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The emergence of rice black-streaked dwarf virus (RBSDV) poses a significant threat to global cereal crop cultivation, necessitating the urgent development of reliable detection and quantification techniques. This study introduces a reliable approach for the precise and sensitive quantification of the RBSDV in cereal crop samples, employing a reverse transcription digital polymerase chain reaction (RT-dPCR) assay. We assessed the specificity and sensitivity of the RT-dPCR assay proposed for precise RBSDV detection and quantification. Our findings demonstrate that RT-dPCR was specific for detection of RBSDV, with no cross-reactivity observed with other viruses infecting cereal crops. The RT-dPCR sensitivity was over 10 times that of RT-quantitative PCR (RT-qPCR). The detection limit of RT-dPCR was 0.096 copies/µl. In addition, evaluation of RT-dPCR assay with field samples was conducted on 60 different cereal crop samples revealed that RT-dPCR (45/60) exhibited superior accuracy compared with RT-qPCR (23/60). In this study, we present a specific and accurate RT-dPCR assay for the detection and quantification of RBSDV.
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STUDY OBJECTIVE: Asystole is the most common initial rhythm in out-of-hospital cardiac arrest (OHCA) but indicates a low likelihood of neurologic recovery. This study aimed to develop a novel scoring system to be easily applied at the time of emergency department arrival for identifying favorable neurologic outcomes in OHCA survivors with an asystole rhythm. METHODS: This study is a secondary analysis based on a previously collected nationwide database, targeting nontraumatic adult OHCA patients aged ≥18 years with an asystole rhythm who achieved return of spontaneous circulation (ROSC) between January 2016 and December 2020. The primary outcome was a favorable neurologic outcome defined as Cerebral Performance Categories scores of 1 or 2 at hospital discharge. A prediction model was developed through multivariable logistic regression analysis in a derivation cohort in the form of a scoring system (WBC-ASystole). The performance and calibration of the model were tested using an internal validation cohort. RESULTS: Among 19,803 OHCA patients with survival to hospital admission, 6,322 had asystole, and 285 (4.5%) achieved good neurologic outcomes. Factors associated with favorable outcomes included age, witness arrest, bystander cardiopulmonary resuscitation, time from call to hospital arrival, and out-of-hospital ROSC achievement. The WBC-ASystole score, totaling 11 points, exhibited a predictive performance with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [CI] 0.76 to 0.83) and 0.79 (95% CI 0.74 to 0.83) in the derivation and validation cohorts, respectively. After categorizing patients into 3 groups based on probability for good neurologic outcomes, the sensitivity and specificity were as follows: 0.98 (95% CI 0.97 to 0.99) and 0.09 (95% CI 0.09 to 0.10) for the very low predicted probability group (WBC-ASystole ≤2), 0.85 (95% CI 0.82 to 0.89) and 0.54 (95% CI 0.53 to 0.55) for the low predicted probability group (WBC-ASystole 3 to 4), and 0.36 (95% CI 0.34 to 0.39) and 0.93 (95% CI 0.92 to 0.93) for fair predicted probability group (WBC-ASystole≥5), respectively. CONCLUSIONS: Although external validation studies must be performed, among OHCA patients with asystole, the WBC-ASystole scoring system may identify those patients who are likely to have a favorable neurologic outcome.
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BACKGROUND: Cardiopulmonary resuscitation (CPR) is the cornerstone intervention for cardiac arrest, with extracorporeal CPR (ECPR) demonstrating enhanced survival and neurologic outcomes in in-hospital cardiac arrest. This study explores the time interval between CPR initiation and the onset of extracorporeal membrane oxygenation (ECMO) in ECPR recipients, investigating its impact on survival outcomes. METHODS: This retrospective analysis included 1950 adults who received CPR at a single medical center between March 2019 and April 2023. Data from 198 adult patients who had ECMO inserted during CPR were analyzed. The interval from CPR initiation to ECMO initiation was quantified and categorized as ≤20, 20-40, and >40 min. Cox regression analysis assessed associations between CPR-to-ECMO time and short- and long-term mortalities. RESULTS: Among the 198 patients who underwent ECPR, 116 (58.6%) experienced 30-day mortality. Initiation of ECMO within 20 min occurred in 46 (23.2%), whereas 74 (37.4%) had ECMO initiated after 40 min. Cox regression revealed a significant association between time from CPR to ECMO initiation and 30-day mortality (adjusted hazard ratio [HR]: 2.20 in >40 min, HR: 2.63 in 20-40 min, p = 0.006) and 6-month mortality (HR: 1.81, in >40 min, HR: 1.99 in 20-40 min, p = 0.021). CONCLUSIONS: This study revealed that, in ECPR recipients, a shorter duration between CPR initiation and ECMO flow commencement is associated with improved short- and long-term patient prognoses. These findings emphasize the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR.
