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BACKGROUND: Venous air embolism (VAE) is a potentially lethal condition, with a reported incidence rate of about 0.13%, and the true incidence may be higher since many VAE are asymptomatic. The current treatments for VAE include Durant's maneuver, aspiration and removal of air through venous catheters, and hyperbaric oxygen therapy. For critically ill patients, use of cardiotonic drugs and chest compressions remain useful strategies. The wider availability of extracorporeal membrane oxygenation (ECMO) has brought a new option for VAE patients. CASE SUMMARY: A 53-year-old female patient with VAE presented to the emergency clinic due to abdominal pain with fever for 1 d and unconsciousness for 2 h. One day ago, the patient suffered from abdominal pain, fever, and diarrhea. She suddenly became unconscious after going to the toilet during the intravenous infusion of ciprofloxacin 2 h ago, accompanied by nausea and vomiting, during which a small amount of gastric contents were discharged. She was immediately sent to a local hospital, where cranial and chest computed tomography showed bilateral pneumonia as well as accumulated air visible in the right ventricle and pulmonary artery. The condition deteriorated despite endotracheal intubation, rehydration, and other treatments, and the patient was then transferred to our hospital. Veno-arterial ECMO was applied in our hospital, and the patient's condition gradually improved. The patient was successfully weaned from ECMO and extubated after two days. CONCLUSION: ECMO may be an important treatment for patients with VAE in critical condition.
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BACKGROUND: The relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA. METHODS: Data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA. RESULTS: A total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 [95%CI, 1.02-1.26]) after fully adjusting for potential confounders. CONCLUSIONS: Compared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk.
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Ejercicio Físico , Hiperuricemia , Encuestas Nutricionales , Ácido Úrico , Humanos , Hiperuricemia/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estados Unidos/epidemiología , Ácido Úrico/sangre , AncianoRESUMEN
Background: Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results. Objective: To evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults. Methods: A cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011-2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders. Results: The study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05-2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20-4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34-4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03-3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18-4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31-4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24-3.66), third (OR = 2.40, 95% CI = 1.28-4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08-4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors. Conclusion: Higher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.
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BACKGROUND: As pregnant women are excluded from clinical trials of inactivated SARS-CoV-2 vaccines, it is important to assess the immune response in women receiving the vaccination while unknowingly pregnant. METHODS: In a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18-45 years. Serum antibody levels induced by inactivated vaccines were determined. Adverse events were collected by self-reported survey after vaccination. Logistic regression model and restricted cubic spline model were used to investigate the association of factors with antibody positivity. RESULTS: As the doses of the vaccine increase, neutralizing antibody (NAb) positivity was 98.3%, 39.5%, and 9.5% in pregnant women, respectively. The dose of vaccine and duration since vaccination were associated with NAb positivity. The OR of two and three doses of vaccines were 7.20 and 458.33 (P < 0.05). NAb levels and duration since vaccination showed a linear relationship in pregnant women vaccinated two doses, with a decrease to a near seropositivity threshold at 22 weeks. Adverse events were mainly mild or moderate after vaccinated during pregnancy, with no increase in incidence compared with whom vaccinated during pre-pregnancy. CONCLUSIONS: The use of inactivated vaccines during pregnancy induced favorable immune persistence, and the incidence of adverse events did not increase.
