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BACKGROUND: Current treatment modalities for spontaneous esophageal perforation remain controversial because of their rarity. OBJECTIVE: To describe our institution's experience in managing patients with spontaneous esophageal rupture and conduct a meta-analysis of existing studies to determine the best evidence-based treatment options. METHODS: We enrolled patients with spontaneous esophageal rupture who underwent their first treatment at our institution. We also identified studies through a systematic search of the MEDLINE, EMBASE, and Cochrane Library databases before April 1, 2024, for inclusion in the meta-analysis. RESULTS: This case series included data from 17 patients with delayed diagnosis who were treated with esophageal stents, with an immediate mortality rate of 5.9%. In addition to the cases from our institution, we obtained 944 patients from 46 studies in the final analysis. The combined immediate mortality rate was 11% (95% confidence interval [CI]: 0.08-0.15). The combined re-intervention rate was 11% (95% CI: 0.05-0.19). The combined immediate mortality was 6% (95% CI: 0.04-0.09) after primary closure, 14% (95% CI: 0.02-0.32) after T-tube drain repair, 2% (95% CI: 0.00-0.15) after esophagectomy, 8% (95% CI: 0.03-0.15) after stent placement, and 22% (95% CI: 0.03-0.47) after conservative treatment. The subgroup analysis based on the timing of the intervention showed that the immediate mortality rate in patients initiating treatment within 24 h of rupture was 3% (95% CI: 0.01-0.08), whereas that in patients initiating treatment > 24 h later was 12% (95% CI: 0.08-0.18). CONCLUSION: Outcomes are best after esophagectomy, and primary closure or esophageal stenting is a good option compared with other treatment modalities. Prognosis is related to the timing of intervention, and accurate diagnosis and treatment within 24 h significantly reduces the risk of death in patients. Patients with delayed diagnosis may have a better prognosis with stent placement.
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Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals' movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.
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The ubiquitin-proteasome system (UPS) is a basic regulatory mechanism in cells that is essential for maintaining cell homeostasis, stimulating signal transduction, and determining cell fate. These biological processes require coordinated signaling cascades across members of the UPS to achieve substrate ubiquitination and deubiquitination. The role of the UPS in fibrotic diseases has attracted widespread attention, and the aberrant expression of UPS members affects the fibrosis process. In this review, we provide an overview of the UPS and its relevance for fibrotic diseases. Moreover, for the first time, we explore in detail how the UPS promotes or inhibits renal fibrosis by regulating biological processes such as signaling pathways, inflammation, oxidative stress, and the cell cycle, emphasizing the status and role of the UPS in renal fibrosis. Further research on this system may reveal new strategies for preventing renal fibrosis.
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Emerging evidence has linked the dysregulation of N6-methyladenosine (m6A) modification to inflammation and inflammatory diseases, but the underlying mechanism still needs investigation. Here, we found that high levels of m6A modification in a variety of hyperinflammatory states are p65-dependent because Wilms tumor 1-associated protein (WTAP), a key component of the "writer" complex, is transcriptionally regulated by p65, and its overexpression can lead to increased levels of m6A modification. Mechanistically, upregulated WTAP is more prone to phase separation to facilitate the aggregation of the writer complex to nuclear speckles and the deposition of m6A marks on transcriptionally active inflammatory transcripts, thereby accelerating the proinflammatory response. Further, a myeloid deficiency in WTAP attenuates the severity of LPS-induced sepsis and DSS-induced IBD. Thus, the proinflammatory effect of WTAP is a general risk-increasing mechanism, and interrupting the assembly of the m6A writer complex to reduce the global m6A levels by targeting the phase separation of WTAP may be a potential and promising therapeutic strategy for alleviating hyperinflammation.