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Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSµC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSµC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 µm) toward the inner wall, while directing smaller ones (avg. diameter: 23 µm) outward. Utilizing ITSµC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSµC suggests its potential in differentiating a wide range of heterogeneous cell populations.
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Separação Celular , Humanos , Separação Celular/métodos , Separação Celular/instrumentação , Linhagem Celular Tumoral , Poliestirenos/química , Dispositivos Lab-On-A-Chip , Tamanho da Partícula , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Células Gigantes/citologia , Células Gigantes/patologia , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aß) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3ß and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration.
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Doença de Alzheimer , Encéfalo , Privação do Sono , Animais , Camundongos , Privação do Sono/metabolismo , Privação do Sono/complicações , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas tau/metabolismo , Acetilglucosamina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Sono REM/fisiologia , Peptídeos beta-Amiloides/metabolismoRESUMO
Glutathione (GSH) is indispensable for maintaining redox homeostasis in biological fluids and serves as a key component in cellular defense mechanisms. Accurate assessment of GSH relative to its oxidized counterpart, glutathione disulfide (GSSG), is critical for the early diagnosis and understanding of conditions related to oxidative stress. Despite existing methods for their quantification, the label-free and simultaneous measurement of GSH and GSSG in biological fluid presents significant challenges. Herein, we report the use of an alpha-hederin (Ah) nanopore for the direct measurement of the GSH:GSSG ratio in simulated biological fluid, containing fetal bovine serum (FBS). This system hinges on detecting characteristic relative ion blockades (ΔI/Io) as GSH and GSSG molecules pass through the Ah nanopore under an applied electric field. The distinct current blockage signals derived from the translocation of GSH and GSSG enabled us to determine the molar ratio of GSH and its oxidized form. Notably, the interactions between the hydroxyl groups of the sugar moiety lining the nanopore's inner surface and the sulfhydryl group of GSH significantly influence the translocation dynamics, resulting in a longer translocation time for GSH compared to GSSG. The Ah nanopore technology proposed in this study offers a promising approach for real-time, single molecule-level monitoring of glutathione redox status in biological fluids, eliminating the need for labeling or extensive sample preparation.
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Técnicas Biossensoriais , Dissulfeto de Glutationa , Glutationa , Nanoporos , Oxirredução , Glutationa/química , Glutationa/análise , Glutationa/sangue , Técnicas Biossensoriais/métodos , Dissulfeto de Glutationa/análise , Dissulfeto de Glutationa/química , Dissulfeto de Glutationa/sangue , Animais , Humanos , Bovinos , Estresse OxidativoRESUMO
The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).
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Hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-BC) is the most common type with a favorable prognosis under endocrine therapy. However, it still demonstrates unpredictable progression and recurrences influenced by high tumoral diversity and microenvironmental status. To address these heterogeneous molecular characteristics of HR+/HER2-BC, we aimed to simultaneously characterize its transcriptomic landscape and genetic architecture at the same resolution. Using advanced single-cell RNA and DNA sequencing techniques together, we defined four distinct tumor subtypes. Notably, the migratory tumor subtype was closely linked to genomic alterations of EGFR, related to the tumor-promoting behavior of IL6-positive inflammatory tumor-associated fibroblast, and contributing to poor prognosis. Our study comprehensively utilizes integrated analysis to uncover the complex dynamics of this breast cancer subtype, highlighting the pivotal role of the migratory tumor subtype in influencing surrounding cells. This sheds light on potential therapeutic targets by offering enhanced insights for HR+/HER2-BC treatment.
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Neoplasias da Mama , Fibroblastos Associados a Câncer , Movimento Celular , Receptor ErbB-2 , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Regulação Neoplásica da Expressão Gênica , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Microambiente Tumoral , Linhagem Celular Tumoral , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Prognóstico , Receptores ErbB/metabolismo , Receptores ErbB/genética , Análise de Célula ÚnicaRESUMO
Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.
