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1.
Funct Integr Genomics ; 24(4): 120, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38960936

RESUMO

The Drosophila egg chamber (EC) starts as a spherical tissue at the beginning. With maturation, the outer follicle cells of EC collectively migrate in a direction perpendicular to the anterior-posterior axis, to shape EC from spherical to ellipsoidal. Filamentous actin (F-actin) plays a significant role in shaping individual migratory cells to the overall EC shape, like in every cell migration. The primary focus of this article is to unveil the function of different Actin Binding Proteins (ABPs) in regulating mature Drosophila egg shape. We have screened 66 ABPs, and the genetic screening data revealed that individual knockdown of Arp2/3 complex genes and the "capping protein ß" (cpb) gene have severely altered the egg phenotype. Arpc1 and cpb RNAi mediated knockdown resulted in the formation of spherical eggs which are devoid of dorsal appendages. Studies also showed the role of Arpc1 and cpb on the number of laid eggs and follicle cell morphology. Furthermore, the depletion of Arpc1 and cpb resulted in a change in F-actin quantity. Together, the data indicate that Arpc1 and cpb regulate Drosophila egg shape, F-actin management, egg-laying characteristics and dorsal appendages formation.


Assuntos
Actinas , Proteínas de Drosophila , Morfogênese , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Actinas/metabolismo , Actinas/genética , Feminino , Morfogênese/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/genética , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Proteínas de Capeamento de Actina/metabolismo , Proteínas de Capeamento de Actina/genética , Óvulo/metabolismo , Óvulo/crescimento & desenvolvimento
2.
Biochem J ; 480(5): 297-306, 2023 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-36825663

RESUMO

The nine-amino-acid transactivation domains (9aaTAD) was identified in numerous transcription factors including Gal4, p53, E2A, MLL, c-Myc, N-Myc, and also in SP, KLF, and SOX families. Most of the 9aaTAD domains interact with the KIX domain of transcription mediators MED15 and CBP to activate transcription. The NFkB activation domain occupied the same position on the KIX domain as the 9aaTADs of MLL, E2A, and p53. Binding of the KIX domain is established by the two-point interaction involving 9aaTAD positions p3-4 and p6-7. The NFkB primary binding region (positions p3-4) is almost identical with MLL and E2A, but secondary NFkB binding region differs by the position and engages the distal NFkB region p10-11. Thus, the NFkB activation domain is five amino acids longer than the other 9aaTADs. The NFkB activation domain includes an additional region, which we called the Omichinski Insert extending activation domain length to 14 amino acids. By deletion, we demonstrated that Omichinski Insert is an entirely non-essential part of NFkB activation domain. In summary, we recognized the NFkB activation domain as prolonged 9aaTAD conserved in evolution from humans to amphibians.


Assuntos
Aminoácidos , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Aminoácidos/metabolismo , Sequência de Aminoácidos , Ativação Transcricional , Fatores de Transcrição/metabolismo , NF-kappa B/metabolismo , Ligação Proteica
3.
J Cardiothorac Vasc Anesth ; 38(4): 1045-1048, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38184381

RESUMO

The ventilatory strategy to adopt during cardiopulmonary bypass is still being debated. The rationale for using continuous positive airway pressure or mechanical ventilation would be to counteract alveolar collapse and improve ischemia phenomena and passive alveolar diffusion of oxygen. Although there are several studies supporting the hypothesis of a positive effect on oxygenation and systemic inflammatory response, the real clinical impact of ventilation during cardiopulmonary bypass is controversial. Furthermore, the biases present in the literature make the studies' results nonunique in their interpretation.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Respiração Artificial , Humanos , Respiração Artificial/métodos , Ponte Cardiopulmonar , Pulmão , Pressão Positiva Contínua nas Vias Aéreas
4.
Pediatr Cardiol ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174731