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Adenosina , Proteínas de Ciclo Celular , Inflamação , Fatores de Processamento de RNA , Animais , Humanos , Camundongos , Adenosina/metabolismo , Adenosina/análogos & derivados , Modelos Animais de Doenças , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos , Camundongos Knockout , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Sepse/metabolismo , Sepse/genética , Sepse/patologia , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genéticaRESUMO
Metasurface holograms represent a common category of metasurface devices that utilize in-plane phase gradients to shape wavefronts, forming holographic images through the application of the generalized Snell's law (GSL). While conventional metasurfaces focus solely on phase gradients, metagratings, which incorporate higher-order wave diffraction, further expand the GSL's generality. Recent advances in certain acoustic metagratings demonstrate an updated GSL extension capable of reversing anomalous transmission and reflection, whose reversal is characterized by the parity of the number of wave propagation trips through the metagrating. However, the current extension of GSL remains limited to 1D metagratings, unable to access 2D holographic images in 3D spaces. Here, the GSL extension to 2D metagratings for manipulating waves within 3D spaces is investigated. Through this analysis, a series of acoustic metagrating holograms is experimentally demonstrated. These holographic images exhibit the unique ability to switch between transmission and reflection types independently. This study introduces an additional dimension to modern holography design and metasurface wavefront manipulation.
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Ischemic stroke is the second leading cause of death and disability worldwide, and efforts to prevent stroke, mitigate secondary neurological damage, and promote neurological recovery remain paramount. Recent findings highlight the critical importance of microbiome-related metabolites, including vitamin B12 (VB12), in alleviating toxic stroke-associated neuroinflammation. Here, we showed that VB12 tonically programmed genes supporting microglial cell division and activation and critically controlled cellular fatty acid metabolism in homeostasis. Intriguingly, VB12 promoted mitochondrial transcriptional and metabolic activities and significantly restricted stroke-associated gene alterations in microglia. Furthermore, VB12 differentially altered the functions of microglial subsets during the acute phase of ischemic stroke, resulting in reduced brain damage and improved neurological function. Pharmacological depletion of microglia before ischemic stroke abolished VB12-mediated neurological improvement. Thus, our preclinical studies highlight the relevance of VB12 in the functional programming of microglia to alleviate neuroinflammation, minimize ischemic injury, and improve host neurological recovery after ischemic stroke.
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Objectives were to assess differences in uterine microbiome associated with clinical cure and pregnancy outcomes in dairy cows treated for metritis. Cows with metritis (reddish-brownish, watery, and fetid vaginal discharge) were paired with cows without metritis based on parity and days postpartum. Uterine contents were collected through transcervical lavage at diagnosis, five days later following antimicrobial therapy (day 5), and at 40 days postpartum. Uterine microbiome was assessed by sequencing the V4 hypervariable region of the 16S rRNA gene. Although alpha-diversity based on Chao1, Shannon, and inverse Simpson indexes at diagnosis did not differ between cows with and without metritis, disease was associated with differences in beta-diversity. Prevalence of Porphyromonas, Bacteroides, and Veillonella was greater in cows with metritis. Streptococcus, Sphingomonas, and Ureaplasma were more prevalent in cows without metritis. Differences in beta-diversity between cows with and without metritis persisted on day 5. Uterine microbiome was not associated with clinical cure. Richness and alpha-diversity, but not beta-diversity, of uterine microbiome 40 days postpartum were associated with metritis and pregnancy. No relationship between uterine microbiome and pregnancy outcomes was observed. Results indicate that factors other than changes in intrauterine bacterial community underlie fertility loss and clinical cure in cows with metritis.
