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Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). Conclusion: After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.
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Mild cognitive impairment is a typical symptom of early Alzheimer's disease (AD). Glehnia littoralis (G. littoralis), a medicinal halophyte plant commonly used to treat strokes, has been shown to possess some therapeutic qualities. In this study, we investigated the neuroprotective and anti-neuroinflammatory effects of a 50% ethanol extract of G. littoralis (GLE) on lipopolysccharide (LPS)-stimulated BV-2 cells and scopolamine-induced amnesic mice. In the in vitro study, GLE treatment (100, 200, and 400 µg/mL) markedly attenuated the translocation of NF-κB to the nucleus concomitantly with the significant mitigation of the LPS-induced production of inflammatory mediators, including NO, iNOS, COX-2, IL-6, and TNF-α. In addition, the GLE treatment suppressed the phosphorylation of MAPK signaling in the LPS-stimulated BV-2 cells. In the in vivo study, mice were orally administered with the GLE (50, 100, and 200 mg/kg) for 14 days, and cognitive loss was induced via the intraperitoneal injection of scopolamine (1 mg/kg) from 8 to 14 days. We found that GLE treatment ameliorated memory impairment and simultaneously improved memory function in the scopolamine-induced amnesic mice. Correspondingly, GLE treatment significantly decreased the AChE level and upregulated the protein expression of neuroprotective markers, such as BDNF and CREB, as well as Nrf2/HO-1 and decreased the levels of iNOS and COX-2 in the hippocampus and cortex. Furthermore, GLE treatment attenuated the increased phosphorylation of NF-κB/MAPK signaling in the hippocampus and cortex. These results suggest that GLE has a potential neuroprotective activity that may ameliorate learning and memory impairment by regulating AChE activity, promoting CREB/BDNF signaling, and inhibiting NF-κB/MAPK signaling and neuroinflammation.
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Apiaceae , Facteur de transcription NF-kappa B , Souris , Animaux , Facteur de transcription NF-kappa B/métabolisme , Scopolamine/pharmacologie , Facteur neurotrophique dérivé du cerveau/métabolisme , Maladies neuro-inflammatoires , Lipopolysaccharides/effets indésirables , Cyclooxygenase 2/métabolisme , Troubles de la mémoire/induit chimiquement , Troubles de la mémoire/traitement médicamenteux , Troubles de la mémoire/métabolisme , MicroglieRÉSUMÉ
OBJECTIVES: Dilatation of the aortic root structures or ascending aorta is often observed in patients with Fallot-type anomalies. We aimed to determine the dilation rate of the aortic structures and investigate strategies for managing this phenomenon. METHODS: In this retrospective study, we enrolled 66 out of 801 patients who underwent corrective surgery for Fallot-type anomalies (tetralogy of Fallot [TOF] and Fallot-type double outlet right ventricle [DORV]) between 2004 and 2020. These 66 patients had follow-up cardiac computed tomography (CT) angiography images taken at least 5 years after the initial CT study. We analyzed the diameters and aortic cross-sectional area/height ratio (AH) of the aortic annulus, sinus of Valsalva, sinotubular junction, and ascending aorta between the initial and follow-up CT scans. "Dilatation" was defined as a z-score over 2 for each aortic structure. RESULTS: The median age at the initial and follow-up CT scans was 5.9 years (interquartile range [IQR]: 0.4 ~ 12.4) and 15.9 years (IQR 9.3 ~ 23.4), respectively. The median CT interval (from initial to latest CT) was 9.5 years (IQR 6.6 ~ 12.0). The sinus of Valsalva exhibited the most significant dilation (32.8 mm at follow-up CT) over the study period. The AH ratio increased significantly in all four aortic structures. The patient's age was significantly associated with higher AH in the follow-up CT. Aortic dilatation was present in 74.2% of patients at the initial CT and increased to 86.4% at the follow-up CT. CONCLUSION: In Fallot-type anomalies, the AH ratio of aortic root structures significantly increased over an average period of approximately 9.5 years. The number of patients diagnosed with aortic dilatation also increased. Based on our observations in this study, these patients' group should be considered for more frequent follow-up examinations, as significant dilatation could occur in their mid-20 s.