RESUMO

The gut microbiome of infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery (CPB) is at risk of profound alteration. The aim of this study was to examine the gut microbiome pre- and post-bypass surgery to explore potential implications of altered gut biodiversity. A prospective cohort study involving infants with CHD who underwent CPB was performed. Faecal samples were collected from infants alongside the collection of demographic and clinical data in order to examine gut microbiome changes before and after surgery. 16S rRNA sequencing analysis was performed on DNA isolated from stool samples to determine changes in gut microbiome composition. Thirty-three patients were recruited, with samples from thirteen of these available for final analysis. Compared with healthy, matched controls, at a genus level, pre-operative samples for infants with CHD demonstrated a higher relative abundance of Escherichia-Shigella (31% vs 2-6%) and a lower relative abundance of Bifidobacterium (13% vs 40-60%). In post-operative samples, the relative abundance of Escherichia-Shigella (35%), Enterococcus (11%), Akkermansia (6%), and Staphylococcus (5%) were higher than pre-op samples. One infant developed post-operative necrotising-enterocolitis (NEC). They displayed a marked abundance of the Enterococcus (93%) genus pre-operatively. This study demonstrates that infants with CHD have an altered gut microbiome when compared with healthy controls and there might be a possible link between an abundance of virulent species and NEC.

5.
Pain Pract ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39099243

RESUMO

OBJECTIVE: The objective of this study was to evaluate the effect of outpatient celiac plexus block on acute pain reduction in patients with suspected median arcuate ligament syndrome. METHODS: This is an Institutional Review Board approved, retrospective chart review. Data were collected and analyzed from patients who received celiac plexus blocks from November 1, 2021 through April 6, 2023. The primary outcome was pain reduction, determined by the change in numerical pain rating scale (NPRS) from pre-procedure to post-procedure. Additional data collected include patient demographics, comorbidities, preoperative symptoms and duration of symptoms. RESULTS: There were 33 patients identified in this study. Thirty-one patients were included in the data analysis. The median age of the cohort was 29 years, and the median BMI was 20.4. 94% of the cohort was female. These patients were referred as part of an evaluation for symptomatic vascular compression disorders. For many patients, positive response to celiac plexus block was used as an indication to proceed with surgical MALS resection. We provide a diagnostic algorithm for MALs. All patients endorsed preoperative symptoms. Patients experienced a median pain reduction of -4 from baseline to immediately post-procedure. CONCLUSIONS: Celiac plexus blocks continue to be a tool for ruling out neurogenic median arcuate ligament syndrome in patients who have undergone extensive previous imaging and assessments for vascular compression disorders. Our data suggest that patients with suspected MALS may experience substantial immediate pain relief from temporary blocks of the celiac ganglion as guided by fluoroscopy in an outpatient setting.

6.
Microb Pathog ; 181: 106181, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37276895

RESUMO

Clostridium perfringens (C. perfringens) beta2 (CPB2) toxin may induce necrotizing enteritis (NE) in pigs. Sirtuin1 (SIRT1) is involved in inflammatory intestinal diseases and affects intestinal barrier function. However, the effects of SIRT1 on piglet intestinal disease caused by CPB2 toxin are unclear. This study revealed the role of pig SIRT1 in CPB2 toxin-exposed intestinal porcine epithelial cells (IPEC-J2). Herein, we manifested that SIRT1 was dramatically decreased in IPEC-J2 cells infected with CPB2 toxin. Subsequently, we silenced and overexpressed SIRT1 using siRNA and a overexpression vector in CPB2 toxin-treated IPEC-J2 cells. The results indicated that overexpression of SIRT1 suppressed reactive oxygen species (ROS) generates, the expression tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and Bax, nuclear factor-kappa B (NF-κB p65), phospho (p)-NF-kB p65 and lactate dehydrogenase (LDH) activity and apoptosis in CPB2 toxin-treated IPEC-J2 cells, and increased IL-10, mitochondrial membrane potential (ΔΨm), Bcl-2, Claudin1 and Occludin levels and cell viability. These results indicated that SIRT1 protects IPEC-J2 cells against CPB2 toxin-induced oxidative damage and tight junction (TJ) disruption, which provides a theoretical basis for further study of the molecular regulatory mechanism of SIRT1 in C. perfringens-infected NE in piglets.