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Doenças dos Bovinos , Endometrite , Microbiota , Resultado da Gravidez , RNA Ribossômico 16S , Útero , Feminino , Animais , Bovinos , Gravidez , Útero/microbiologia , Endometrite/microbiologia , Endometrite/veterinária , Endometrite/tratamento farmacológico , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/terapia , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificaçãoRESUMO
BACKGROUND & AIMS: Putative anion transporter-1 (PAT1, SLC26A6) plays a key role in intestinal oxalate and bicarbonate secretion. PAT1 knockout (PKO) mice exhibit hyperoxaluria and nephrolithiasis. Notably, diseases such as inflammatory bowel disease are also associated with higher risk of hyperoxaluria and nephrolithiasis. However, the potential role of PAT1 deficiency in gut-barrier integrity and susceptibility to colitis is currently elusive. METHODS: Age-matched PKO and wild-type littermates were administered 3.5% dextran sulfate sodium in drinking water for 6 days. Ileum and colon of control and treated mice were harvested. Messenger RNA and protein expression of tight junction proteins were determined by reverse transcription polymerase chain reaction and western blotting. Severity of inflammation was assessed by measuring diarrheal phenotype, cytokine expression, and hematoxylin and eosin staining. Gut microbiome and associated metabolome were analyzed by 16S ribosomal RNA sequencing and mass spectrometry, respectively. RESULTS: PKO mice exhibited significantly higher loss of body weight, gut permeability, colonic inflammation, and diarrhea in response to dextran sulfate sodium treatment. In addition, PKO mice showed microbial dysbiosis and significantly reduced levels of butyrate and butyrate-producing microbes compared with controls. Co-housing wild-type and PKO mice for 4 weeks resulted in PKO-like signatures on the expression of tight junction proteins in the colons of wild-type mice. CONCLUSIONS: Our data demonstrate that loss of PAT1 disrupts gut microbiome and related metabolites, decreases gut-barrier integrity, and increases host susceptibility to intestinal inflammation. These findings, thus, highlight a novel role of the oxalate transporter PAT1 in promoting gut-barrier integrity, and its deficiency appears to contribute to the pathogenesis of inflammatory bowel diseases.
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Colite , Colo , Sulfato de Dextrana , Disbiose , Microbioma Gastrointestinal , Camundongos Knockout , Permeabilidade , Transportadores de Sulfato , Animais , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo , Sulfato de Dextrana/toxicidade , Colite/microbiologia , Colite/metabolismo , Colite/induzido quimicamente , Colite/patologia , Colite/genética , Camundongos , Colo/microbiologia , Colo/patologia , Colo/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Modelos Animais de Doenças , Íleo/patologia , Íleo/microbiologia , Íleo/metabolismo , Diarreia/microbiologia , Diarreia/metabolismo , Proteínas de Junções Íntimas/metabolismo , Proteínas de Junções Íntimas/genética , Camundongos Endogâmicos C57BL , Masculino , Antiporters/genética , Antiporters/metabolismo , Antiporters/deficiênciaRESUMO
The impact protection applications of polycarbonate (PC) products are gradually increasing. Due to the high sensitivity of PC to notches, research on notch impacts has become very important. In this paper, the impact performance of PC with two different molecular weights under different notch states was investigated. Three notch size factors, namely notch tip radius, notch angle, and notch center depth, were selected to design orthogonal experiments and research impact toughness. Subsequently, a single-factor study was conducted on the impact radius at the tip of the notch, which was the most important factor affecting the impact performance. Research shows that the brittle-ductile-transition tip radius of high-molecular-weight PC is 0.15 mm, and it has a higher impact toughness than low-molecular-weight PC during the brittle fracture process. The brittle-ductile-transition tip radius of lower molecular weight is 0.25 mm, while low-molecular-weight PC has a higher impact toughness during the ductile fracture process. The brittle and ductile fracture mechanisms of PC with different molecular weights were analyzed by observing the stress changes and cross-sectional morphology.
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Background: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism. Methods: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient). Results: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1ß,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine). Conclusion: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.
