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Epitranscriptomic RNA modifications have emerged as important regulators of the fate and function of viral RNAs. One prominent modification, the cytidine methylation 5-methylcytidine (m5C), is found on the RNA of HIV-1, where m5C enhances the translation of HIV-1 RNA. However, whether m5C functionally enhances the RNA of other pathogenic viruses remains elusive. Here, we surveyed a panel of commonly found RNA modifications on the RNA of hepatitis B virus (HBV) and found that HBV RNA is enriched with m5C as well as ten other modifications, at stoichiometries much higher than host messenger RNA (mRNA). Intriguingly, m5C is mostly found on the epsilon hairpin, an RNA element required for viral RNA encapsidation and reverse transcription, with these m5C mainly deposited by the cellular methyltransferase NSUN2. Loss of m5C from HBV RNA due to NSUN2 depletion resulted in a partial decrease in viral core protein (HBc) production, accompanied by a near-complete loss of the reverse transcribed viral DNA. Similarly, mutations introduced to remove the methylated cytidines resulted in a loss of HBc production and reverse transcription. Furthermore, pharmacological disruption of m5C deposition led to a significant decrease in HBV replication. Thus, our data indicate m5C methylations as a critical mediator of the epsilon elements' function in HBV virion production and reverse transcription, suggesting the therapeutic potential of targeting the m5C methyltransfer process on HBV epsilon as an antiviral strategy.
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Citidina , Vírus da Hepatite B , RNA Viral , Transcrição Reversa , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , RNA Viral/genética , RNA Viral/metabolismo , Citidina/análogos & derivados , Citidina/metabolismo , Citidina/genética , Humanos , Transcrição Reversa/genética , Metilação , Replicação Viral/genética , Epigênese Genética , Vírion/metabolismo , Vírion/genética , TranscriptomaRESUMO
The prevalence of overweight and obesity is increasing, leading to metabolic-associated fatty liver disease (MAFLD) characterized by excessive accumulation of liver fat and a risk of developing hepatocellular carcinoma (HCC). The driver gene mutations may play the roles of passengers that occur in single 'hotspots' and can promote tumorigenesis from benign to malignant lesions. We investigated the impact of high body weight and BMI on HCC survival using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. To explore the effects of obesity-related gene mutations on HCC, we collected driver mutation genes in 34 TCGA patients with BMI ≥ 27 and 23 TCGA patients with BMI < 27. The digital PCR performing the PBMC samples for the variant rate by clinical cohort of 96 NAFLD patients. Our analysis showed that obesity leads to significantly worse survival outcomes in HCC. Using cbioportal, we identified 414 driver mutation genes in patients with obesity and 127 driver mutation genes in non-obese patients. Functional analysis showed that obese-related genes significantly enriched the regulated lipid and insulin pathways in HCC. The insulin secretion pathway in patients with obesity HCC-specific survival identified ABCC8 and PRKCB as significant genes (p < 0.001). It revealed significant differences in gene mutation and gene expression profiles compared to non-obese patients. The digital PCR test ABCC8 variants were detected in PBMC samples and caused a 14.5% variant rate, significantly higher than that of non-obese NAFLD patients. The study findings showed that the gene ABCC8 was a patient with the obesity-related gene in NAFLD, which provides the probability that ABCC8 mutation contributes to the pre-cancer lesion biomarker for HCC.