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Maladies de l'aorte , Tétralogie de Fallot , Humains , Nourrisson , Études rétrospectives , Études de suivi , Dilatation , Aorte/imagerie diagnostique , Tétralogie de Fallot/imagerie diagnostique , Tétralogie de Fallot/chirurgie , Tétralogie de Fallot/complications , Maladies de l'aorte/imagerie diagnostique , Dilatation pathologique/complicationsRÉSUMÉ
BACKGROUND: Bone marrow (BM) is progressively filled with adipocytes during aging process. Thus, BM adipocytes-derived adiponectin (APN) affects the function of bone marrow-derived mesenchymal stem cells (BMSCs). However, little is known about the effect of APN on migration ability of BMSCs cultured under hypoxic conditions, which is similar to the BM microenvironment. RESULTS: We found that the population and migration ability of BMSCs from APN KO mice was higher than that of WT mice due to increased stability of hypoxia inducible factor 1α (HIF1α). Stem cell factor (SCF)-activated STAT3 stimulated the induction of HIF1α which further stimulated SCF production, indicating that the SCF/STAT3/HIF1α positive loop was highly activated in the absence of APN. It implies that APN negatively regulated this positive loop by stimulating HIF1α degradation via the inactivation of GSK3ß. Furthermore, APN KO BMSCs were highly migratory toward EL-4 lymphoma, and the interaction between CD44 in BMSCs and hyaluronic acid (HA) from EL-4 enhanced the migration of BMSCs. On the other hand, the migrated BMSCs recruited CD8+ T cells into the EL-4 tumor tissue, resulting in the retardation of tumor growth. Additionally, gradually increased APN in BM on the aging process affects migration and related functions of BMSCs, thus aged APN KO mice showed more significant suppression of EL-4 growth than young APN KO mice due to higher migration and recruitment of CD8+ T cells. CONCLUSION: APN deficiency enhances CD44-mediated migration ability of BMSCs in the hypoxic conditions by the SCF/STAT3/HIF1α positive loop and influences the migration ability of BMSCs for a longer time depending on the aging process. Video Abstract.
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Adiponectine , Cellules souches mésenchymateuses , Animaux , Souris , Moelle osseuse/métabolisme , Cellules de la moelle osseuse , Lymphocytes T CD8+ , Hypoxie/métabolisme , Cellules souches mésenchymateuses/métabolismeRÉSUMÉ
The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of Catalpa ovata extract using an in vitro antioxidant assay. Then, the inhibitory effects of C. ovata extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from C. ovata extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in É-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders.
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Acétates , Bignoniaceae , , Hormone mélanotrope alpha/pharmacologie , Mélanines , Chromatographie en phase liquide , Spectrométrie de masse en tandem , Monophenol monooxygenase , AMP cyclique , ARN messager , Extraits de plantes/pharmacologieRÉSUMÉ
Nanotechnology-applied materials and related therapeutics have gained attention for treating inflammatory skin diseases. The beach rose (Rosa rugosa), belonging to the family Rosaceae, is a perennial, deciduous woody shrub endemic to northeastern Asia. In this study, R. rugosa-based gold nanoparticles (RR-AuNPs) were biologically synthesized under optimal conditions to explore their potential as anti-inflammatory agents for treating skin inflammation. The synthesized RR-AuNPs were analyzed using field emission-transmission electron microscopy, energy-dispersive X-ray spectrometry, selected-area electron diffraction, and X-ray diffraction. The uniformly well-structured AuNPs showed near-spherical and polygonal shapes. Cell viability evaluation and optical observation results showed that the RR-AuNPs were absorbed by human keratinocytes without causing cytotoxic effects. The effects of RR-AuNPs on the skin inflammatory response were investigated in human keratinocytes treated with tumor necrosis factor-α/interferon-γ (T + I). The results showed that T + I-stimulated increases in inflammatory mediators, including chemokines, interleukins, and reactive oxygen species, were significantly suppressed by RR-AuNP treatment in a concentration-dependent manner. The western blotting results indicated that the RR-AuNP-mediated anti-inflammatory effects were highly associated with the suppression of inflammatory signaling, mitogen-activated protein kinase, and nuclear factor-κB. These results demonstrate that plant extract-based AuNPs are novel anti-inflammatory candidates for topical application to treat skin inflammation.