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The maintenance of regulatory T (Treg) cells critically prevents autoimmunity. Pre-B cell leukemia transcription factor 1 (Pbx1) variants are associated with lupus susceptibility, particularly through the expression of a dominant negative isoform Pbx1-d in CD4+ T cells. Pbx1-d overexpression impaired Treg cell homeostasis and promoted inflammatory CD4+ T cells. Here, we showed a high expression of Pbx1 in human and murine Treg cells, which is decreased in lupus patients and mice. Pbx1 deficiency or Pbx1-d overexpression reduced the number, stability, and suppressive activity of Treg cells, which increased murine responses to immunization and autoimmune induction. Mechanistically, Pbx1 deficiency altered the expression of genes implicated in cell cycle and apoptosis in Treg cells. Intriguingly, Rtkn2, a Rho-GTPase previously associated with Treg homeostasis, was directly transactivated by Pbx1. Our results suggest that the maintenance of Treg cell homeostasis and stability by Pbx1 through cell cycle progression prevent the expansion of inflammatory T cells that otherwise exacerbates lupus progression in the hosts.
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Lúpus Eritematoso Sistêmico , Linfócitos T Reguladores , Animais , Humanos , Camundongos , Divisão Celular , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B/metabolismo , Isoformas de Proteínas/genética , Lúpus Eritematoso Sistêmico/genéticaRESUMO
As hypothetical topological defects in the geometry of spacetime, vortex strings could have played many roles in cosmology, and their distinct features can provide observable clues about the early universe's evolution. A key feature of vortex strings is that they can interact with Weyl fermionic modes and support massless chiral-anomaly states along strings. To date, despite many attempts to detect vortex strings in astrophysics or to emulate them in artificially created systems, observation of these vortex-string chiral modes remains experimentally elusive. Here we report experimental observations of vortex-string chiral modes using a metamaterial system. This is implemented by inhomogeneous perturbation of Yang-monopole phononic metamaterials. The measured linear dispersion and modal profiles confirm the existence of topological modes bound to and propagating along the string with the chiral anomaly. Our work provides a platform for studying diverse cosmic topological defects in astrophysics and offers applications as topological fibres in communication techniques.
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When electrons moving in two dimensions (2D) are subjected to a strong uniform magnetic field, they form flat bands called Landau levels (LLs). LLs can also arise from pseudomagnetic fields (PMFs) induced by lattice distortions. In three-dimensional (3D) systems, there has been no experimental demonstration of LLs as a type of flat band thus far. Here, we report the experimental realization of a flat 3D LL in an acoustic crystal. Starting from a lattice whose bandstructure exhibits a nodal ring, we design an inhomogeneous distortion corresponding to a specific pseudomagnetic vector potential (PVP). This distortion causes the nodal ring states to break up into LLs, including a zeroth LL that is flat along all three directions. These findings suggest the possibility of using nodal ring materials to generate 3D flat bands, allowing access to strong interactions and other attractive physical regimes in 3D.
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Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3' untranslated regions (3' UTRs). Our previous study has revealed the global 3' UTR shortening of host mRNAs through APA upon viral infection. However, how the dynamic changes in the APA landscape occur upon viral infection remains largely unknown. Here we further found that, the reduced protein abundance of CPSF6, one of the core 3' processing factors, promotes the usage of proximal poly(A) sites (pPASs) of many immune related genes in macrophages and fibroblasts upon viral infection. Shortening of the 3' UTR of these transcripts may improve their mRNA stability and translation efficiency, leading to the promotion of type I IFN (IFN-I) signalling-based antiviral immune responses. In addition, dysregulated expression of CPSF6 is also observed in many immune related physiological and pathological conditions, especially in various infections and cancers. Thus, the global APA dynamics of immune genes regulated by CPSF6, can fine-tune the antiviral response as well as the responses to other cellular stresses to maintain the tissue homeostasis, which may represent a novel regulatory mechanism for antiviral immunity.
