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1.
Methods Mol Biol ; 2302: 237-251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33877631

RESUMO

Molecular dynamics simulations of membrane proteins have grown dramatically in the last 20 years. Running these simulations first requires embedding the protein's three-dimensional structure in a lipid bilayer of a suitable composition, one that resembles its native environment. This step is far from trivial, especially for modeling heterogeneous mixtures of lipids. CHARMM-GUI, a webserver for simulation system preparation greatly simplifies this step, allowing for the construction of complex heterogeneous and/or asymmetric membranes. Here, we demonstrate how to use CHARMM-GUI to build the membrane for the outer-membrane protein BamA.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33836287

RESUMO

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary endpoint was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary endpoint was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.

3.
Chem Res Toxicol ; 34(4): 992-1003, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33705110

RESUMO

The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered to be two of the most important carcinogens in unburned tobacco and its smoke. They readily cause tumors in laboratory animals and are classified as "carcinogenic to humans" by the International Agency for Research on Cancer. DNA adduct formation by these two carcinogens is believed to play a critical role in tobacco carcinogenesis. Among all the DNA adducts formed by NNN and NNK, 2'-deoxyadenosine (dAdo)-derived adducts have not been fully characterized. In the study reported here, we characterized the formation of N6-[4-(3-pyridyl)-4-oxo-1-butyl]-2'-deoxyadenosine (N6-POB-dAdo) and its reduced form N6-PHB-dAdo formed by NNN 2'-hydroxylation in rat liver and lung DNA. More importantly, we characterized a new dAdo adduct N6-[4-hydroxy-1-(pyridine-3-yl)butyl]-2'-deoxyadenosine (N6-HPB-dAdo) formed after NaBH3CN or NaBH4 reduction both in vitro in calf thymus DNA reacted with 5'-acetoxy-N'-nitrosonornicotine and in vivo in rat liver and lung upon treatment with NNN. This adduct was specifically formed by NNN 5'-hydroxylation. Chemical standards of N6-HPB-dAdo and the corresponding isotopically labeled internal standard [pyridine-d4]N6-HPB-dAdo were synthesized using a four-step method. Both NMR and high-resolution mass spectrometry data agreed well with the proposed structure of N6-HPB-dAdo. The new adduct coeluted with the synthesized internal standard under various LC conditions. Its product ion patterns of MS2 and MS3 transitions were also consistent with the proposed fragmentation patterns. Chromatographic resolution of the two diastereomers of N6-HPB-dAdo was successfully achieved. Quantitation suggested a dose-dependent response of the levels of this new adduct in the liver and lung of rats treated with NNN. However, its level was lower than that of 2-[2-(3-pyridyl)-N-pyrrolidinyl]-2'-deoxyinosine, a previously reported dGuo adduct that is also formed from NNN 5'-hydroxylation. The identification of N6-HPB-dAdo in this study leads to new insights pertinent to the mechanism of carcinogenesis by NNN and to the development of biomarkers of NNN metabolic activation.

4.
Chem Res Toxicol ; 34(4): 1004-1015, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33720703

RESUMO

The International Agency for Research on Cancer has classified the tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as "carcinogenic to humans" (Group 1). To exert its carcinogenicity, NNN requires metabolic activation to form reactive intermediates which alkylate DNA. Previous studies have identified cytochrome P450-catalyzed 2'-hydroxylation and 5'-hydroxylation of NNN as major metabolic pathways, with preferential activation through the 5'-hydroxylation pathway in some cultured human tissues and patas monkeys. So far, the only DNA adducts identified from NNN 5'-hydroxylation in rat tissues are 2-[2-(3-pyridyl)-N-pyrrolidinyl]-2'-deoxyinosine (Py-Py-dI), 6-[2-(3-pyridyl)-N-pyrrolidinyl]-2'-deoxynebularine (Py-Py-dN), and N6-[4-hydroxy-1-(pyridine-3-yl)butyl]-2'-deoxyadenosine (N6-HPB-dAdo) after reduction. To expand the DNA adduct panel formed by NNN 5'-hydroxylation and identify possible activation biomarkers of NNN metabolism, we investigated the formation of dAdo-derived adducts using a new highly sensitive and specific liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry method. Two types of NNN-specific dAdo-derived adducts, N6-[5-(3-pyridyl)tetrahydrofuran-2-yl]-2'-deoxyadenosine (N6-Py-THF-dAdo) and 6-[2-(3-pyridyl)-N-pyrrolidinyl-5-hydroxy]-2'-deoxynebularine (Py-Py(OH)-dN), were observed for the first time in calf thymus DNA incubated with 5'-acetoxyNNN. More importantly, Py-Py(OH)-dN was also observed in relatively high abundance in the liver and lung DNA of rats treated with racemic NNN in the drinking water for 3 weeks. These new adducts were characterized using authentic synthesized standards. Both NMR and MS data agreed well with the proposed structures of N6-Py-THF-dAdo and Py-Py(OH)-dN. Reduction of Py-Py(OH)-dN by NaBH3CN led to the formation of Py-Py-dN both in vitro and in vivo, which was confirmed by its isotopically labeled internal standard [pyridine-d4]Py-Py-dN. The NNN-specific dAdo adducts Py-THF-dAdo and Py-Py(OH)-dN formed by NNN 5'-hydroxylation provide a more comprehensive understanding of the mechanism of DNA adduct formation by NNN.

5.
Cell Host Microbe ; 29(3): 489-502.e8, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33548198

RESUMO

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-ß levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-ß responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.