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Chemical accidents have threatened drinking water safety and aquatic systems when hazardous chemicals flow into inland waterbodies through pipelines in industrial complexes. In this study, a forecasting system was developed for the prevention of drinking water resource pollution by considering chemical transport/fate through both pipelines and river channels. To this end, we coupled a pipe network model (Storm Water Management Model) with a calibrated hydrodynamic model (Environmental Fluid Dynamics Code). In addition, we investigated whether chemical transport through pipelines would make a difference in chemical concentration predictions. For both pipelines and river channels, the results showed lower peak concentrations than those without pipelines, whereas the time of peak concentration did not change significantly. When chemicals were transported with both pipelines and river channels, the peak concentrations were 25.81% and 41.91% lower than those of chemicals carried directly into the Han and Geum Rivers without the pipeline transport. Further, our system is automated from scenario generation to analysis and usage is straightforward, with a simple input of accident information. The results of this study can be utilized to establish a safe water supply system and preliminary countermeasures against accidental water pollution in the future.
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Rejet de substances chimiques dangereuses , Eau de boisson , Polluants chimiques de l'eau , Eau de boisson/analyse , Surveillance de l'environnement , Rivières/composition chimique , Polluants chimiques de l'eau/composition chimiqueRÉSUMÉ
A significant growth in demand for online shopping in light of the Coronavirus Disease (COVID) crisis has received attention from transportation practitioners, policy-makers, and researchers. However, an important question arises in this increase in online shopping and resulting deliveries: How long will this last? Very little is known whether this popularity would last a long time. To address this question, the authors conducted a survey of 915 individuals residing in the U.S. and classified them into the four distinctive consumer types (i.e., the prior adopter, temporary adopter and permanent new adopter, and non-adopter) depending on their usage of delivery services before, during, and after (expected) the COVID crisis. This research aims to gain behavioral insight by exploring the differences between the four consumer types and investigating factors affecting the initial adoption and continuance intention of using delivery services. The descriptive analysis revealed that there are clear differences not only between the four types of consumers but also between the four product types (i.e., grocery, food, home goods, and other packages) considered in the survey. The models found that factors affecting the initial adoption and continuance intention are different from the previous studies conducted before the COVID pandemic. Implications for planning and policymaking are also discussed.
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BACKGROUND: This study aimed to compare long-term outcomes, including durability, after bovine pericardial valve replacement with those after porcine mitral valve replacement (MVR). METHODS: We enrolled 309 patients who underwent MV replacement (mean age: 65.8±11.5 years; 68.9% females) with Carpentier-Edwards PERIMOUNT bovine pericardial valves (bovine MVR group, n=241) or Hancock II porcine bioprosthesis (porcine MVR group, n=68). The mean clinical and echocardiographic follow-up durations were 81.4±60.0 and 57.8±53.3 months, respectively. Structural valve deterioration (SVD) was defined as prosthetic mitral valve (MV) regurgitation or stenosis of greater than moderate degree combined with a motion limitation, tear, or perforation of prosthetic valve leaflet on follow-up echocardiography. Propensity score (PS)-adjusted multivariable analyses were performed. RESULTS: Thirty-day mortality rate was 6.4% (20/309 patients). SVD occurred in 50 patients (33 and 17 patients in the bovine and porcine MV replacement groups, respectively). Cumulative incidences of SVD at 5, 10, and 15 years were 3.2%, 15.9%, and 32.4%, respectively, in the bovine MVR group and 1.9%, 15.3%, and 41.7%, respectively, in the porcine MVR group. Cumulative incidences of SVD in the two groups were not different in competing risk analysis (P=0.23). Other clinical outcomes including overall survival and cumulative incidences of cardiac death and MV-related events were not statistically significantly different between the groups in PS-adjusted multivariable analyses. CONCLUSIONS: Long-term clinical outcomes including SVD were not different between the bovine and porcine bioprosthesis MVR groups during average 7 years of clinical follow-up after MVR.