Assuntos
Sirtuína 1 , Toxinas Biológicas , Animais , Células Epiteliais , Intestinos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Suínos
7.
Transgenic Res ; 32(6): 497-512, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37707659

RESUMO

The potato chloroplast was transformed with codon optimized synthetic hybrid cry gene (SN19) to mitigate crop losses by Colorado potato beetle (CPB). The bombarded explants (leaves and internode) were cultured on MS medium supplemented with BAP (2.0 mg/l), NAA (0.2 mg/l), TDZ (2.0 mg/l) and GA3 (0.1 mg/l); spectinomycin 50 mg/l was used as a selection agent in the medium. Leaf explants of cultivar Kuroda induced highest percentage (92%) of callus where cultivar Santae produced the highest percentage (85.7%) of transplastomic shoots. Sante and Challenger showed 9.6% shoot regeneration efficiency followed by cultivar Simply Red (8.8%). PCR amplification yielded 16 postive transplastomic plantlets out of 21 spectinomycin resistant ones. Target gene integration was confirmed by PCR and Southern blot, whereas RT-qPCR was used to assess the expression level of transgene. The localization of visual marker gene gfp was tracked by laser scanning confocal microscopy which confirmed its expression in chloroplasts of leaf cells. The transplastomic plants ensured high mortality to both larvae and adult CPB. Foliage consumption and weight gain of CPB fed on transplastomic leaves were lower compared to the control plants. Sucessful implementation of current research findings can lead to a viable solution to CPB mediated potato losses globally.


Assuntos
Besouros , Genoma de Cloroplastos , Inseticidas , Solanum tuberosum , Animais , Besouros/genética , Inseticidas/farmacologia , Inseticidas/metabolismo , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Espectinomicina/metabolismo , Larva/genética
8.
Eur J Clin Pharmacol ; 79(11): 1425-1442, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37650923

RESUMO

PURPOSE: Investigate inhaled nitric oxide's influence on mortality rates, mechanical ventilation and cardiopulmonary bypass duration, and length of stay in the intensive care unit and hospital when administered during cardiopulmonary bypass. METHODS: Following the PRISMA guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) up to 4th March 2023. The protocol was registered in the PROSPERO database with ID: CRD42023423007. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs). RESULTS: The meta-analysis included a total of 17 studies with 2897 patients. Overall, there were no significant differences in using nitric oxide over control concerning mortality (RR = 1.03, 95% CI 0.73 to 1.45; P = 0.88) or cardiopulmonary bypass duration (MD = -0.14, 95% CI - 0.96 to 0.69; P = 0.74). The intensive care unit days were significantly lower in the nitric oxide group than control (MD = -0.80, 95% CI - 1.31 to -0.29; P = 0.002). Difference results were obtained in terms of the length of stay in the hospital according to sensitivity analysis (without sensitivity [MD = -0.41, 95% CI - 0.79 to -0.02; P = 0.04] vs. with sensitivity [MD = -0.31, 95% CI - 0.69 to 0.07; P = 0.11]. Subgroup analysis shows that, in children, nitric oxide was favored over control in significantly reducing the duration of mechanical ventilation (MD = -4.58, 95% CI - 5.63 to -3.53; P < 0.001). CONCLUSION: Using inhaled nitric oxide during cardiopulmonary bypass reduces the length of stay in the intensive care unit, and for children, it reduces the duration of mechanical ventilation.