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Coma , Parada Cardíaca Extra-Hospitalar , Fosfopiruvato Hidratase , Humanos , Fosfopiruvato Hidratase/sangue , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Coma/etiologia , Idoso , Sobreviventes , Prognóstico , Hipotermia Induzida , AdultoRESUMO
Traditional monoclonal antibodies such as Trastuzumab encounter limitations when treating Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer, particularly in cases that develop resistance. This study introduces plant-derived anti-HER2 variable fragments of camelid heavy chain domain (VHH) fragment crystallizable region (Fc) KEDL(K) antibody as a potent alternative for overcoming these limitations. A variety of biophysical techniques, in vitro assays, and in vivo experiments uncover the antibody's nanoscale binding dynamics with transmembrane HER2 on living cells. Single-molecule force spectroscopy reveals the rapid formation of two robust bonds, exhibiting approximately 50 pN force resistance and bond lifetimes in the second range. The antibody demonstrates a specific affinity for HER2-positive breast cancer cells, including those that are Trastuzumab-resistant. Moreover, in immune-deficient mice, the plant-derived anti-HER2 VHH-FcK antibody exhibits superior antitumor activity, especially against tumors that are resistant to Trastuzumab. These findings underscore the plant-derived antibody's potential as an impactful immunotherapeutic strategy for treating Trastuzumab-resistant HER2-positive breast cancer.
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Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2 , Trastuzumab , Trastuzumab/química , Trastuzumab/farmacologia , Humanos , Receptor ErbB-2/imunologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/imunologia , Animais , Feminino , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/química , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: The average glycated hemoglobin (HbA1c) may not accurately reflect glycemic control status during the mid-term after acute myocardial infarction (AMI). We aimed to evaluate changes in HbA1c and their effect on mid-term clinical outcomes in patients with diabetes and AMI. METHODS: We enrolled patients with diabetes ( n â =â 967) who underwent HbA1c measurement in the Korean nationwide registry. These patients were categorized into three groups based on changes in HbA1c from index admission to the 1-year follow-up visit: a decrease in HbA1câ >â 1%, changes in HbA1c within 1%, and an increase in HbA1câ >â 1%. Clinical outcomes at 24 months were examined. RESULTS: The baseline HbA1c levels were 8.55â ±â 0.85, 7.00â ±â 0.98 and 7.07â ±â 1.05 ( P â =â 0.001) and HbA1c levels after 1 year were 6.62â ±â 0.73, 7.05â ±â 0.98 and 9.26â ±â 1.59 ( P â =â 0.001) for patients with 3 groups, respectively. Patients with a 1% decrease in HbA1c had significantly lower incidence of major adverse cardiovascular events (MACE), cardiac death, and rehospitalization after 24 months than those with a 1% increase in HbA1c. However, in the Cox regression analysis, a >1% decrease in HbA1c change was not an independent factor for MACE, cardiac death, and rehospitalization. CONCLUSIONS: Our analysis indicates that an HbA1c decrease of >1% within the first 12 months was not an independent prognostic factor until the 24-month mark. Therefore, standard diabetic control is recommended for patients with diabetes and AMI for up to 2 years.
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Biomarcadores , Diabetes Mellitus , Hemoglobinas Glicadas , Infarto do Miocárdio , Sistema de Registros , Humanos , Hemoglobinas Glicadas/metabolismo , Masculino , Feminino , Infarto do Miocárdio/sangue , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Idoso , Fatores de Tempo , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Biomarcadores/sangue , Fatores de Risco , Readmissão do Paciente/estatística & dados numéricos , Glicemia/metabolismo , Controle Glicêmico/métodos , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). METHODS: This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. RESULTS: Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983-0.991; p < 0.001, OR 7.277; 95% CI 1.856-28.535; p = 0.004, and OR 1.261; 95% CI 1.021-1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832-0.904; p < 0.001), 0.821 (95% CI 0.778-0.859; p < 0.001), and 0.784 (95% CI 0.738-0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. CONCLUSION: The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH.