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OBJECTIVES: Clinically, tetralogy of Fallot (TOF) patients who underwent repair late (older than 2 years) appears to have worse outcomes after pulmonary valve replacement than patients who underwent repair early. We proceeded to review the clinical features of late-repaired TOF patients who required pulmonary valve replacement. METHODS: Fifty patients who underwent pulmonary valve replacement after TOF repair over the age of 2 years from 2000 to 2018 were retrospectively reviewed. Pre- and postoperative cardiac magnetic resonance imaging, cardiopulmonary exercise tests, and cardiac catheterization were analysed. RESULTS: The median age of patients at the time of TOF repair and pulmonary valve replacement was 3.6 and 23.4 years, respectively. The median interval from TOF repair to pulmonary valve replacement was 20.5 years. Cardiac magnetic resonance imaging and cardiopulmonary exercise tests were performed at a median of 5.9 and 3.7 years after pulmonary valve replacement, respectively. Cardiac magnetic resonance revealed that there were significant changes in the indexed values of the right ventricle end-diastolic volume (164.7-106.9 ml/m2, P < 0.001), end-systolic volume (101.4-64.9 ml/m2, P < 0.001), stroke volume (66.8-48.0 ml/m2, P = 0.007) and cardiac output (5.1-3.6 l/m2, P = 0.040). Twenty-eight percentage of patients achieved normalization of the right ventricular volume after pulmonary valve replacement. In the exercise test, the maximum rate of oxygen consumption (72.5-69.5%) and oxygen pulse (95.0-83.0%) changed without statistical significance. CONCLUSIONS: Although pulmonary valve replacement after late TOF correction improves right ventricular volume status, only a minority of patients achieve normalization of right ventricular end systolic volume and a normal functional status.
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Insuffisance pulmonaire , Valve du tronc pulmonaire , Tétralogie de Fallot , Adolescent , Adulte , Enfant , Enfant d'âge préscolaire , État fonctionnel , Humains , Valve du tronc pulmonaire/imagerie diagnostique , Valve du tronc pulmonaire/chirurgie , Insuffisance pulmonaire/imagerie diagnostique , Insuffisance pulmonaire/étiologie , Insuffisance pulmonaire/chirurgie , Études rétrospectives , Débit systolique , Tétralogie de Fallot/chirurgie , Résultat thérapeutique , Jeune adulteRÉSUMÉ
BACKGROUND: The COVID-19 pandemic has disrupted all aspects of healthcare, including cardiothoracic surgery (CTS). We sought to determine the pandemic's impact on CTS trainees' educational experiences. METHODS: A survey was developed and distributed to members of the Thoracic Surgery Residents Association and other international CTS trainees. Trainees were asked to evaluate their cumulative experiences and share their overall perceptions of how CTS training had been impacted during the earliest months of the COVID-19 pandemic (i.e., since March 01, 2020). Surveys were distributed and responses were recorded June 25-August 05, 2020. In total, 748 surveys were distributed and 166 responses were received (overall response rate 22.2%). Of these, 126 of 166 responses (75.9%) met inclusion criteria for final analysis. RESULTS: Final responses analyzed included 45 of 126 (35.7%) United States (US) and 81 of 126 (64.3%) international trainees, including 101 of 126 (80.2%) senior and 25 of 126 (19.8%) junior trainees. Most respondents (76/126, 43.2%) lost over 1 week in the hospital due to the pandemic. Juniors (12/25, 48.0%) were more likely than seniors (20/101, 19.8%) to be reassigned to COVID-19-specific units (p < .01). Half of trainees (63/126) reported their case volumes were reduced by over 50%. US trainees (42/45, 93.3%) were more likely than international trainees (58/81, 71.6%) to report reduced operative case volumes (p < .01). Most trainees (104/126, 83%) believed their overall clinical acumen was not adversely impacted by the pandemic. CONCLUSIONS: CTS trainees in the United States and abroad have been significantly impacted by the COVID-19 pandemic, with time lost in the hospital, decreased operative experiences, less time on CTS services, and frequent reassignment to COVID-19-specific care settings.
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COVID-19 , Internat et résidence , Spécialités chirurgicales , Humains , Pandémies , SARS-CoV-2 , Enquêtes et questionnaires , États-Unis , EffectifRÉSUMÉ
BACKGROUND: The double-lumen cannula (DLC) has begun to be used worldwide for venovenous (VV) extracorporeal membrane oxygenation (ECMO). We aimed to examine whether the DLC could be an effective tool in the treatment of pediatric respiratory failure in Korea. METHODS: We reviewed the records of patients weighing under 15 kg who underwent ECMO due to respiratory failure between January 2017 and December 2018. Outcomes of ECMO using a DLC and conventional ECMO using central method or 2 peripheral cannulas were compared. RESULTS: Twelve patients were treated with ECMO for respiratory failure. Among them, a DLC was used in 5 patients, the median age of whom was 3.8 months (interquartile range, 0.1-49.7 months). In these patients, the median values of pH, partial pressure of carbon dioxide, and partial pressure of oxygen were 7.09, 74 mm Hg, and 37 mm Hg before ECMO and corrected to 7.31, 44 mm Hg, and 85 mm Hg, respectively, after ECMO cannulation. Median blood flow rate in the patients treated with ECMO using a DLC was slightly higher than that in the conventional ECMO group, but this difference was not statistically significant (86.1 mL/kg/min and 74.3 mL/kg/min, respectively; p=1.00). One patient from the DLC group and 3 patients from the conventional group were weaned off ECMO. CONCLUSION: VV ECMO using a DLC provided adequate oxygenation, ventilation, and blood flow rate in Korean pediatric patients with respiratory failure. Further prospective and randomized studies are warranted.
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Insertion of an epicardial pacemaker is a useful treatment for pediatric patients with an abnormal heart rhythm. However, there are limitations and concerns when implanting epicardial pacemakers in infants and neonates due to their small body size. We report a patient who experienced rare complications after implantation of a permanent pacemaker.
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We investigated the prognosis of patients with dry pleural dissemination (DPD) of non-small cell lung cancer (NSCLC) and the risk factors of developing to malignant pleural effusion (MPE).We retrospectively reviewed 104 patients with NSCLC and DPD, confirmed surgically from 1996 to 2016. Incidence rate and risk factors of MPE were analyzed statistically. The prognosis of NSCLC patients with MPE was evaluated using the Kaplan-Meier method.The most common histologic type was adenocarcinoma in 95 (91.3%) patients. The median follow-up duration was 65.5 months and the median survival time was 37.7 months. MPE developed in 51 (49%) patients, and the median effusion-free interval was 41.9 months. The median survival time of the patients with and without MPE was not different (41.3 vs 31.7 months, Pâ=â.16). No predictive factors for the development of MPE were identified. Fifteen (14.4%) patients underwent invasive procedures for the management of MPE.Almost half of all patients with NSCLC and DPD experienced MPE, and 14.4% patients developed symptomatic MPE requiring invasive procedures. MPE in DPD did not affect the survival in NSCLC patients.
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Carcinome pulmonaire non à petites cellules/épidémiologie , Tumeurs du poumon/épidémiologie , Épanchement pleural malin/épidémiologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Carcinome pulmonaire non à petites cellules/étiologie , Carcinome pulmonaire non à petites cellules/mortalité , Femelle , Humains , Tumeurs du poumon/étiologie , Tumeurs du poumon/mortalité , Mâle , Adulte d'âge moyen , Métastase tumorale , Épanchement pleural malin/étiologie , Épanchement pleural malin/mortalité , Pronostic , République de Corée/épidémiologie , Études rétrospectives , Facteurs de risque , Analyse de survieRÉSUMÉ
The estimated mortality rates for breast and cervical cancer in Cambodia are high, perhaps because the Cambodian population lacks information about their detection and prevention. This cross-sectional study assessed the distribution of cervical cancers among and the behavioural and clinical characteristics of Cambodian women. It comprised 1039 Cambodian women who were interviewed between August 2013 and January 2016; the interviews were conducted in person using structured questionnaires. Among the participants, 801 (77.2%) and 709 (68.3%) had heard of cervical cancer and cervical cancer detection tests, respectively. However, 830 (80.2%) had never undergone a Pap smear, and 633 (60.9%) had never heard of breast self-examination. Despite the high mortality rates for breast and cervical cancer in Cambodia, only a small percentage of the participants had risk factors (e.g. smoking, alcohol consumption) for female cancers. A nationwide survey of the knowledge, attitudes and practices related to female cancers is recommended.Impact StatementWhat is already known on this subject? The estimated incidence and mortality rates of breast and cervical cancers in Cambodia are high. How much Cambodian women know about these cancers and whether they are receptive to cancer screening are questions requiring further study.What do the results of this study add? To our knowledge, this is the first study to describe the female cancer-related behavioural and clinical characteristics of Cambodian women. We show that rural Cambodian women are mostly unaware of breast and cervical cancer screening and that only a small percentage had risk factors for these cancers, despite the high incidence of these cancers in Cambodia.What are the implications of these findings for clinical practice and/or further research? Our findings potentially aid the design of programmes that increase awareness of breast and cervical cancers in Cambodia. Such programmes would be expected to reduce the incidence and mortality rates of these cancers in this country. Nationwide screening programmes for female cancers should be implemented in Cambodia.