Assuntos
Ponte Cardiopulmonar , Óxido Nítrico , Humanos , Criança , Adulto , Unidades de Terapia Intensiva , Respiração Artificial
9.
J Thromb Thrombolysis ; 56(2): 283-290, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37310666

RESUMO

Rivaroxaban is a direct factor Xa inhibitor, recently implemented as a favorable alternative to warfarin in anticoagulation therapy. Rivaroxaban effectively reduces thrombin generation, which plays a major role in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) to TAFIa. Based on the antifibrinolytic role of TAFIa, we hypothesized that rivaroxaban would consequently induce more rapid clot lysis. In vitro clot lysis assays were used to explore this hypothesis and additionally determine the effects of varying TAFI levels and a stabilizing Thr325Ile polymorphism (rs1926447) in the TAFI protein on the effects of rivaroxaban. Rivaroxaban was shown to decrease thrombin generation, resulting in less TAFI activation, thus enhancing lysis. These effects were also shown to be less substantial in the presence of greater TAFI levels or the more stable Ile325 enzyme. These findings suggest a role for TAFI levels and the Thr325Ile polymorphism in the pharmacodynamics and pharmacogenomics of rivaroxaban.


Assuntos
Carboxipeptidase B2 , Humanos , Carboxipeptidase B2/genética , Carboxipeptidase B2/farmacologia , Rivaroxabana/farmacologia , Fibrinólise , Trombina/metabolismo , Mutação
10.
Clin Exp Nephrol ; 27(4): 329-339, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36576647

RESUMO

BACKGROUND: Evaluating patients' risk for acute kidney injury (AKI) is crucial for positive outcomes following cardiac surgery. Our aims were first to select candidate risk factors from pre- or intra-operative real-world parameters collected from routine medical care and then evaluate potential associations between those parameters and risk of onset of post-operative cardiac surgery-associated AKI (CSA-AKI). METHOD: We conducted two cohort studies in Japan. The first was a single-center prospective cohort study (n = 145) to assess potential association between 115 clinical parameters collected from routine medical care and CSA-AKI (≥ Stage1) risk in the population of patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB). To select candidate risk factors, we employed random forest analysis and applied survival analyses to evaluate association strength. In a second retrospective cohort study, we targeted patients undergoing cardiac surgery with CPB (n = 619) and evaluated potential positive associations between CSA-AKI incidence and risk factors suggested by the first cohort study. RESULTS: Variable selection analysis revealed that parameters in clinical categories such as circulating inflammatory cells, CPB-related parameters, ventilation, or aging were potential CSA-AKI risk factors. Survival analyses revealed that increased counts of pre-operative circulating monocytes and neutrophils were associated with CSA-AKI incidence. Finally, in the second cohort study, we found that increased pre-operative circulating monocyte counts were associated with increased CSA-AKI incidence. CONCLUSIONS: Circulating monocyte counts in the pre-operative state are associated with increased risk of CSA-AKI development. This finding may be useful in stratifying patients for risk of developing CSA-AKI in routine clinical practice.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Humanos , Estudos de Coortes , Monócitos , Estudos Retrospectivos , Estudos Prospectivos , Ponte Cardiopulmonar/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia
11.
J Extra Corpor Technol ; 55(4): 201-205, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38099636

RESUMO

The surgical management of prosthetic valvular endocarditis (PVE) can be challenging. We report a case of a 46-year-old female patient who had a history of four cardiac operations. We chose a mitral valve replacement via right thoracotomy to enable optimal exposure of the mitral valve (MV). Because of multi-reoperations, we employed systemic hyperkalemia for cardiac arrest to protect the heart during cardiopulmonary bypass (CPB) without aortic cross-clamping. Here, we present a complex operation that performed management of CPB under hyperkalemia and the patient had a good postoperative recovery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Hiperpotassemia , Feminino , Humanos , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Toracotomia , Ponte Cardiopulmonar , Hiperpotassemia/etiologia , Hiperpotassemia/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valva Aórtica/cirurgia
12.
Int J Mol Sci ; 24(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36982798