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This study aimed to elucidate the role of O-GlcNAc cycling in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD)-like neurodegeneration and the underlying mechanisms. We observed dose-dependent downregulation of O-GlcNAcylation, accompanied by an increase in O-GlcNAcase following 6-OHDA treatment in both mouse brain and Neuro2a cells. Interestingly, elevating O-GlcNAcylation through glucosamine (GlcN) injection provided protection against PD pathogenesis induced by 6-OHDA. At the behavioral level, GlcN mitigated motor deficits induced by 6-OHDA, as determined using the pole, cylinder, and apomorphine rotation tests. Furthermore, GlcN attenuated 6-OHDA-induced neuroinflammation and mitochondrial dysfunction. Notably, augmented O-GlcNAcylation, achieved through O-GlcNAc transferase (OGT) overexpression in mouse brain, conferred protection against 6-OHDA-induced PD pathology, encompassing neuronal cell death, motor deficits, neuroinflammation, and mitochondrial dysfunction. These collective findings suggest that O-GlcNAcylation plays a crucial role in the normal functioning of dopamine neurons. Moreover, enhancing O-GlcNAcylation through genetic and pharmacological means could effectively ameliorate neurodegeneration and motor impairment in an animal model of PD. These results propose a potential strategy for safeguarding against the deterioration of dopamine neurons implicated in PD pathogenesis.
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Camundongos Endogâmicos C57BL , N-Acetilglucosaminiltransferases , Oxidopamina , Doença de Parkinson , Animais , Oxidopamina/farmacologia , Camundongos , N-Acetilglucosaminiltransferases/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Masculino , Glucosamina/farmacologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Acetilglucosamina/metabolismo , Acetilglucosamina/farmacologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , beta-N-Acetil-Hexosaminidases/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.
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Hemorragia Pós-Parto , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Hemorragia Pós-Parto/terapia , Transfusão de Sangue , Serviço Hospitalar de Emergência , Frequência CardíacaRESUMO
Chemoresistance is a major cause of treatment failure in many cancers. However, the life cycle of cancer cells as they respond to and survive environmental and therapeutic stress is understudied. In this study, we utilized a microfluidic device to induce the development of doxorubicin-resistant (DOXR) cells from triple negative breast cancer (TNBC) cells within 11 days by generating gradients of DOX and medium. In vivo chemoresistant xenograft models, an unbiased genome-wide transcriptome analysis, and a patient data/tissue analysis all showed that chemoresistance arose from failed epigenetic control of the nuclear protein-1 (NUPR1)/histone deacetylase 11 (HDAC11) axis, and high NUPR1 expression correlated with poor clinical outcomes. These results suggest that the chip can rapidly induce resistant cells that increase tumor heterogeneity and chemoresistance, highlighting the need for further studies on the epigenetic control of the NUPR1/HDAC11 axis in TNBC.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Resistencia a Medicamentos Antineoplásicos , Doxorrubicina/farmacologia , Proteínas Nucleares/metabolismo , Dispositivos Lab-On-A-Chip , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy. Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed. Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life. Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer.
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OBJECTIVES: The timing of preoperative imaging in patients with lung cancer is a debated topic, as there are limited data on cancer progression during the interval between clinical staging by imaging and pathological staging after resection. We quantified disease progression during this interval in patients with early stage non-small-cell lung cancer (NSCLC) to better understand if its length impacts upstaging. METHODS: We retrospectively reviewed our institutional database to identify patients who underwent surgery for clinically staged T1N0M0 NSCLC from January 2015 through September 2022. Tumour upstaging between chest computed tomography (CT) and surgery were analysed as a function of time (<30, 30-59, ≥60 days) for different nodule subtypes. We analysed data across 3 timeframes using Pearson's chi-squared and analysis of variance tests. RESULTS: During the study period, 622 patients underwent surgery for clinically staged T1N0M0 NSCLC. CT-to-surgery interval was <30 days in 228 (36.7%), 30-59 days in 242 (38.9%) and ≥60 days in 152 (24.4%) with no differences in patient or nodule characteristics observed between these groups. T-stage increased in 346 patients (55.6%) between CT imaging and surgery. Among these patients, 126 (36.4%) had ground-glass nodules, 147 (42.5%) had part-solid nodules and 73 (21.1%) had solid nodules. CT-to-surgery interval length was not associated with upstaging of any nodule subtype (full-cohort, P = 0.903; ground-glass, P = 0.880; part-solid, P = 0.858; solid, P = 0.959). CONCLUSIONS: This single-centre experience suggests no significant association between tumour upstaging and time from imaging to lung resection in patients with clinical stage IA NSCLC. Further studies are needed to better understand the risk factors for upstaging.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Fatores de Risco , Estadiamento de NeoplasiasRESUMO