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Poliadenilação , Viroses , Fatores de Poliadenilação e Clivagem de mRNA , Humanos , Regiões 3' não Traduzidas/genética , Regulação para Baixo , Imunidade/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Fatores de Poliadenilação e Clivagem de mRNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Viroses/genética , Camundongos , AnimaisRESUMO
To compare the learning curve of mediastinal mass resection between robot-assisted surgery and thoracoscopic surgery. Retrospective perioperative data were collected from 160 mediastinal mass resection cases. Data included 80 initial consecutive video-assisted thoracoscopic surgery (VATS) resection cases performed from February 2018 to February 2020 and 80 initial consecutive robotic-assisted thoracic surgery (RATS) resection cases performed from March 2020 to March 2023. All cases were operated on by a thoracic surgeon. The clinical characteristics and perioperative outcomes of the two groups were compared. The operation time in both the RATS group and VATS group was analyzed using the cumulative sum (CUSUM) method. Based on this method, the learning curves of both groups were divided into a learning period and mastery period. The VATS group and the RATS group crossed the inflection point in the 27th and 21st case, respectively. Subsequently, we found that the learning period was longer than the mastery period with statistically significant differences in terms of the operating time, and postoperative hospital stay in the VATS group and the RATS group. A certain amount of VATS experience can shorten the learning curve for RATS.
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Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Estudos Retrospectivos , Curva de Aprendizado , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Torácica Vídeoassistida/métodosRESUMO
Factorization machines (FMs) are widely used in recommender systems due to their adaptability and ability to learn from sparse data. However, for the ubiquitous non-interactive features in sparse data, existing FMs can only estimate the parameters corresponding to these features via the inner product of their embeddings. Undeniably, they cannot learn the direct interactions of these features, which limits the model's expressive power. To this end, we first present MixFM, inspired by Mixup, to generate auxiliary training data to boost FMs. Unlike existing augmentation strategies that require labor costs and expertise to collect additional information such as position and fields, these augmented data are only by the convex combination of the raw ones without any professional knowledge support. More importantly, if non-interactive features exist in parent samples to be mixed respectively, MixFM will establish their direct interactions. Second, considering that MixFM may generate redundant or even detrimental instances, we further put forward a novel Factorization Machine powered by Saliency-guided Mixup (denoted as SMFM). Guided by the customized saliency, SMFM can generate more informative neighbor data. Through theoretical analysis, we prove that the proposed methods minimize the upper bound of the generalization error, which positively enhances FMs. Finally, extensive experiments on seven datasets confirm that our approaches are superior to baselines. Notably, the results also show that "poisoning" mixed data benefits the FM variants.
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BACKGROUND: In various surgical specialties, preoperative surgical warm-up has been demonstrated to affect a surgeon's performance and the perioperative outcomes for patients. However, the influence of warm-up activities on video-assisted thoracoscopic surgery lobectomy (VATSL) remains largely unexplored. This study aims to investigate the potential effects of preoperative surgical warm-up on VATSL. METHODS: A cohort of 364 patients diagnosed with lung cancer through pathology and undergoing VATSL at the Thoracic Surgery Department of Xuzhou Medical University from January 2018 to September 2022 were included. Patients were categorized into two groups: the warm-up group, comprising 172 patients undergoing their first VATSL of the day, and the warm-up effect group, consisting of 192 patients undergoing their second VATSL on the same day. Propensity score matching was employed to compare operation times and postoperative complications between the two groups, resulting in 159 matched cases in each group. RESULTS: There were no statistically significant differences in operation time (154.5 ± 54.9 vs. 147.2 ± 54.4 min, p = 0.239) and postoperative complications (including pulmonary infection, atelectasis, long-term pulmonary air leakage requiring incision suture in the operating room, and postoperative pleural effusion) (14:22 cases, p = 0.157) between the warm-up and warm-up effect groups. CONCLUSION: The findings suggest that preoperative surgical warm-up does not significantly affect the perioperative outcomes of VATSL.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Cirurgiões , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Pneumonectomia/métodos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
Tryptophan modulates disease activity and the composition of microbiota in the B6.Sle1.Sle2.Sle3 (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of Ruminococcus gnavus (Rg), a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. Rg depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with Rg showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.