RESUMO

Long non-coding RNAs (lncRNAs) modified by n6-methyladenosine (m6A) have been implicated in the development and progression of several diseases. However, the mechanism responsible for the role of m6A-modified lncRNAs in Clostridium perfringens type C piglet diarrhea has remained largely unknown. We previously developed an in vitro model of CPB2 toxin-induced piglet diarrhea in IPEC-J2 cells. In addition, we previously performed RNA immunoprecipitation sequencing (MeRIP-seq), which demonstrated lncRNA EN_42575 as one of the most regulated m6A-modified lncRNAs in CPB2 toxin-exposed IPEC-J2 cells. In this study, we used MeRIP-qPCR, FISH, EdU, and RNA pull-down assays to determine the function of lncRNA EN_42575 in CPB2 toxin-exposed IPEC-J2 cells. LncRNA EN_42575 was significantly downregulated at different time points in CPB2 toxin-treated cells. Functionally, lncRNA EN_42575 overexpression reduced cytotoxicity, promoted cell proliferation, and inhibited apoptosis and oxidative damage, whereas the knockdown of lncRNA EN_42575 reversed these results. Furthermore, the dual-luciferase analysis revealed that METTL3 regulated lncRNA EN_42575 expression in an m6A-dependent manner. In conclusion, METTL3-mediated lncRNA EN_42575 exerted a regulatory effect on IPEC-J2 cells exposed to CPB2 toxins. These findings offer novel perspectives to further investigate the function of m6A-modified lncRNAs in piglet diarrhea.


Assuntos
RNA Longo não Codificante , Toxinas Biológicas , Animais , Suínos , RNA Longo não Codificante/genética , Apoptose/genética , Proliferação de Células , Adenosina , Diarreia , Metiltransferases/genética
13.
Heart Lung Circ ; 32(3): 424-433, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36628657

RESUMO

BACKGROUND: Bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO) induced by cardiopulmonary bypass (CPB) are highly proteolytic and cause postoperative lung injury. Although CCL23/Myeloid progenitor inhibitory factor-1 is a human CC chemokine with potent suppressor effects on myeloid progenitor cells, in vivo inhibitory effects on BM-derived leukocyte kinetics associated with CPB are unknown. METHODS: Two-hour CPB was surgically performed in cynomolgus monkeys and BM-derived leukocytes kinetics were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Monkeys were given CCL23 (n=5) or saline (control, n=5) intravenously daily for 3 days before BrdU labelling and peripheral blood/bronchoalveolar lavage fluid (BALF) timepoint sampling to reveal BrdU-labelled cells. Levels of cytokines, CD11b, and L-selectin were considered leukocytic activation markers. RESULTS: The CCL23 treatment significantly prolonged BM transit of leukocytes (PMNs, 118.4±11.7-95.5±4.1 hours [control]; MO, 91.6±5.0-62.0±3.0 hours [control]) and reduced their alveolar appearance. The BM pool size of MO was decreased by CCL23 but PMNs were unaffected. CD11b, L-selectin expression of PMNs and MO during CPB, and post-surgical increases of interleukin (IL)-6, IL-8, TNF-α, MCP-1, and PMN elastase in the BALF were not suppressed. CONCLUSIONS: CCL23 treatment slows turnover of PMN and MO progenitors in BM and suppresses their circulatory release and lung recruitment. CCL23 has inhibitory effects specifically on the CPB-induced BM response and could hold value for preventing CPB-induced lung injury.