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Hepatocellular carcinoma (HCC) is among the most prevalent visceral neoplasms. So far, reliable biomarkers for predicting HCC recurrence in patients undergoing surgery are far from adequate. In the aim of searching for genetic biomarkers involved in HCC development, we performed analyses of cDNA microarrays and found that the DNA repair gene NEIL3 was remarkably overexpressed in tumors. NEIL3 belongs to the Fpg/Nei protein superfamily, which contains DNA glycosylase activity required for the base excision repair for DNA lesions. Notably, the other Fpg/Nei family proteins NEIL1 and NEIL2, which have the same glycosylase activity as NEIL3, were not elevated in HCC; NEIL3 was specifically induced to participate in HCC development independently of its glycosylase activity. Using RNA-seq and invasion/migration assays, we found that NEIL3 elevated the expression of epithelial-mesenchymal transition (EMT) factors, including the E/N-cadherin switch and the transcription of MMP genes, and promoted the invasion, migration, and stemness phenotypes of HCC cells. Moreover, NEIL3 directly interacted with the key EMT player TWIST1 to enhance invasion and migration activities. In mouse orthotopic HCC studies, NEIL3 overexpression also caused a prominent E-cadherin decrease, tumor volume increase, and lung metastasis, indicating that NEIL3 led to EMT and tumor metastasis in mice. We further found that NEIL3 induced the transcription of MDR1 (ABCB1) and BRAF genes through the canonical E-box (CANNTG) promoter region, which the TWIST1 transcription factor recognizes and binds to, leading to the BRAF/MEK/ERK pathway-mediated cell proliferation as well as anti-cancer drug resistance, respectively. In the HCC cohort, the tumor NEIL3 level demonstrated a high positive correlation with disease-free and overall survival after surgery. In conclusion, NEIL3 activated the BRAF/MEK/ERK/TWIST pathway-mediated EMT and therapeutic resistances, leading to HCC progression. Targeted inhibition of NEIL3 in HCC individuals with NEIL3 induction is a promising therapeutic approach. © 2022 The Pathological Society of Great Britain and Ireland.
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Carcinoma Hepatocelular , DNA Glicosilases , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , DNA Glicosilases/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de Sinais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fatores de Transcrição Twist/metabolismoRESUMO
OBJECTIVE: Difficult airway situations, such as trismus and neck rigidity, may prohibit standard midline orotracheal intubation. An alternative route of intubation from the retromolar space using a fiberoptic scope or rigid intubation stylet has been reported. There is no study investigating the applicability of retromolar intubation using a video intubating stylet. This study comparatively analyzed difficult airway management using a video intubating stylet in the retromolar and standard midline approaches. METHODS: A randomized crossover manikin study was conducted between January 2021 and June 2021 at a tertiary teaching hospital. Thirty-six emergency medicine residents and attending physicians were enrolled, and all participated in an educational course regarding video intubating stylet in standard midline and retromolar approaches. Then, they performed both intubation approaches in a randomized order on a manikin seven times with different airway settings each time. The duration of successful intubation, first attempt success rate, overall success rate, number of attempts, and self-reported difficulty were recorded and compared. RESULTS: Thirty-six emergency physicians were included in the study. Compared with the standard midline approach, the use of the retromolar approach significantly reduced the duration of successful intubation in difficult airway scenarios such as limited mouth opening and neck rigidity with (44.77 [28.58-63.65] vs. 120 [93.86-120] s, p < 0.001) and without tongue edema (31.5 [22.57-57.74] vs. 44.72 [36.23-65.34] s, p = 0.012). Furthermore, the retromolar approach increased the first attempt success rate in scenarios of limited mouth opening and neck rigidity with (91.67% vs. 16.67%, p < 0.001) and without (97.22% vs. 72.22%, p = 0.012) tongue edema. The self-reported difficulty was also significantly lower with the retromolar approach than with the standard approach in the above two scenarios. CONCLUSIONS: The retromolar approach for intubation using a video intubating stylet may be a promising choice for selected patients with a combination of difficult airway features such as limited mouth opening, neck rigidity, and edematous tongue.
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Laringoscópios , Doenças da Língua , Manuseio das Vias Aéreas , Estudos Cross-Over , Edema , Humanos , Intubação Intratraqueal , Laringoscopia , Manequins , Gravação em VídeoRESUMO
Hemorrhagic stroke is a serious clinical condition that requires timely diagnosis. An artificial intelligence algorithm system called DeepCT can identify hemorrhagic lesions rapidly from non-contrast head computed tomography (NCCT) images and has received regulatory clearance. A non-controlled retrospective pilot clinical trial was conducted. Patients who received NCCT at the emergency department (ED) of Kaohsiung Veteran General Hospital were collected. From 2020 January-1st to April-30th, the physicians read NCCT images without DeepCT. From 2020May-1st to August-31st, the physicians were assisted by DeepCT. The length of ED stays (LOS) for the patients was collected. 2,999 patients were included (188 and 2811 with and without ICH). For patients with a final diagnosis of ICH, implementing DeepCT significantly shortened their LOS (560.67 ± 604.93 min with DeepCT vs. 780.83 ± 710.27 min without DeepCT; p = 0.0232). For patients with a non-ICH diagnosis, the LOS did not significantly differ (705.90 ± 760.86 min with DeepCT vs. 679.45 ± 681.97 min without DeepCT; p = 0.3362). For patients with ICH, those assisted with DeepCT had a significantly shorter LOS than those without DeepCT. For patients with a non-ICH diagnosis, implementing DeepCT did not affect the LOS, because emergency physicians need same efforts to identify the underlying problem(s) with or without DeepCT. In summary, implementing DeepCT system in the ED will save costs, decrease LOS, and accelerate patient flow; most importantly, it will improve the quality of care and increase the confidence and shorten the response time of the physicians and radiologists.