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AIM: To evaluate the effect of different oral irrigators on the sub-gingival microbiome composition in patients with naturally occurring plaque-induced gingivitis. MATERIALS AND METHODS: Sub-gingival plaque was collected from adults participating in a clinical trial assessing the efficacy of oral hygiene with two different oral irrigators (Waterpik Water Flosser [Group 1] and Oral-B Water Flosser [Group 2]) versus dental flossing (Group 3) for microbiome analysis. Plaque samples were reflective of naturally occurring plaque-induced gingivitis at baseline and of gingival health at the endpoint (4 weeks). Clinical measures of gingival inflammation were collected, and the sub-gingival microbiome was analysed by 16S rRNA sequencing to identify amplicon sequence variants. RESULTS: Oral hygiene instruction with self-performed manual toothbrushing and water-jet irrigation led to significant reductions in inflammation for all groups; both oral irrigators outperformed flossing in bleeding-on-probing reduction (p < .001). Microbiome diversity of sub-gingival plaque remained relatively stable over time, but significant changes were noted in certain taxa, consistent with increases in the relative abundance of commensals and reductions in late colonizers and periodontal pathogens in the water-jet groups. CONCLUSIONS: Reduction in gingival inflammation at 4 weeks within the water-jet groups is accompanied by slight but critical changes in microbiome composition. Although biodiversity does not substantially change within 4 weeks during the resolution of naturally induced gingivitis, significant relative increases in commensal early colonizers such as Streptococcus, Veillonella and Fusobacterium were accompanied by a shift towards a less anaerobic microbiota associated with return to health. These changes were contingent upon the type of interdental hygiene, with Group 1 exhibiting more significant alterations in microbiome composition towards a periodontal-health-compatible community.
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Placa Dentária , Gengivite , Adulto , Humanos , Higiene Bucal , Dispositivos para o Cuidado Bucal Domiciliar , Análise de Dados Secundários , RNA Ribossômico 16S , Índice de Placa Dentária , Escovação Dentária , Gengivite/prevenção & controle , Placa Dentária/prevenção & controle , Inflamação , Água , Método Simples-CegoRESUMO
BACKGROUND: Chronic cough is common after lobectomy. Vagus nerves are part of the cough reflex. Accordingly, transection of the pulmonary branches of vagus nerve may prevent chronic cough. And there are no clear recommendations on the management of the pulmonary branches of vagus in any thoracic surgery guidelines. METHODS: This is a single-center, randomized controlled trial. Adult patients undergoing elective video-assisted thoracoscopic lobectomy and lymphadenectomy were randomized at a 1:1 ratio to undergo a sham procedure (control group) or transection of the pulmonary branches of the vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch of the vagus nerve. The primary outcome was the rate of chronic cough, as assessed at 3 months after surgery in the intent-to-treat population. RESULTS: Between 1 February 2020 and 1 August 2020, 116 patients (59.6±10.1 years of age; 45 men) were randomized (58 in each group). All patients received designated intervention. The rate of chronic cough at 3 months was 19.0% (11/58) in the vagotomy group versus 41.4% (24/58) in the control group (OR=0.332, 95% CI: 0.143-0.767; P =0.009). In the 108 patients with 2-year assessment, the rate of persistent cough was 12.7% (7/55) in the control and 1.9% (1/53) in the vagotomy group ( P =0.032). The two groups did not differ in postoperative complications and key measures of pulmonary function, for example, maximal voluntary ventilation, diffusing capacity of the lungs for carbon monoxide, and forced expiratory volume. CONCLUSION: Transecting the pulmonary branches of vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch decreased the rate of chronic cough without affecting pulmonary function in patients undergoing video-assisted lobectomy and lymphadenectomy.