Assuntos
Ponte Cardiopulmonar , Lesão Pulmonar , Animais , Humanos , Bromodesoxiuridina/metabolismo , Ponte Cardiopulmonar/efeitos adversos , Quimiocinas CC , Citocinas , Isquemia , Selectina L , Leucócitos , Pulmão , Primatas/metabolismo , Macaca fascicularis
14.
Heart Lung Circ ; 32(4): 544-551, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36463076

RESUMO

AIM: Long non-coding RNA (lncRNA) can be used as a biological marker for the diagnosis and treatment of various diseases. The study aimed to detect changes in the expression of lncRNA for urothelial carcinoma associated 1 (UCA1) in patients with cardiopulmonary bypass (CPB)-induced acute respiratory distress syndrome (ARDS). Clinical values and cell function in ARDS were explored. METHOD: In total, 195 patients without CPB-induced ARDS were included in the control group, and 85 patients with ARDS were included in the ARDS group. Serum UCA1 levels were measured by quantitative real-time polymerase chain reaction. A549 was used for the cell experiments by establishing oxygen-glucose deprivation/reperfusion (OGD/R) cell models, and the cell viability and apoptosis were tested. The concentration of inflammatory factors was tested by an enzyme-linked immunosorbent assay. A luciferase reporting assay was applied for target gene analysis. RESULTS: Quantitative real-time polymerase chain reaction revealed a gradual increase in serum UCA1 in both control and ARDS cases, and patients with ARDS had higher levels of UCA1 than those in the control group. Serum UCA1 was positively correlated with serum tumour necrosis factor-α and interleukin-6 concentration in patients with ARDS. UCA1 had the ability to distinguish patients with ARDS from those without it. UCA1 inhibition protected against lung injury and inhibited cell inflammation in vitro. MicroRNA (miR-182-5p) was downregulated in OGD/R-induced cell models and sponged by UCA1. CONCLUSIONS: Elevated expression of UCA1 may be associated with the occurrence of ARDS after CPB surgery. The regulatory role of UCA1 in ARDS might be related to inflammation and downregulated miR-182-5p in alveolar epithelial cells.


Assuntos
Ponte Cardiopulmonar , MicroRNAs , RNA Longo não Codificante , Síndrome do Desconforto Respiratório , Humanos , Células A549 , Apoptose , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Ponte Cardiopulmonar/efeitos adversos , Proliferação de Células , MicroRNAs/genética , MicroRNAs/imunologia , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/imunologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia
15.
Int J Cancer ; 150(7): 1123-1133, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34817877

RESUMO

Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in noncancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64 026 controls (odds ratio [OR]: 3.80 [1.92-7.51], P = .0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases vs 77 of 64 026 gnomAD controls (OR: 2.4 [0.88-6.58], P = .087), and variants in CPB1 were detected in 5 of 1385 cases vs 33 of 64 026 controls (OR: 7.02 [2.74-18.01], P = .0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58-8.39], P < .023) and CPB1 (OR: 9.51 [3.46-26.15], P < .001). Rare variants in CPB1 and CPA1 that induce ER stress are associated with increased odds of developing pancreatic cancer.


Assuntos
Carboxipeptidase B/genética , Carboxipeptidases A/genética , Carcinoma Ductal Pancreático/etiologia , Estresse do Retículo Endoplasmático/fisiologia , Neoplasias Pancreáticas/etiologia , Carboxipeptidase B/fisiologia , Carboxipeptidases A/fisiologia , Carcinoma Ductal Pancreático/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Variação Genética , Humanos , Neoplasias Pancreáticas/genética , Risco
16.
BMC Anesthesiol ; 22(1): 122, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473580

RESUMO

BACKGROUND: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: After IRB approval, we reviewed charts of 9,518 patients who underwent cardiac surgery with CPB at three medical centers between July 2001 and June 2015. The relationship between perioperative lipid-lowering treatment and postoperative outcome was investigated. 3,988 patients who underwent CABG met inclusion criteria and were analyzed. Patients were divided into lipid-lowering or non-lipid-lowering treatment groups. RESULTS: A total of 3,988 patients were included in the final analysis. Compared to the patients without lipid-lowering medications, the patients with lipid-lowering medications had lower postoperative neurologic complications and overall mortality (P < 0.05). Propensity weighted risk-adjustment showed that lipid-lowering medication reduced in-hospital total complications (odds ratio (OR) = 0.856; 95% CI 0.781-0.938; P < 0.001); all neurologic complications (OR = 0.572; 95% CI 0.441-0.739; P < 0.001) including stroke (OR = 0.481; 95% CI 0.349-0.654; P < 0.001); in-hospital mortality (OR = 0.616; 95% CI 0.432-0.869; P = 0.006; P < 0.001); and overall mortality (OR = 0.723; 95% CI 0.634-0.824; P < 0.001). In addition, the results indicated postoperative lipid-lowering medication use was associated with improved long-term survival in this patient population. CONCLUSIONS: Perioperative lipid-lowering medication use was associated with significantly reduced postoperative adverse events and improved overall outcome in elderly patients undergoing CABG surgery with CPB.


