, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35318585

RESUMO

It is often argued that narratives improve social cognition, either by appealing to social-cognitive abilities as we engage with the story world and its characters, or by conveying social knowledge. Empirical studies have found support for both a correlational and a causal link between exposure to (literary, fictional) narratives and social cognition. However, a series of failed replications has cast doubt on the robustness of these claims. Here, we review the existing empirical literature and identify open questions and challenges. An important conclusion of the review is that previous research has given too little consideration to the diversity of narratives, readers, and social-cognitive processes involved in the social-cognitive potential of narratives. We therefore establish a research agenda, proposing that future research should focus on (1) the specific text characteristics that drive the social-cognitive potential of narratives, (2) the individual differences between readers with respect to their sensitivity to this potential, and (3) the various aspects of social cognition that are potentially affected by reading narratives. Our recommendations can guide the design of future studies that will help us understand how, for whom, and in what respect exposure to narratives can advantage social cognition.


Assuntos
Leitura , Cognição Social , Cognição , Emoções , Humanos , Narração
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...