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Tumeurs du sein/diagnostic , Dépistage précoce du cancer/psychologie , Connaissances, attitudes et pratiques en santé , Tumeurs du col de l'utérus/diagnostic , Adulte , Tumeurs du sein/mortalité , Tumeurs du sein/psychologie , Cambodge/épidémiologie , Études transversales , Dépistage précoce du cancer/méthodes , Dépistage précoce du cancer/statistiques et données numériques , Femelle , Comportement en matière de santé , Humains , Adulte d'âge moyen , Appréciation des risques , Facteurs de risque , Population rurale/statistiques et données numériques , Enquêtes et questionnaires , Population urbaine/statistiques et données numériques , Tumeurs du col de l'utérus/mortalité , Tumeurs du col de l'utérus/psychologieRÉSUMÉ
Veno-venous extracorporeal membrane oxygenation (ECMO) is a useful mechanical device for pediatric patients with severe respiratory failure. Conventional veno-venous ECMO using double cannulation, however, is not feasible due to size limitations in pediatric patients who have small femoral vessels. Recently, percutaneous bicaval dual-lumen cannula can be inserted using single cannulation via the right internal jugular vein. Herein, we report the case of a pediatric patient with severe respiratory failure who was weaned off the ECMO successfully after treatment with bicaval dual-lumen cannulation for 5 days despite the small body size and immunocompromised condition due to chemotherapy for hemophagocytic lymphohistiocytosis.
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Large DNA molecules are a promising platform for in vitro single-molecule biochemical analysis to investigate DNA-protein interactions by fluorescence microscopy. For many studies, intercalating fluorescent dyes have been primary DNA staining reagents, but they often cause photo-induced DNA breakage as well as structural deformation. As a solution, we previously developed several fluorescent-protein DNA-binding peptides or proteins (FP-DBP) for reversibly staining DNA molecules without structural deformation or photo-induced damage. However, they cannot stain DNA in a condition similar to a physiological salt concentration that most biochemical reactions require. Given these concerns, here we developed a salt-tolerant FP-DBP: truncated transcription activator-like effector (tTALE-FP), which can stain DNA up to 100 mM NaCl. Moreover, we found an interesting phenomenon that the tTALE-FP stained DNA evenly in 1 × TE buffer but showed AT-rich specific patterns from 40 mM to 100 mM NaCl. Using an assay based on fluorescence resonance energy transfer, we demonstrated that this binding pattern is caused by a higher DNA binding affinity of tTALE-FP for AT-rich compared to GC-rich regions. Finally, we used tTALE-FP in a single molecule fluorescence assay to monitor real-time restriction enzyme digestion of single DNA molecules. Altogether, our results demonstrate that this protein can provide a useful alternative as a DNA stain over intercalators.