Assuntos
Ponte de Artéria Coronária , Qualidade de Vida , Idoso , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Humanos , Lipídeos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
17.
J Cardiothorac Vasc Anesth ; 36(7): 1883-1890, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35221222

RESUMO

OBJECTIVE: To review studies that assessed systemic hypothermia as an organ protection strategy in adults undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Randomized controlled trials, irrespective of blinding, language, publication status, and date of publication, were identified by searching the Cochrane Central register of Controlled Trials, MEDLINE, and Embase until November 2020. Risk of bias assessment was performed according to Cochrane methodology. Treatment effects were expressed as risk ratios and 95% confidence intervals. Heterogeneity was expressed as I2. INTERVENTIONS: Systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Forty-eight trials enrolling 6,690 patients were included in the analysis. Methodologic quality of the studies included was low, mostly due to insufficient allocation concealment or blinding. Random-effects meta-analysis did not resolve uncertainty as to the risks and benefits for hypothermia versus normothermia for key primary and secondary outcomes, including mortality (1.21, 0.94 to 1.56, I2 = 0%) and brain injury (0.87, 0.67 to 1.14, I2 = 0%). Sensitivity analyses restricted to trials at low risk of important bias demonstrated higher mortality with hypothermia (1.70, 1.05 to 2.75, I2 = 0%), with little or no treatment effect on brain injury (1.01, 0.69 to 1.49, I2 = 0%). There was no interaction between cardioplegia temperature and the effects of cardiopulmonary bypass temperature on outcomes. There was insufficient evidence to assess the effects of hypothermia in noncoronary artery bypass graft surgery. CONCLUSION: The existing evidence for an organ-protective effect of hypothermia in adult cardiac surgery is of low quality and inconsistent.


Assuntos
Lesões Encefálicas , Procedimentos Cirúrgicos Cardíacos , Hipotermia Induzida , Hipotermia , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Humanos , Hipotermia/prevenção & controle , Hipotermia Induzida/métodos
18.
J Cardiothorac Vasc Anesth ; 36(1): 133-137, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933366

RESUMO

OBJECTIVE: To assess predictive factors of postoperative stroke in cardiac surgery using cardiopulmonary bypass (CPB). DESIGN: This study was a retrospective observational study. SETTING: This study was conducted at a single institution (Liverpool Hospital, NSW, Australia). PARTICIPANTS: All patients with CPB treated surgically at Liverpool Hospital, NSW, between January 2016 and December 2018 INTERVENTIONS: Patients underwent cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: The primary outcome was cerebrovascular accident, or stroke. Univariate and multivariate analyses via Firth's logistic regression with regard to stroke were performed. The study comprised 1,092 patients over a three-year period. In this cohort, the stroke rate was 3.1%. Via univariate analysis of factors in relation to stroke post-CPB, recent or past stroke (odds ratio [OR] 5.43 v 2.32), diabetes mellitus (OR 1.92), dialysis dependence (OR 5.67), elective procedures (OR 0.34), aortic procedures (OR 4.02), bypass and cross-clamp times (OR 1.02 and 1.04), postoperative atrial fibrillation (OR 2.28), and hypoperfusion times all reached the significance level of p ≤ 0.1 to be included in the multivariate analysis. Multivariate analysis to find independent factors in relation to stroke yielded diabetes mellitus (OR 2.49; p = 0.025), dialysis dependence (OR 3.82; p = 0.03), aortic procedures (OR 3.93; p = 0.014), and elective procedures (OR 0.24; p = 0.026) as independently predictive or protective with regard to postoperative stroke. CONCLUSIONS: Independent predictors of stroke in this single center cohort included dialysis dependence, diabetes, and aortic procedures. Elective procedures were shown to be an independent protective factor.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Acidente Vascular Cerebral , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Humanos , Razão de Chances , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
19.
Pediatr Cardiol ; 43(3): 567-579, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34694437

RESUMO

Stress caused by cardioplegic ischemic arrest was shown to alter the expression levels of heat shock proteins (Hsp), but little is known about their effects, particularly on pediatric hearts. This study aimed to investigate whether myocardial cellular stress and apoptotic response changes due to different cardioplegia (CP) solutions during cardiopulmonary bypass (CPB) in infants and to determine their influence on surgical/clinical outcomes. Therefore, twenty-seven infants for surgical closure of ventricular septal defect were randomly assigned to a CP solution: normothermic blood (BCP), delNido (dNCP), and Custodiol (CCP). Hsp levels and apoptosis were determined by immunoblotting in cardiac tissue from the right atrium before and after CP, and their correlations with cardiac parameters were evaluated. No significant change was observed in Hsp27 levels. Hsp60, Hsp70, and Hsp90 levels decreased significantly in the BCP-group but increased markedly in the CCP-group. Decreased Hsp60 and increased Hsp70 expression were detected in dNCP-group. Importantly, apoptosis was not observed in dNCP- and CCP-groups, whereas marked increases in cleaved caspase-3 and -8 were determined after BCP. Serum cardiac troponin-I (cTn-I), myocardial injury marker, was markedly lower in the BCP- and dNCP-groups than CCP. Additionally, Hsp60, Hsp70, and Hsp90 levels were positively correlated with aortic cross-clamp time, total perfusion time, and cTn-I release. Our findings show that dNCP provides the most effective myocardial preservation in pediatric open-heart surgery and indicate that an increase in Hsp70 expression may be associated with a cardioprotective effect, while an increase in Hsp60 and Hsp90 levels may be an indicator of myocardial damage during CPB.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Parada Cardíaca Induzida , Soluções Cardioplégicas , Ponte Cardiopulmonar/efeitos adversos , Criança , Proteínas de Choque Térmico/metabolismo , Humanos , Lactente , Miocárdio/metabolismo
20.
J Extra Corpor Technol ; 54(3): 250-254, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36742219

RESUMO

Interest in simulation has grown substantially, as has enthusiasm for team-based approaches to surgical training. In cardiothoracic surgery, the dynamic ability of the entire team is critical to emergent events. We developed innovative, interprofessional simulation events to improve team confidence. Two separate simulations event replicating critical steps and potential crises of cardiopulmonary bypass (CPB) were attended by members of the multidisciplinary cardiothoracic team. Standard CPB equipment, echocardiography, an app to control vital signs, and typical operating room tools for cannulation were all used. Participant started at their typical roles, then rotated into unfamiliar roles for subsequent simulations. Survey and Likert scale self-assessment tools were used to determine outcomes. Statistical analysis compared results. Two separate events were attended by a total of 37 team members (17 facilitators and 20 participants). Participants rotated roles through 12 routine and high-risk scenarios for instituting and separating from CPB. Participant evaluation results were highly favorable, with requests for further similar events. Objectively, the mean score for self-assessment rose significantly comparing the pre- and post-simulation assessments. Despite a small sample size, these differences did reach statistical significance in two categories: iatrogenic dissection (p 0.008), and emergent return to CPB (p 0.016). In our experience, high-fidelity interprofessional simulation promoted team communication and confidence for key scenarios related to institution of and separation from CPB.

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