Peanut (Arachis hypogaea L.) has long been cultivated worldwide as an important crop for oil and protein production. Among the various diseases in peanut plants, wilt diseases caused by soil-borne pathogens such as Ralstonia solanacearum and Verticillium dahliae are especially destructive and substantially diminish both quantity and quality in peanut production (Kokalis-Burelle et al., 1997; Thiessen et al., 2012). In July 2022, wilt symptoms were observed in 1 to 3% of the area of peanut fields in Yeoju-si, Korea (37°23´04.0ËN; 127°33´43.0ËE). The xylem in the stems of the wilted plants was dark brown at the soil-surface, which is a representative symptom of vascular wilt pathogens (Yadeta et al. 2013). To isolate the causative pathogens, the stems exhibiting dark lesions were disinfected with 1% NaOCl for 1 min, rinsed with sterile distilled water, and placed on potato dextrose agar medium. The plates were incubated at 25â for 2 days, and white hyphae that grew out from the tissues were subcultured twice on V8 juice agar (V8A) medium. Among the 3 isolates, morphological characteristics of the representative strain YJ1-2 were observed under a microscope. The sporangia were terminal intercalary, filamentous, inflated lobulate, and ranging from 37.4 to 73.6 µm in diameter. The antheridia were diclinous, with clavate, elongate, and crook-necked shapes. The oogonia were mostly globose, with an average of 27.1 µm (range from 20.2 to 35.2 µm, n = 50) in diameter, and mated with one to several antheridia. Both plerotic or aplerotic oospores were observed. Overall, the morphological characteristics of the sporangia, antheridia, oogonia, and oospores indicated that YJ1-2 belongs to the genus Pythium. To genetically characterize YJ1-2, genomic DNA was extracted using cetyltrimethylammonium bromide buffer, and the internal transcribed spacer (ITS) region and cytochrome c oxidase subunit I (cox1) gene were amplified by PCR using primer sets ITS4/ITS5 and OomCoxI-Levlo/ OomCoxI-Levup, respectively (White et al., 1990; Robideau et al. 2011), sequenced, and identified using BLASTN (NCBI, National Center for Biotechnology Information). The ITS sequence (NCBI Acc. No. OR125595) of YJ1-2 has 99% similarity with that of P. myriotylum isolate PY39 (NCBI Acc. No. KX671096). A neighbor-joining phylogenetic tree was constructed from aligned cox1 sequence (NCBI Acc. No. OR224334) of the 10 Pythium species strains including YJ1-2 by CLUSTALW method was used as an outgroup. The YJ1-2 was most closely related to P. myriotylum isolate PM30 (NCBI Acc. No. MT823167). To substantiate the pathogenicity of YJ1-2, the crown roots of peanut plants grown in pots for 4 weeks were wounded using a sterile tweezer, and the mycelial plugs of YJ1-2 cultured for 5 days on V8A were inoculated on the wounds. The inoculated plants were cultivated in a growth chamber at 30â and 70% relative humidity with a 12-h photoperiod. The infected peanut plants exhibited wilt symptoms 11 days after inoculation, consistent with the initial observation, while uninoculated plants remained healthy. To satisfy Koch's postulates, white mycelia were re-isolated from the stems of inoculated plants and axenically cultured in V8A. The morphologies and ITS sequences of the re-isolates were consistent with those of YJ1-2. P. myriotylum has been reported as a causal pathogen of peanut pod rot in the United States and China. However, to the best of our knowledge, this is the first report of wilt disease in peanut plants caused by P. myriotylum in Korea. To prevent the incidence of wilt disease, we will continue our investigations to develop control strategies, including the selection of appropriate agrochemicals.
RESUMO
With the analysis of nationwide health claim data, treatment with the composite agent of SERMs and vitamin D reduces the risk of osteoporotic fracture and hip fracture better compared to SERMs treatment in women with osteoporosis aged ≥ 50 years. PURPOSE: This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50 years. METHODS: The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017-2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan-Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups. RESULTS: The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09-0.71; p = 0.009). No difference was observed between the groups regarding mortality. CONCLUSION: The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk.