RESUMO
We performed a large-scale flow cytometric analysis to determine whether M1 macrophage (M1Ø) and M2 macrophage (M2Ø) polarization in white adipose tissue (WAT) was altered immediately after exercise. Additionally, we comprehensively investigated the effects of obesity, exercise intensity, and recovery time on macrophage polarization in WAT. A single exercise bout of various intensities (ND, non-exercise control; -LIE, low-intensity exercise; -MIE, mid-intensity exercise; -HIE, high-intensity exercise) was performed by normal mice (ND) and obese mice (HFD). To confirm differences in M1Ø/M2Ø polarization in WAT based on the recovery time after a single exercise bout, WAT was acquired at 2 h, 24 h, and 48 h after exercise (total n = 168, 7 mice × 4 groups × 2 diets × 3 recovery time). The harvested WAT was immediately analyzed by flow cytometry, and macrophages were fluorescently labeled using F4/80, as well as M1Ø with CD11c and M2Øs with CD206. After a single bout of exercise, the M2Ø/M1Ø polarization ratio of WAT increases in both normal and obese mice, but differences vary depending on recovery time and intensity. Regardless of obesity, our findings showed that there could be a transient increase in M1Ø in WAT over a short recovery time (24 h) post-exercise (in ND-MIE, ND-HIE, and HFD-HIE). Furthermore, it was observed that the greater the exercise intensity in obese mice, the more effective the induction of M2Ø polarization immediately after exercise, as well as the maintenance of high M2Ø polarization, even after a prolonged recovery time.
RESUMO
The human calcaneus is robust and provides a prominent heel for effective bipedal locomotion, although the adjacent talus has no muscle attachments. However, there is incomplete information about the morphological changes in these prominent bones during embryo development. We examined serial histological sections of 23 human embryos and early-term fetuses (approximately 5-10 weeks' gestational age [GA]). At a GA of 5 weeks, the precartilage talus was parallel to and on the medial side of the calcaneus, which had a prolate spheroid shape and consisted of three masses. At a GA of 6 weeks, the cartilaginous talus extended along the proximodistal axis, and the tuber calcanei became long and bulky, with a small sustentaculum talus at the "distal" side. At a GA of 6 to 8 weeks, the sustentaculum had a medial extension below the talus so that the talus "rode over" the calcaneus. In contrast, the talus had a more complex shape, depending on the growth of adjacent bones. At a GA of 9 to 10 weeks, the talus was above the calcaneus, but the medial part still faced the plantar subcutaneous tissue because of the relatively small sustentaculum. Therefore, the final morphology appeared after an additional several weeks. Muscle activity seemed to facilitate growth of the tuber calcanei, but growth of the other parts of calcaneus, including the sustentaculum, seemed to depend on active proliferation at the different sites of cartilage. Multiple tendons and ligaments seemed to fix the talus so that it remained close to the calcaneus.
Assuntos
Calcâneo , Tálus , Humanos , Calcâneo/embriologia , Calcâneo/anatomia & histologia , Tálus/embriologia , Tálus/anatomia & histologia , Feto/anatomia & histologia , Feminino , Idade Gestacional , Tornozelo/anatomia & histologia , Tornozelo/embriologiaRESUMO
Recent morphometric magnetic resonance imaging (MRI) studies suggested the possibility that valproate (VPA) use is associated with parieto-occipital cortical thinning in patients with heterogeneous epilepsy syndromes. In this study, we examined the effect of VPA on the brain volume using a large number of homogenous patients with idiopathic generalized epilepsy. Voxel-based morphometry was used to compare regional gray matter (GM) volume between 112 patients currently taking VPA (VPA+ group), 81 patients not currently taking VPA (VPA- group), and 120 healthy subjects (control group). The VPA+ group showed a significant GM volume reduction in the bilateral cerebellum, hippocampus, insula, caudate nucleus, medial frontal cortex/anterior cingulate cortex, primary motor/premotor cortex, medial occipital cortex, and anteromedial thalamus, as compared to the control group. The VPA- group showed a significant GM volume reduction in the anteromedial thalamus and right hippocampus/temporal cortex, as compared to the control group. Compared to the VPA- group, the VPA+ group had a significant GM volume reduction in the bilateral cerebellum, primary motor/premotor cortex, and medial frontal cortex/anterior cingulate cortex. We have provided evidence that VPA use could result in GM volume reductions in the frontal cortex and cerebellum. Our findings should be acknowledged as a potential confounding factor in morphometric MRI studies that include subjects taking VPA.
Assuntos
Epilepsia Generalizada , Substância Cinzenta , Humanos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Ácido Valproico/efeitos adversos , Epilepsia Generalizada/patologia , Córtex Cerebral , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologiaRESUMO
INTRODUCTION: This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between maintenance therapy with two poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and niraparib, in patients with BRCA-mutated, newly diagnosed advanced epithelial ovarian cancer (EOC) who responded to platinum-based chemotherapy. METHODS: We enrolled stage III-IV EOC patients with germline and/or somatic BRCA1/2 mutations that had received maintenance therapy with olaparib or niraparib. A 3:1 propensity score matching was conducted using two variables: residual disease size and the presence of germline variants. The primary outcome was progression-free survival (PFS), and the secondary outcomes were time to first subsequent therapy (TFST), overall survival (OS), and treatment-emergent adverse events (TEAEs). RESULTS: In the propensity score-matched analysis, 80 patients who received olaparib and 31 patients who received niraparib were matched (3:1). In the propensity score-matched cohort, median PFS with olaparib vs. niraparib was not reached vs 31.5 months (HR, 1.08; 95% CI, 0.47-2.52; p = 0.854). The median TFST was not reached vs 31.8 months (HR, 1.20; 95% CI, 0.51-2.81; p = 0.682), and neither olaparib nor niraparib reached the median OS (HR, 0.42; 95% CI, 0.01-17.61; p = 0.649). In terms of the incidence rates of any-grade hematologic or non-hematologic TEAEs, higher rates of thrombocytopenia (p = 0.021) and neutropenia (p = 0.011) were observed in the niraparib group. CONCLUSION: Advanced EOC patients with BRCA1/2 mutations exhibited no significant difference in OS between olaparib and niraparib, indicating the need to consider individualized strategies for selecting PARP inhibitors based on adverse event profiles.
Assuntos
Indazóis , Neoplasias Ovarianas , Piperazinas , Piperidinas , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Quimioterapia de Manutenção , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Humanos , Feminino , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalo Livre de ProgressãoRESUMO
The aim of this study was to evaluate the safety and efficacy of digital therapeutic application of Sleep Index-Based Treatment for Insomnia (dSIBT-I) and compare them with those of digital application of Cognitive Behavioural Therapy for Insomnia (dCBT-I). This randomised prospective pilot study was conducted at the Asan Medical Center. A total of 50 patients with insomnia were recruited between December 2022 and January 2023 and randomly allocated to the dSIBT-I or dCBT-I group. The study was carried out for one month. The primary outcome was the significant reduction in Insomnia Severity Index score at Week 4 compared to baseline, while the secondary outcome was proportion of participants whose Insomnia Severity Index scores were reduced to <15 at Week 4. We performed linear mixed model and generalised estimating equation analyses. Both dSIBT-I and dCBT-I groups showed significant improvements in Insomnia Severity Index scores at Week 4. There was no significant difference between two groups in terms of Insomnia Severity Index scores at Week 4 (group × time effect, F = 1.07, p = 0.382) and proportion of participants whose Insomnia Severity Index scores were reduced to <15 at Week 4 (group × time effects, F = 1.80, p = 0.615). However, at Week 2, the dSIBT-I group showed better results than the dCBT-I group in terms of both Insomnia Severity Index scores (p = 0.044) and proportion of participants whose Insomnia Severity Index scores were reduced to <15 (82.6% vs. 48.0%, p = 0.017). No treatment-emergent adverse events were reported in either group. The dSIBT-I is a safe and effective therapy for insomnia, with rapid treatment effects.
Assuntos
Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Projetos Piloto , Resultado do Tratamento , Estudos Prospectivos , SonoRESUMO
BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.
Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Feminino , Humanos , Masculino , Neoplasias Gástricas/patologia , Herpesvirus Humano 4 , Prognóstico , Carcinoma/complicaçõesRESUMO
BACKGROUND: We aimed to investigate the efficacy and safety of repeated use of rituximab (RTX) in pediatric patients with nephrotic syndrome (NS). METHODS: Retrospective review of 50 patients with steroid-dependent NS (SDNS) who had received more than three cycles of RTX was conducted; each consisted of one to four infusions until B lymphocytes were depleted. RESULTS: The median age of starting the first RTX cycle was 12.4 years (interquartile ranges (IQR) 10.2-14.6). During a median follow-up period of 6.3 (IQR 3.6-8.6) years, patients received a median of 5.0 RTX cycles (IQR 4.0-7.3). The number of relapses decreased from a median of 2.0 relapses per year (IQR 1.0-3.0) to 0.2 relapses per year (IQR 0.0-0.5) after long-term RTX treatments (P < 0.001). Longer relapse-free periods were associated with more than four RTX cycles, longer B-cell depletion, older age at each RTX treatment, and lower cholesterol levels. B lymphocytes recovered to 1% at a median of 5.9 months (95% confidence interval 5.7-6.1) after RTX administration. Factors related to a longer period of B-cell depletion included more than five RTX cycles, a higher dose of RTX, older age at treatment, and concurrent use of antimetabolites. During repeated RTX treatments, 8.0%, 6.0%, and 2.0% of patients developed hypogammaglobulinemia, severe infection, and severe neutropenia, respectively. CONCLUSIONS: Long-term repeated use of RTX may be effective and safe in pediatric NS patients. Furthermore, the redosing of RTX could be chosen by considering predictive factors for relapse-free and B-cell depletion periods.
Assuntos
Síndrome Nefrótica , Criança , Humanos , Rituximab/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Resultado do Tratamento , Fatores de Tempo , Recidiva , Estudos Retrospectivos , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown results in slowing estimated glomerular filtration rate (eGFR) decline and reducing proteinuria in adult patients with chronic kidney disease. This retrospective study examines dapagliflozin's effects in 22 children with kidney disease and proteinuria. METHODS: Children with a median age of 15.6 years were treated with dapagliflozin for > 3 months between July 2022 and December 2023. All children had been treated with either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least 1 month before starting dapagliflozin. RESULTS: The most common kidney disease diagnoses in this study included Alport syndrome (n = 7) and medication-resistant nephrotic syndrome or focal segmental glomerulosclerosis (n = 7). After 6.1 months of treatment, dapagliflozin treatment did not result in significant changes in eGFR or proteinuria. However, at the latest follow-up, a statistically significant decrease in eGFR was noted (65.5 compared to the baseline 71.1 mL/min/1.73 m2, P = 0.003). Proteinuria remained stable between baseline and the last follow-up (final spot urine protein/creatinine ratio (uPCR) 0.7 vs. baseline uPCR 0.6 mg/mg, P = 0.489). In the subgroup analysis of children treated for > 8 months, the eGFR decline post-treatment changed from - 0.5 to - 0.2 ml/min/1.73 m2 per month (P = 0.634). Only two children discontinued dapagliflozin due to suspected adverse events. CONCLUSIONS: Dapagliflozin has not been associated with serious side effects. Further prospective clinical trials are needed to confirm the efficacy and safety of dapagliflozin in children with kidney disease.
RESUMO
Research in neuroscience often assumes universal neural mechanisms, but increasing evidence points toward sizeable individual differences in brain activations. What remains unclear is the extent of the idiosyncrasy and whether different types of analyses are associated with different levels of idiosyncrasy. Here we develop a new method for addressing these questions. The method consists of computing the within-subject reliability and subject-to-group similarity of brain activations and submitting these values to a computational model that quantifies the relative strength of group- and subject-level factors. We apply this method to a perceptual decision-making task (n = 50) and find that activations related to task, reaction time, and confidence are influenced equally strongly by group- and subject-level factors. Both group- and subject-level factors are dwarfed by a noise factor, though higher levels of smoothing increases their contributions relative to noise. Overall, our method allows for the quantification of group- and subject-level factors of brain activations and thus provides a more detailed understanding of the idiosyncrasy levels in brain activations.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Processos MentaisRESUMO
BACKGROUND: This study aimed to investigate the association between gastrectomy and endoscopic resection for gastric cancer and the subsequent tuberculosis incidence. METHODS: We conducted a nationwide matched cohort study using data from the Korea National Health Insurance Service from 2013 to 2019. We created two cohorts: patients who underwent gastrectomy and those who had endoscopic resection. Each patient was matched 1:1 with an unexposed individual based on index year, age, sex, income, and various comorbidities. The primary outcome was the incidence of tuberculosis during the follow-up period. RESULTS: Our study comprised 90,886 gastrectomy patients and 46,759 endoscopic resection patients. The tuberculosis incidence was significantly higher in the gastrectomy group compared to its matched non-gastrectomy group (IRR 1.69, 95% CI 1.43-1.99, p < .001). In contrast, there was no significant difference in tuberculosis incidence between the endoscopic resection group and its matched non-resection group (IRR 0.95, 95% CI 0.75-1.19, p = 0.627). The Kaplan-Meier cumulative incidence also did not differ between the two groups. However, tuberculosis incidence significantly increased in the first year after endoscopic resection. CONCLUSION: Gastrectomy for gastric cancer is associated with a higher incidence of subsequent tuberculosis, while no significant association was observed for endoscopic resection. However, tuberculosis incidence increases significantly during the first year after endoscopic resection.
Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Tuberculose , Humanos , Estudos de Coortes , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Endoscopia/efeitos adversos , Gastrectomia/efeitos adversos , Tuberculose/epidemiologia , Tuberculose/etiologia , Tuberculose/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ressecção Endoscópica de Mucosa/efeitos adversosRESUMO
Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.
Assuntos
Neoplasias Ovarianas , Trombose , Humanos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/metabolismo , Trombose/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Plasminogênio , Biomarcadores , HomocisteínaRESUMO
BACKGROUND: This study aimed to analyze genotype-phenotype correlations in children with Gitelman syndrome (GS). METHODS: This multicenter retrospective study included 50 Korean children diagnosed with SLC12A3 variants in one or both alleles and the typical laboratory findings of GS. Genetic testing was performed using the Sanger sequencing except for one patient. RESULTS: The median age at the diagnosis was 10.5 years (interquartile range, 6.8;14.1), and 41 patients were followed up for a median duration of 5.4 years (interquartile range, 4.1;9.6). A total of 30 different SLC12A3 variants were identified. Of the patients, 34 (68%) had biallelic variants, and 16 (32%) had monoallelic variants on examination. Among the patients with biallelic variants, those (n = 12) with the truncating variants in one or both alleles had lower serum chloride levels (92.2 ± 3.2 vs. 96.5 ± 3.8 mMol/L, P = 0.002) at onset, as well as lower serum potassium levels (3.0 ± 0.4 vs. 3.4 ± 0.3 mMol/L, P = 0.016), and lower serum chloride levels (96.1 ± 1.9 vs. 98.3 ± 3.0 mMol/L, P = 0.049) during follow-up than those without truncating variants (n = 22). Patients with monoallelic variants on examination showed similar phenotypes and treatment responsiveness to those with biallelic variants. CONCLUSIONS: Patients with GS who had truncating variants in one or both alleles had more severe electrolyte abnormalities than those without truncating variants. Patients with GS who had monoallelic SLC12A3 variants on examination had almost the same phenotypes, response to treatment, and long-term prognosis as those with biallelic variants.
Assuntos
Estudos de Associação Genética , Síndrome de Gitelman , Membro 3 da Família 12 de Carreador de Soluto , Humanos , Síndrome de Gitelman/genética , Síndrome de Gitelman/diagnóstico , Membro 3 da Família 12 de Carreador de Soluto/genética , Criança , Masculino , Estudos Retrospectivos , Feminino , Adolescente , Fenótipo , República da Coreia , Pré-Escolar , Mutação , Potássio/sangue , Predisposição Genética para Doença , Cloretos/sangueRESUMO
Life-threatening airway obstruction is a major concern in patients with Pierre-Robin sequence. Tongue-lip adhesion (TLA) has been used to manage airway obstruction. The authors present the case of a female neonate with Pierre-Robin sequence who presented with airway obstruction and a cleft palate. She underwent a TLA procedure with modified tongue base suspension (TBS). Endoscopy was used to check and control the traction of the tongue base to enable unobstructed self-ventilation. Positive outcomes including improved O2 saturation and weight gain were noted. The effectiveness of TLA was enhanced by using TBS with real-time endoscopy to evaluate the oropharyngeal airway space required to alleviate airway obstruction. The use of endoscopy enabled us to check and determine how much the tongue base should be tracted by manipulating the tongue anteriorly and posteriorly. The authors report transoral endoscopy-assisted TLA and modified TBS.
Assuntos
Obstrução das Vias Respiratórias , Laringe , Síndrome de Pierre Robin , Recém-Nascido , Humanos , Feminino , Síndrome de Pierre Robin/cirurgia , Língua/cirurgia , Endoscopia , Resultado do TratamentoRESUMO
Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.
Assuntos
Ascomicetos , Magnaporthe , Oryza , Magnaporthe/fisiologia , Melhoramento Vegetal , Proteínas/metabolismo , Resistência à Doença/genética , Proteínas de Repetições Ricas em Leucina , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: There is currently no information on positional changes in the brachial nerve plexus during prenatal growth. The subclavian-axillary artery passing through the medianus nerve ansa is considered a good landmark for evaluating the height of the plexus. MATERIALS AND METHODS: We used histologic sections from 9 embryos and 17 fetuses (approximately 6-15 weeks of gestational age) to identify the height of the ansa by referring to the level of the rib and the glenohumeral joint. RESULTS: The nerve ansa was usually (23 plexuses) observed at the level of the first and/or second ribs. However, it was sometimes observed above the first rib, at a distance equal to or more than an intercostal width (7 plexuses). In the latter group, the ansa was usually located below the glenohumeral joint. Thus, the joint was located higher than the first rib, although the upper extremities were in the anatomic position for all specimens. The left-right difference in the height of the plexus corresponded to or was less than the width of the first intercostal space. Despite the synchronized growth between the thorax and shoulder girdle, the brachial plexus showed a considerable variation in comparative height; the range corresponded to twice of an intercostal width. Whether the nerve plexus is located high or low is determined at an early developmental stage and is maintained during the later growth stages. CONCLUSION: The high-positioned plexus might cause nerve injury at delivery, followed by a glenohumeral joint deformity because of the fragility without fixation in the thorax.
Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Parede Torácica , Humanos , Ombro , Plexo Braquial/lesões , Extremidade Superior , FetoRESUMO
BACKGROUND: There is no information about muscle growth in eyelids with infrequent blinking in fetuses. METHODS: To examine the muscle and nerve morphology, we morphometrically and immunohistochemically examined sagittal sections of unilateral upper eyelids obtained from 21 term fetuses (approximately 30-42 weeks of gestation) and, for the comparison, those from 10 midterm fetuses (12-15 weeks). RESULTS: The approximation margin of the upper eyelid always corresponded to the entire free margin in midterm fetuses, whereas it was often (18/21) restricted in the posterior part in term fetuses. Thus, in the latter, the thickness at the approximation site to the lower lid often ranged from 0.8 to 1.6 mm and corresponded to 18-56% of the nearly maximum thickness of the lid. In the lower part of the upper eyelid, a layer of the orbicularis oculi muscles often (14/21) provided posterior flexion at 90-120° to extend posteriorly. Nerve fibers running along the mediolateral axis were rich along the approximation surface at term, but they might not be reported in the upper eyelid of adults. CONCLUSION: Being different from adult morphologies, the term eyelid was much thicker than the approximation surface and it carried a flexed muscle layer and transversely-running nerve. The infrequent blinking in fetuses seemed to provide a specific condition for the muscle-nerve growth. Plastic and pediatric surgeons should pay attention to a fact that infants' upper eyelid was unlikely to be a mini-version of the adult morphology.
Assuntos
Pálpebras , Corrida , Adulto , Criança , Humanos , Pálpebras/anatomia & histologia , Piscadela , Músculos Faciais/inervação , Feto , Músculos OculomotoresRESUMO
BACKGROUND: Air pollution-induced systemic inflammation and oxidative stress are hypothesized to be the major biological mechanisms underlying pathological outcomes. We examined the association between short-term exposure to ambient air pollutants and biomarkers of inflammation and oxidative stress in 2199 general middle-aged Korean population residing in metropolitan areas. METHODS: Serum levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. Daily concentrations of a series of air pollutants (particulate matter [PM]10, PM2.5, SO2, NO2, CO, and O3) were predicted using the Community Multiscale Air Quality modeling system, and participant-level pollutant exposure was determined using geocoded residential addresses. Short-term exposure was defined as the 1- to 7-day moving averages. RESULTS: The multivariable-adjusted linear models controlling for the sociodemographic, lifestyle, temporal, and meteorological factors identified positive associations of PM with IL-1ß, IL-8, IL-10, TNF-α, and 8-OHdG levels; SO2 with IL-10 levels, CO with IL-1ß, IL-10, and TNF-α levels; and O3 with IL-1ß, IL-8, and 8-OHdG levels. O3 levels were inversely associated with IL-10 levels. For each pollutant, the strongest associations were observed for the 7-day average PM and CO with IL-1ß (per 10-µg/m3 increase in PM10: 2.7%, 95% confidence interval [CI] = 0.6-4.8; per 10-µg/m3 increase in PM2.5: 6.4%, 95% CI = 2.4-10.5; per 0.1-ppm increase in CO: 3.3%, 95% CI = 0.3-6.5); the 2-day average SO2 with IL-10 levels (per 1-ppb increase in SO2: 1.1%, 95% CI = 0.1-2.1); and the 7-day average O3 with IL-8 levels (per 1-ppb increase in O3: 1.3%, 95% CI = 0.7-1.9). CONCLUSIONS: Short-term exposure to ambient air pollutants may induce oxidative damage and pro-inflammatory roles, together with counter-regulatory anti-inflammatory response.
Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Pessoa de Meia-Idade , Humanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Estudos Transversais , Interleucina-10 , Interleucina-8 , Fator de Necrose Tumoral alfa , Material Particulado/efeitos adversos , Material Particulado/análise , Inflamação/induzido quimicamente , Inflamação/epidemiologia , Biomarcadores , Estresse OxidativoRESUMO
BACKGROUND: Adenovirus expresses two non-coding virus-associated (VA) RNAs: VA I RNA and VA II RNA. Adenovirus-expressed VA RNAs interfere with the microRNA (miRNA) pathway by competing with precursor miRNAs. The processing pattern of primary miRNA (pri-miRNA) and factors to affect its processing are not exactly known when using adenovirus for the delivery of pri-miRNA. METHODS: To observe pri-miRNA processing, plasmid construct encoding pri-miRNA was co-transfected with VA I/II RNA expression plasmid, or recombinant adenovirus encoding pri-miRNA was generated and infected. Levels of miRNAs, VA I RNA and VA II RNA were analyzed by a quantitative real-time PCR (RT-PCR). VA I-II full-length RNA was analyzed by a RT-PCR. RNA immunoprecipitation analysis to pull-down the VA I-II full-length RNA binding with Drosha was conducted with Drosha antibody. RESULTS: pri-miRNA was normally processed into mature miRNA when it was expressed in cells using plasmid. However, miRNA maturation was impaired when pri-miRNA was delivered and expressed using adenovirus. Of note, pri-miRNA processing was observed to be blocked by VA RNA expression. Such blocked processing could be recovered by introducing antisense RNA of VA RNA, anti-3'VA RNA. In addition, VA RNAs were transcribed into VA I-II full-length RNA, which was found to bind and sequester Drosha. CONCLUSIONS: Adenovirus infection downregulated the processing of pri-miRNAs in cells, and such downregulation could be derived from VA I-II full-length RNAs in pri-miRNA-like form through competitively binding to Drosha protein. These results indicated that the expression of adenovirus VA RNAs should be inhibited for successful delivery and expression of pri-miRNA or shRNA in cells using adenovirus.
Assuntos
MicroRNAs , Processamento Pós-Transcricional do RNA , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Adenoviridae/genéticaRESUMO
BACKGROUND: To evaluate the cost-effectiveness of the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) following interval cytoreductive surgery (ICS) for stage III-IV ovarian cancer from a randomized controlled phase III trial. METHODS: A comparative cost-effective analysis was performed using a Markov health-state transition model derived from the current trial cohort (ClinicalTrials.gov Identifier: NCT01091636). The incremental cost-effectiveness ratio (ICER) was evaluated by dividing the incremental costs by incremental quality-adjusted life-years (QALYs) with a time horizon of 10 years. Costs were calculated from the perspective of Korean healthcare, and health utility values were extracted from published sources. RESULTS: Based on data from the trial, the mean QALY in the ICS group was 7.16 compared to 10.8 in ICS followed by the HIPEC group. With an incremental QALY of 3.64, the ICS followed by HIPEC, was estimated to obtain an ICER of KRW 954,598 (USD 708.3) per QALY. CONCLUSION: The findings of the study suggest that ICS followed by HIPEC, is cost-effective with a significant gain in QALYs. These results may support the current reimbursement of HIPEC from Korean insurance services and the management of long-term conditions.