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Vacunas contra la COVID-19 , COVID-19 , Embarazo , Femenino , Humanos , Vacunas contra la COVID-19/efectos adversos , Estudios Transversales , COVID-19/prevención & control , SARS-CoV-2 , Vacunación/efectos adversos , Anticuerpos Neutralizantes , Vacunas de Productos Inactivados/efectos adversos , Inmunidad , Anticuerpos AntiviralesRESUMEN
Developmental disabilities prevalence seem to be high in countries around the world. It's worth understanding the most recent prevalence and trends of developmental disabilities. The objective of this study is to examine the prevalence and trends of developmental disabilities of US children and adolescents. A total of 26,422 individuals aged 3-17 years were included. Annual data were examined from the National Health Interview Survey (2018-2021). Weighted prevalence for each of the selected developmental disabilities were calculated. The prevalence of any developmental disabilities in individuals was 16.65% (95% CI 16.03-17.26%), prevalence of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), autism spectrum disorder (ASD), intellectual disability (ID), and other developmental delay were 9.57% (95% CI 9.09-10.06%), 7.45% (95% CI 7.00-7.89%), 2.94% (95% CI 2.67-3.21%), 1.72% (95% CI 1.51-1.93%), and 5.24% (95% CI 4.89-5.59%), respectively. Significant increases were observed for other developmental delay (4.02-6.05%) and co-occurring LD & ID (1.03-1.82%). Findings form this study highlight a high prevalence of any developmental disabilities, although no significant increase was observed. The prevalence of other developmental delay and co-occurring LD & ID were significantly increased. Further investigation is warranted to assess potentially modifiable risk factors and causes of developmental disabilities.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Discapacidad Intelectual , Discapacidades para el Aprendizaje , Humanos , Niño , Adolescente , Discapacidades del Desarrollo/epidemiología , Trastorno del Espectro Autista/epidemiología , Prevalencia , Discapacidades para el Aprendizaje/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Discapacidad Intelectual/epidemiologíaRESUMEN
Objective: As a major source of added sugar, the consumption of sugar-sweetened beverages (SSBs) continues to increase worldwide. The adverse health effects associated with SSBs are also risk factors for cognitive development, but studies on the relationship between SSBs and adolescents' cognitive function are limited. We used data released by the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) to explore the association between the consumption of SSBs and cognitive function among children and adolescents aged 12-16 years in the United States. Methods and procedures: A nationally representative population sample included 1,809 adolescents aged 12-16 years who participated in the United States NHANES from 1988 to 1994 and provided samples for the dietary intake frequency questionnaire and measures of cognitive function. Binary logistic regression was used to estimate the association between the frequency of SSB consumption and scores on cognitive function tests. Results: This study of 1,809 adolescents aged 12-16 years comprised 963 girls (weighted proportion, 48.17%) and 846 boys (weighted, 51.83%), with a weighted mean (SE) age of 13.99 (0.05) years. Compared with adolescents who intake SSBs 0-1 times per week, those who drank 4-7 times per week had better scores in arithmetic, reading, and digit span tests, with odds ratios (ORs) of 0.36 (95% CI = 0.16-0.82), 0.35 (95% CI = 0.18-0.70), and 0.19 (95% CI = 0.08-0.44), respectively. The ORs for abnormal block design scores increase with the frequency of SSB intake after being adjusted for potential confounders (P for trend 0.02). Stratified analyses showed that compared with normal or below BMI, among overweight or obese individuals, the frequency of SSB intake had significant ORs for abnormal digit span scores (OR = 4.76, 95% CI = 1.19-18.96 vs. 0.35, 95% CI = 0.10-1.25; P for interaction = 0.01). Conclusion: The positive associations of SSBs at moderate level intake with better scores in arithmetic, reading, and digit span were observed, but no dose-response relationship was identified at the overall level. Additionally, with the increasing frequency of SSB consumption, the risk of anomalous block design scores increased among US adolescents. Further investigation is warranted to confirm the association and mechanism between SSBs and cognitive function among adolescents.
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PURPOSE: Hepatocellular carcinoma (HCC), a malignant tumor that exists worldwide, has a high morbidity and mortality rate. Previous studies have reported that lncRNA NR2F1-AS1 plays a critical role in several cancers. Here, we aimed to investigate the biological function of NR2F1-AS1 and its molecular mechanism in the migration and invasion of HCC. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to analyze NR2F1-AS1 expression in HCC. The biological function was investigated by transwell invasion and migration assays. The protein level was identified by Western blot. In addition, the downstream targets of NR2F1-AS1 and miR-642a were confirmed by luciferase reporter assays. RESULTS: NR2F1-AS1 was significantly upregulated in HCC and associated with the poor prognosis of HCC patients. Biological function experiments revealed that the silence of NR2F1-AS1 suppressed cell invasion and migration in HCC. More importantly, NR2F1-AS1 directly interacted with miR-642a and negatively regulated miR-642a. DEK was the target of miR-642a, and NR2F1-AS1 positively regulated DEK expression by suppressing miR-642a. CONCLUSION: Taken together, it is the first time we discovered the interaction of NR2F1-AS1 with miR-642a in modulating HCC cell invasion and migration.