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Protéines de liaison à l'ADN/métabolisme , ADN/composition chimique , ADN/métabolisme , Colorants fluorescents/composition chimique , Intercalants/métabolisme , Coloration et marquage/méthodes , Effecteurs de type activateur de transcription/métabolisme , Protéines de liaison à l'ADN/composition chimique , Fluorescence , Transfert d'énergie par résonance de fluorescence , Humains , Intercalants/composition chimique , Microscopie de fluorescence , Imagerie de molécules uniques/méthodes , Effecteurs de type activateur de transcription/composition chimiqueRÉSUMÉ
BACKGROUND AND AIMS: Recent studies have shown that etomidate is associated with fewer serious adverse events than propofol and has a noninferior sedative effect. We investigated whether etomidate-midazolam is associated with fewer cardiopulmonary adverse events and has noninferior efficacy compared to propofol-midazolam for screening colonoscopy in the elderly. METHODS: A prospective, single-center, double-blinded, randomized controlled trial was performed. Patients aged over 65 years who were scheduled to undergo screening colonoscopy were randomized to receive either etomidate or propofol based on midazolam. The primary outcome was all cardiopulmonary adverse events. The secondary outcomes were vital sign fluctuation (VSF), adverse events disturbing the procedure, and sedation-related outcomes. RESULTS: The incidence of cardiopulmonary adverse events was higher in the propofol group (72.6%) than in the etomidate group (54.8%) (Pâ=â.040). VSF was detected in 17 (27.4%) and 31 (50.0%) patients in the etomidate and propofol groups, respectively (Pâ=â.010). The incidence rate of adverse events disturbing the procedure was significantly higher in the etomidate group (25.8%) than in the propofol group (8.1%) (Pâ=â.008). Moreover, the incidence rate of myoclonus was significantly higher in the etomidate group (16.1%) than in the propofol group (1.6%) (Pâ=â.004). There was no statistical significance between the 2 groups with respect to sedation times and sedation-related outcomes including patients' and endoscopist's satisfaction. In the multivariate analysis, the etomidate group had significantly low odds ratio (OR) associated with VSF (OR: 0.407, confidence interval: 0.179-0.926, Pâ=â.032). CONCLUSIONS: We recommend using etomidate-midazolam in patients with high ASA score or vulnerable to risk factors; propofol-midazolam may be used as a guideline in patients with low ASA score.
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Anesthésiques intraveineux/effets indésirables , Coloscopie/méthodes , Étomidate/effets indésirables , Midazolam/effets indésirables , Propofol/effets indésirables , Sujet âgé , Anesthésiques intraveineux/usage thérapeutique , Maladies cardiovasculaires/induit chimiquement , Maladies cardiovasculaires/épidémiologie , Méthode en double aveugle , Étomidate/usage thérapeutique , Femelle , Humains , Maladies pulmonaires/épidémiologie , Maladies pulmonaires/étiologie , Mâle , Dépistage de masse/méthodes , Midazolam/usage thérapeutique , Adulte d'âge moyen , Myoclonie/induit chimiquement , Propofol/usage thérapeutique , Études prospectives , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVES: Bowel cleansing is a major patient complaint during colonoscopy. Adding laxatives to the bowel preparation is effective in replacing a portion of bowel preparation solution and reducing its volume. Prucalopride is a serotonin receptor agonist that stimulates gastrointestinal motility and provides propulsive force for defecation. This study aimed to compare 1 L polyethylene glycol (PEG) with ascorbic acid (Asc) plus 2 mg prucalopride (1LP/AP) and 2 L PEG with Asc (2LP/A) for colonoscopy preparation with respect to bowel-cleansing quality and side effects. METHODS: A single-center, randomized, prospective study was conducted with 260 outpatients administered either 1LP/AP or 2LP/A. The primary endpoint was bowel preparation quality, which was evaluated using the Boston Bowel Preparation Scale and Aronchick Bowel Preparation Scale, and the secondary endpoints were patient tolerability and acceptability, assessed by a questionnaire-based survey. RESULTS: The adequate bowel preparation rates were 88.5% and 83.1% in the 2LP/A and 1LP/AP groups, respectively, and the efficacy of 1LP/AP was equivalent to the control regimen (p=.216). Other colonoscopic variables including adenoma detection rate were similar in both groups. Patient tolerability and acceptability were not significantly different, but patients in the 1LP/AP group were more willing to repeat the same regimen (p=.039). CONCLUSIONS: Bowel preparation quality with 1LP/AP was equivalent to that with 2LP/A, which did not increase the occurrence of side effects, but it reduced the volume of the solution ingested, and increased patient satisfaction.