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Inteligência Artificial , Aprendizado Profundo , Serviço Hospitalar de Emergência , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Projetos Piloto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Surgery-related isolated proximal median neuropathy is a rare complication. Brachial plexus injury is a possible complication after major cardiac surgery; however, isolated mononeuropathy is less frequently documented. We present an unusual case of isolated proximal median neuropathy after aortic dissection repair surgery in a 39-year-old man. Electrodiagnostic study and ultrasound examinations helped in localizing the lesion to the axillary region. Serial follow-ups showed improvement in electrodiagnostic parameters, which were compatible with clinical symptoms. Partial recovery was achieved at the seventh month follow-up. This case report aimed to increase awareness of nerve stretching during open heart surgery and demonstrate the diagnosis and clinical follow-up by concomitant use of electrodiagnostic and nerve ultrasound studies.
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Dissecção Aórtica , Plexo Braquial , Neuropatia Mediana , Adulto , Dissecção Aórtica/cirurgia , Humanos , Masculino , UltrassonografiaRESUMO
The receptor for advanced glycation end products (RAGE) overexpression was suggested to be associated with prostate cancer development and poor prognosis. In this study, we focused on the correlations between the clinicopathological characteristics and susceptibility of prostate cancer and RAGE single-nucleotide polymorphisms (SNPs). In 579 prostate cancer patients, the RAGE SNPs rs1800625, rs1800624, rs2070600 and rs184003 in patients with or without grade group upgrade were analysed with real-time polymerase chain reaction. The results demonstrated that the prostate cancer patients who carried the RAGE SNPs rs2070600 'GA' genotypic variants were significantly associated with lower risk to develop grade group upgrade. Moreover, patients with the RAGE rs1800625 'TC + CC' genotypic variants were associated with higher risk of perineural invasion. In 343 prostate cancer patients who carried the RAGE rs1800625 'TC + CC' genotype without grade group upgrade were correlated with higher risk of biochemical recurrence and perineural invasion. In the analysis of TCGA database, significant differences of the RAGE mRNA level were found between the normal controls and prostate cancer patients (p < 0.0001), and the pathologic stage N1 and N0 patients (p = 0.0027). The prostate cancer patients with high RAGE expression were associated with lower overall survival rate (p = 0.025). In conclusion, our results have revealed that the RAGE SNPs rs2070600 and rs1800625 were associated with the grade group upgrade of prostate cancer and clinical status. The RAGE polymorphisms may provide as a pivotal predictor to evaluate prostate cancer disease progression and prognosis.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Receptor para Produtos Finais de Glicação Avançada/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Neoplasias da Próstata/mortalidade , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
BACKGROUND: Ascending aortic thrombus (AAT) in a nonaneurysmal aorta is an extremely rare event and has potentially catastrophic complications, with a life-threatening risk of myocardial infarction and cerebral embolization. This systematic review aims to elucidate the clinical manifestations and to compare the outcomes of anticoagulation therapy versus open aortic surgery for AAT. METHODS: The MEDLINE/PubMed databases were extensively searched between 1995 and 2019. All relevant publications on AAT in adults were reviewed, and individual patient data were pooled in this meta-analysis. The primary outcome was AAT resolution. The adverse outcome variables were recurrent arterial embolic events, complications related to open aortic surgery, and mortality during the study period. Chi-squared test and logistic regression analysis were used to compare groups and identify any predictors of mortality. RESULTS: Overall, 107 patients from 101 articles were included, of whom 29 patients who received anticoagulation therapy and 59 who underwent open aortic surgery were included in the outcome analysis. Among 29 patients treated with initial anticoagulation therapy, the persistence of AAT was observed in 11 patients (38%) and recurrent arterial embolization was developed in 6 patients (21%). All 11 patients in the anticoagulation group underwent secondary aortic surgery for the persistence of AAT with uneventful postoperative course. Compared with patients treated with primary aortic surgery, patients treated with initial anticoagulation therapy had higher risk of recurrent embolization (P = 0.002). No significant difference existed in the mortality rates between the groups (P = 0.106). Hemodynamic instability was an independent predictor of mortality (P = 0.008). CONCLUSIONS: Anticoagulation therapy and open aortic surgery for AAT show similar results; however, open aortic surgery reliably removes AAT and reduces the risk of recurrent embolization compared with anticoagulation therapy. Furthermore, the preoperative hemodynamic status significantly influences the clinical outcome and is a strong predictor of prognosis.
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Anticoagulantes/uso terapêutico , Aorta/cirurgia , Doenças da Aorta/terapia , Fibrinolíticos/uso terapêutico , Trombose/terapia , Procedimentos Cirúrgicos Vasculares , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/mortalidade , Doenças da Aorta/fisiopatologia , Feminino , Fibrinolíticos/efeitos adversos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recidiva , Medição de Risco , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/mortalidade , Trombose/fisiopatologia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
BACKGROUND: The aim of this study is to present our experience of thoracic endovascular aortic repair (TEVAR) for type A intramural hematoma (TAIMH) and retrograde thrombosed type A aortic dissection (rt-TAAD) with the entry tear in the descending aorta or the abdominal aorta and discuss the outcomes. METHODS: We retrospectively reviewed total 6 patients who underwent TEVAR for TAIMH (n = 2) or rt-TAAD (n = 4) in our hospital between September 2017 and July 2019. The mean age of the patients (5 men and 1 woman) was 74 ± 13 years, and the mean follow-up duration was 13 ± 7 months. RESULTS: TEVAR was successfully performed in the acute phase in all patients without relevant complications. After TEVAR, the shrinkage of enlarged thoracic aorta and complete resorptions of the false lumen of the entire thoracic aorta were achieved in 4 patients. In the remaining 2 patients, one had residual thrombosed false lumen of the ascending aorta due to a new development of PAU at the distal aortic arch and another needed additional endovascular intervention for ascending aorta hematoma progression. Late aorta-related adverse event was observed in one patient, who needed open aortic repair. There was no death during follow-up. CONCLUSIONS: Tear-oriented endovascular aortic repair is a potential option in selected patients of TAIMH and rt-TAAD and has shown favorable immediate outcomes and aortic remodeling. However, the late aorta-related adverse event is not negligible, and their long-term outcome has not been fully clarified. More research is warranted.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Hematoma/cirurgia , Trombose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Hematoma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Stents , Trombose/diagnóstico por imagem , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: To investigate the association between specific dental therapy for periodontal disease and the risk of ischaemic stroke. MATERIALS AND METHODS: We conducted a population-based cohort study that used data from the Taiwan National Health Insurance Research Database 2005 for the period of 2000-2013. Our observations focused on patients with the diagnoses of gingivitis or periodontitis with and without specific treatment and subsequent incidence of ischaemic stroke. Dental care services include dental scaling, intensive treatment (subgingival curettage and root planing) and tooth extraction. Multivariate Cox regression analysis was used to estimate the hazard ratios and corresponding 95% confidence intervals (95% CI). RESULTS: Compared with those in the gingivitis cohort, patients with periodontitis have a higher risk of ischaemic stroke and a lower survival rate of stroke over the 10-year follow-up period. After integrative dental care, both dental scaling and intensive treatment, the risk was reduced, especially in patients with periodontitis, while patients with periodontal disease may have an increased risk of stroke after tooth extraction therapy. CONCLUSIONS: Our study showed that periodontitis is a risk factor for ischaemic stroke. Both dental scaling and intensive treatment for periodontal disease are associated with a lower risk of further ischaemic stroke events.
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Isquemia Encefálica , Doenças Periodontais , Acidente Vascular Cerebral , Estudos de Coortes , Assistência Odontológica , Raspagem Dentária , Humanos , Estudos Retrospectivos , TaiwanRESUMO
Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti-inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP-2 and/or MMP-9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 µM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 µM naringenin. Zymography analysis also revealed that the activities of MMP-2 and MMP-9 of GBM cells were significantly inhibited in response to 100, 200, or 300 µM naringenin treatment. Proteins of MMP-2 and MMP-9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.
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Neoplasias Encefálicas/fisiopatologia , Movimento Celular/efeitos dos fármacos , Flavanonas/farmacologia , Glioblastoma/fisiopatologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade NeoplásicaRESUMO
OBJECTIVE: The aim of this study was to investigate the pattern of ergotamine prescription and overuse in Taiwan. BACKGROUND: Ergotamine is a frequently prescribed medication for the treatment of migraine, although excessive use may lead to medication-overuse headache. METHODS: We conducted a retrospective cohort study by using the Longitudinal Health Insurance Database 2005 in Taiwan. Patients enrolled in the study were between the ages of 18 and 80 years, received at least two prescriptions of ergotamine, and follow-up for more than 1 year at outpatient clinics during 1999 to 2013. Each ergotamine prescription was converted into a defined daily dose (DDD) and patients were sorted into two groups: occasional users, having fewer than 3 consecutive months of use, and regular users, with 3 consecutive months of use or more. Regular users were further divided into overusers (DDDs ≥ 10 per month) and non-overusers. RESULTS: A total of 41,023 migraine patients were enrolled in the study; 5803 patients were classified as regular users, with 859 of those being overusers. Of the ergotamine overusers, around 698/859 (82%) continued to use, and 443/859 (52%) remained overusers of ergotamine in the subsequent year after the index date. The most frequently prescribed prophylactic medications were propranolol and flunarizine, which were prescribed in 30.4% and 20.0% of overuse patients, respectively. CONCLUSIONS: Ergotamine overuse remains common in Taiwan, while prophylactic medicine is still underutilized. More education on ergotamine-overuse headache is needed to improve awareness.
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Ergotamina/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Uso Excessivo de Medicamentos Prescritos , Vasoconstritores/uso terapêutico , Adulto , Ergotamina/efeitos adversos , Feminino , Seguimentos , Transtornos da Cefaleia Secundários/epidemiologia , Transtornos da Cefaleia Secundários/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Uso Excessivo de Medicamentos Prescritos/tendências , Estudos Retrospectivos , Taiwan/epidemiologia , Vasoconstritores/efeitos adversosRESUMO
Biomaterials are often added to autologous fat grafts both as supporting matrices for the grafted adipocytes and as cell carrier for adipose-derived stem cells (ADSCs). This in vivo study used an autologous fat graft model to test a lamininalginate biomaterial, adipocytes, and ADSCs in immune-competent rats. We transplanted different combinations of shredded autologous adipose tissue [designated "A" for adipose tissue]), laminin-alginate beads [designated "B" for bead], and ADSCs [designated "C" for cell]) into the backs of 15 Sprague-Dawley rats. Group A received only adipocytes, Group B received only laminin-alginate beads, Group AB received adipocytes mixed with laminin-alginate beads, Group BC received laminin-alginate beads encapsulating ADSCs, and Group ABC received adipocytes and laminin-alginate beads containing ADSCs. Seven-tesla magnetic resonance imaging was used to evaluate the rats at the 1st, 6th, and 12th weeks after transplantation. At the 12th week, the rats were sacrificed and the implanted materials were retrieved for gross examination and histological evaluation. The results based on MRI, gross evaluation, and histological data all showed that implants in Group ABC had better resorption of the biomaterial, improved survival of the grafted adipocytes, and adipogenic differentiation of ADSCs. Volume retention of grafts in Group ABC (89%) was also significantly greater than those in Group A (58%) (p < 0.01). Our findings support that the combination of shredded adipose tissue with ADSCs in laminin-alginate beads provided the best overall outcome.
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Adipócitos/citologia , Tecido Adiposo/transplante , Alginatos/química , Materiais Biocompatíveis/química , Laminina/química , Células-Tronco/citologia , Adipogenia , Animais , Sobrevivência Celular , Feminino , Imageamento por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
This work presents a series of novel quinoidal organic semiconductors based on diselenophene-dithioalkylthiophene (DSpDST) conjugated cores with various side-chain lengths (-thiohexyl, -thiodecyl, and -thiotetradecyl, designated DSpDSTQ-6, DSpDSTQ-10, and DSpDSTQ-14, respectively). The purpose of this research is to develop solution-processable organic semiconductors using dicyanomethylene end-capped organic small molecules for organic field effect transistors (OFETs) application. The physical, electrochemical, and electrical properties of these new DSpDSTQs are systematically studied, along with their performance in OFETs and thin film morphologies. Additionally, the molecular structures of DSpDSTQ are determined through density functional theory (DFT) calculations and single-crystal X-ray diffraction analysis. The results reveal the presence of intramolecular S (alkyl)···Se (selenophene) interactions, which result in a planar SR-containing DSpDSTQ core, thereby promoting extended π-orbital interactions and efficient charge transport in the OFETs. Moreover, the influence of thioalkyl side chain length on surface morphologies and microstructures is investigated. Remarkably, the compound with the shortest thioalkyl chain, DSpDSTQ-6, demonstrates ambipolar carrier transport with the highest electron and hole mobilities of 0.334 and 0.463 cm2 V-1 s-1 , respectively. These findings highlight the excellence of ambipolar characteristics of solution-processable OFETs based on DSpDSTQs even under ambient conditions.
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Background: Few studies have studied the efficacy of using immersive virtual reality (iVR) to teach surgical skills, especially by using real-world iVR recordings rather than simulations. This study aimed to investigate whether viewing 360° iVR instructional recordings produces greater improvements in basic suturing skills of students without prior medical training, beyond traditional methods like reading written manuals or watching 2D instructional videos. Materials and methods: This was a partially blinded randomized cohort study. 44 pre-university students (aged 17) were randomized equally to either the written instruction manual, 2D instructional video, or iVR recordings. All students first watched a silent 2D demonstration video of the suturing task, before attempting to place three simple interrupted sutures on a piece of meat as a baseline. The time taken for the first attempt was recorded. Students were then given an hour to train using their allocated modality. They attempted the suturing task again, and timings were re-recorded. Four blinded surgically-trained judges independently assessed the quality of the stitches placed both pre and post-intervention. One-way analysis of variance tests (ANOVAs) and independent two-sample t-tests were used to determine the effect of training modality on improvements in suturing scores and time taken to complete suturing from pre to post-training. Results: For suturing scores, the iVR group showed significantly larger score improvements than the Written Manual group (p = 0.031, Cohen's D = 0.92), while this iVR advantage was less pronounced when compared with the 2D Video group (p = 0.16, Cohen's D = 0.65). Similarly for time taken to complete suturing, the iVR group had significantly larger time improvements than the Written Manual group (p = 0.045), although this difference was less robust compared to the 2D Instructional Video group (p = 0.34). Conclusion: This study demonstrates that iVR training using real-world 360° instructional recordings produced significantly greater training gains in suturing scores and efficiency compared to reading written text. iVR training also led to larger training gains in both outcome measures than viewing 2D instructional videos, although the differences between them did not reach statistical significance.
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Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S(2) mutant large HBV surface antigen (LHBS) in type II ground glass hepatocytes (GGHs) has been recognized as an emerging viral oncoprotein; it directly interacts with the c-Jun activation domain-binding protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor-suppressor retinoblastoma and, consequently, leads to disturbed cell cycle progression. The interaction of the pre-S(2) mutant LHBS with JAB1 could provide a potential target for chemoprevention. In this study, we found that the preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent kinase inhibitor p27(Kip1), which serves as a marker for pre-S(2) mutant-JAB1 complex formation. The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) elevated expression of the tumor-suppressor thioredoxin-binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction and abolished the pre-S(2) mutant LHBS-induced degradation of p27(Kip1), which, in turn, recovered the normal cell cycle checkpoint. The pre-S(2) mutant LHBS-induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic ratio and proliferating cell nuclear antigen expression, were all greatly ameliorated after SAHA treatments, which suggested SAHA as a promising chemopreventive agent for the pre-S(2) mutant oncoprotein-induced HCC. In conclusion, this study provides the mechanism of histone deacetylase (HDAC) inhibitor in preventing the pre-S(2) mutant-induced oncogenic phenotype. The HDAC inhibitor SAHA is therefore a potential chemopreventive agent for high-risk chronic HBV patients who may develop HCC.
Assuntos
Carcinoma Hepatocelular/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/metabolismo , Hepatite B Crônica/prevenção & controle , Ácidos Hidroxâmicos/farmacologia , Neoplasias Hepáticas/prevenção & controle , Mutação/genética , Precursores de Proteínas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Complexo do Signalossomo COP9 , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Feminino , Imunofluorescência , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Precursores de Proteínas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/genética , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , Técnicas do Sistema de Duplo-Híbrido , VorinostatRESUMO
A novel and efficient algorithm based on a modified Gerchberg-Saxton algorithm (MGSA) in the Fresnel domain is presented, together with mathematical derivation, and two pure phase-only masks (POMs) are generated. The algorithm's application to data hiding is demonstrated by a simulation procedure, in which a hidden image/logo is encoded into phase forms. A hidden image/logo can be extracted by the proposed high-performance lensless optical data-hiding system. The reconstructed image shows good quality and the errors are close to zero. In addition, the robustness of our data-hiding technique is illustrated by simulation results. The position coordinates of the POMs as well as the wavelength are used as secure keys that can ensure sufficient information security and robustness. The main advantages of this proposed watermarking system are that it uses fewer iterative processes to produce the masks, and the image-hiding scheme is straightforward.
RESUMO
PURPOSE: Bath-related thunderclap headache (BRTH) is a rare and usually benign condition. We report a case of episodic explosive thunderclap headache (TH) provoked by showering water, with the complications of cortical subarachnoid hemorrhages (SAH) and delayed intracerebral hemorrhage (ICH). CASE REPORT: A 56-year-old premenopausal woman, without chronic illness or headache history, suffered from 4 episodes of severe explosive TH within 11 days. Two of these attacks were provoked by hot water and 1 by cold water. A small acute SAH was found in the left high frontal cortex on brain computed tomography (CT) performed 7 days after the first attack (day 7). Brain magnetic resonance imaging (MRI) and angiography (MRA) on day 9 disclosed a new acute SAH in the right frontal cortex but with no apparent vasoconstriction. CT angiography (CTA) on day 12 first revealed vasoconstriction in the M2 segment of right middle cerebral artery (MCA), and found a new ICH in the right anterior frontal lobe. Conventional angiography on day 14 revealed partial remission of vasoconstriction with only mild short segmental narrowing at the proximal M1 segment of right MCA. The patient had no clinical neurological deficit. She was free of headache at day 11 when she started taking nimodipine. CONCLUSION: Reversible cerebral vasoconstriction syndrome (RCVS) presented with BRTH is rare and is not always that benign as was once thought. The delayed ICH and the short-period of vasoconstriction in this patient extended our knowledge that the time course of the complications and the duration of vasospasm in RCVS could vary widely among patients. Nimodipine is probably effective in both relieving symptoms and reversing vasoconstriction.
Assuntos
Banhos/efeitos adversos , Hemorragia Cerebral/complicações , Transtornos da Cefaleia Primários/complicações , Hemorragia Subaracnóidea/complicações , Feminino , Transtornos da Cefaleia Primários/tratamento farmacológico , Transtornos da Cefaleia Primários/etiologia , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Nimodipina/uso terapêutico , Vasodilatadores/uso terapêuticoRESUMO
PURPOSE: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasoconstriction and dilatation of intracranial arteries, typically affecting bilateral medium-sized intracranial arteries and their branches. The diagnosis usually relies both on clinical presentations and cerebral vascular imaging such as magnetic resonance angiography or conventional angiography. Dual energy computed tomography angiography (CTA) could provide high-quality imaging and is usually immediately available for the diagnosis at the emergency department. CASE REPORT: A 37-year-old previously healthy woman was admitted to the neurology ward for recurrent episodes of headaches within 3 days. She was diagnosed as having RCVS presenting with thunderclap headaches. Dual energy CTA provided high-quality imaging and almost immediately available for diagnosis at the emergency department (ER). CT perfusion showed adequate brain perfusion. Transcranial Doppler disclosed increased arterial velocities at bilateral middle cerebral arteries. We treated the patient with oral diclofenac and nimodipine. After a few days, she had great improvement of headaches. The follow-up CTA 3 months after her initial presentation disclosed complete resolution of the constrictions of these intracranial arteries. CONCLUSION: Brain magnetic resonance imaging (MRI) with magnetic resonance angiography (MRA) and MR venography is the choice for initial investigation; however, CTA is an alternative diagnostic tool when MRI is not readily available. Dual energy CTA has the great advantage in providing high-resolution imaging, high speed scanning with a lower radiation dose.