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Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the treatment of PK deficiency. We demonstrate that AG-348 can increase the activity of wild-type and mutant PK enzymes in biochemical assays and in patient red blood cells treated ex vivo. These data illustrate the potential for AG-348 to restore the glycolytic pathway activity in patients with PK deficiency and ultimately lead to clinical benefit.
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Activadores de Enzimas/farmacología , Activadores de Enzimas/uso terapéutico , Eritrocitos/enzimología , Piruvato Quinasa/deficiencia , Piruvato Quinasa/metabolismo , Quinolinas/farmacología , Quinolinas/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Anemia Hemolítica Congénita no Esferocítica , Animales , Activación Enzimática/efectos de los fármacos , Activadores de Enzimas/química , Eritrocitos/efectos de los fármacos , Humanos , Cinética , Ratones , Piperazinas , Piruvato Quinasa/efectos de los fármacos , Errores Innatos del Metabolismo del Piruvato , Quinolinas/química , Proteínas Recombinantes/metabolismo , Sulfonamidas/química , Donantes de TejidosRESUMEN
Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach. We report the discovery and characterization of AG-221, an orally available, selective, potent inhibitor of the mutant IDH2 enzyme. AG-221 suppressed 2HG production and induced cellular differentiation in primary human IDH2 mutation-positive acute myeloid leukemia (AML) cells ex vivo and in xenograft mouse models. AG-221 also provided a statistically significant survival benefit in an aggressive IDH2R140Q-mutant AML xenograft mouse model. These findings supported initiation of the ongoing clinical trials of AG-221 in patients with IDH2 mutation-positive advanced hematologic malignancies.Significance: Mutations in IDH1/2 are identified in approximately 20% of patients with AML and contribute to leukemia via a block in hematopoietic cell differentiation. We have shown that the targeted inhibitor AG-221 suppresses the mutant IDH2 enzyme in multiple preclinical models and induces differentiation of malignant blasts, supporting its clinical development. Cancer Discov; 7(5); 478-93. ©2017 AACR.See related commentary by Thomas and Majeti, p. 459See related article by Shih et al., p. 494This article is highlighted in the In This Issue feature, p. 443.
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Aminopiridinas/farmacología , Antineoplásicos/farmacología , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Leucemia Mieloide Aguda/genética , Triazinas/farmacología , Animales , Línea Celular Tumoral , Humanos , Isocitrato Deshidrogenasa/genética , Ratones , Mutación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Enchondromas are benign cartilage tumors and precursors to malignant chondrosarcomas. Somatic mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2) are present in the majority of these tumor types. How these mutations cause enchondromas is unclear. Here, we identified the spectrum of IDH mutations in human enchondromas and chondrosarcomas and studied their effects in mice. A broad range of mutations was identified, including the previously unreported IDH1-R132Q mutation. These mutations harbored enzymatic activity to catalyze α-ketoglutarate to d-2-hydroxyglutarate (d-2HG). Mice expressing Idh1-R132Q in one allele in cells expressing type 2 collagen showed a disordered growth plate, with persistence of type X-expressing chondrocytes. Chondrocyte cell cultures from these animals or controls showed that there was an increase in proliferation and expression of genes characteristic of hypertrophic chondrocytes with expression of Idh1-R132Q or 2HG treatment. Col2a1-Cre;Idh1-R132Q mutant knock-in mice (mutant allele expressed in chondrocytes) did not survive after the neonatal stage. Col2a1-Cre/ERT2;Idh1-R132 mutant conditional knock-in mice, in which Cre was induced by tamoxifen after weaning, developed multiple enchondroma-like lesions. Taken together, these data show that mutant IDH or d-2HG causes persistence of chondrocytes, giving rise to rests of growth-plate cells that persist in the bone as enchondromas.