Assuntos
/imunologia , Interferon Tipo I/imunologia , /imunologia , Proteínas não Estruturais Virais/genética , Células A549 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Sequência de Bases , Linhagem Celular , Criança , Pré-Escolar , Chlorocebus aethiops , Feminino , Deleção de Genes , Genômica , Células HEK293 , Humanos , Lactente , Interferon Tipo I/sangue , Interferon beta/sangue , Interferon beta/metabolismo , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Genética Reversa , Células Vero , Proteínas não Estruturais Virais/imunologia , Adulto Jovem
7.
Am J Cardiol ; 143: 145-153, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352210

RESUMO

Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to "therapeutic" effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes ("filling out" of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with "normal" single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both "normal" and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt.


Assuntos
Aorta/crescimento & desenvolvimento , Aneurisma Aórtico/diagnóstico por imagem , Síndrome de Marfan/diagnóstico por imagem , Adolescente , Aorta/diagnóstico por imagem , Aneurisma Aórtico/tratamento farmacológico , Aneurisma Aórtico/etiologia , Índice de Massa Corporal , Superfície Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Ecocardiografia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde
8.
BMC Pulm Med ; 20(1): 323, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308175

RESUMO

BACKGROUND: Interstitial lung diseases (ILDs), a diverse group of diffuse lung diseases, mainly affect the lung parenchyma. The low-throughput 'omics' technologies (genomics, transcriptomics, proteomics) and relative drug information have begun to reshaped our understanding of ILDs, whereas, these data are scattered among massive references and are difficult to be fully exploited. Therefore, we manually mined and summarized these data at a database (ILDGDB, http://ildgdb.org/ ) and will continue to update it in the future. MAIN BODY: The current version of ILDGDB incorporates 2018 entries representing 20 ILDs and over 600 genes obtained from over 3000 articles in four species. Each entry contains detailed information, including species, disease type, detailed description of gene (e.g. official symbol of gene), and the original reference etc. ILDGDB is free, and provides a user-friendly web page. Users can easily search for genes of interest, view their expression pattern and detailed information, manage genes sets and submit novel ILDs-gene association. CONCLUSION: The main principle behind ILDGDB's design is to provide an exploratory platform, with minimum filtering and interpretation, while making the presentation of the data very accessible, which will provide great help for researchers to decipher gene mechanisms and improve the prevention, diagnosis and therapy of ILDs.


Assuntos
Bases de Dados Genéticas , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/metabolismo , Animais , Genômica , Humanos , Internet , Proteômica , Transcriptoma
9.
Artigo em Inglês | MEDLINE | ID: mdl-33374014

RESUMO

OBJECTIVES: The German Registry of Acute Aortic Dissection Type A (GERAADA) score to predict 30-day mortality in patients suffering from acute aortic dissection type A (AADA) was recently introduced. The aim of this study was to evaluate if the GERAADA score's prediction corresponds with the authors' institutional results. METHODS: All consecutive AADA patients between 2010 and 2020 were included. Retrospective data collection comprised 11 preoperative parameters: age, sex, previous cardiac surgery, inotropic support at referral, resuscitation before surgery, aortic regurgitation, preoperative hemiparesis, intubation/ventilation at referral, preoperative organ malperfusion, extension of aortic dissection and location of primary entry site. Calculations of the GERAADA score were individually performed by a cardiac surgeon blinded to the study for all patients via a web-based application (https://www.dgthg.de/de/GERAADA_Score). RESULTS: A total of 371 AADA patients were operated at the authors' institution. The mean age was 62.7 ± 13.5 years and 233 (63%) were males. Prediction of 30-day mortality was accurate for the entire study cohort (actual vs predicted 30-day mortality: 15.1% vs 15.7%; P = 0.776) as well as for all 26 subgroups. In addition, preoperative resuscitation (P < 0.001), advanced age (P = 0.042) and other/unknown malperfusion (P = 0.032) were identified as independent risk factors. CONCLUSIONS: The GERAADA score prediction of 30-day mortality after surgery is accurate, easily accessible due to its web-based platform and can be calculated with very basic preoperative clinical parameters. A prospective clinical trial is required to further evaluate the new GERAADA score as a useful tool to allow for improved decision-making in the emergency setting of AADA.

10.
Ann Vasc Surg ; 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33373766

RESUMO

BACKGROUND: This study aimed to review short- and long-term outcomes of all carotid artery stenting (CAS) in patients with radiation-induced (RI) internal carotid artery (ICA) stenosis compared with patients with atherosclerotic stenosis (AS). METHODS: We performed a single-center, multisite case-control study of transfemoral carotid artery intervention in patients stented for RI or AS. Cases of stented RI carotid arteries were identified using a CAS database covering January 2000 to December 2019. These patients were randomly matched 2:1 with stented patients because of AS by age, sex, and year of CAS. A conditional logistic regression model was performed to estimate the odds of reintervention in the RI group. Finally, a systematic review was performed to assess the outcomes of RI stenosis treated with CAS. RESULTS: There were 120 CAS in 113 patients because of RI ICA stenosis. Eighty-nine patients (78.8%) were male, and 68 patients (60.2%) were symptomatic. The reasons for radiation included most commonly treatment for diverse malignancies of the head and neck in 109 patients (96.5%). The mean radiation dose was 58.9 ± 15.6 Gy, and the time from radiation to CAS was 175.3 ± 140.4 months. Symptoms included 31 transient ischemic attacks (TIAs), 21 strokes (7 acute and 14 subacute), and 17 amaurosis fugax. The mean National Institutes of Health Stroke Scale in acute strokes was 8.7 ± 11.2. In asymptomatic patients, the indication for CAS was high-grade stenosis determined by duplex ultrasound. All CAS were successfully completed. Reinterventions were more frequent in the RI ICA stenosis cohort compared with the AS cohort (10.1% vs. 1.4%). Reinterventions occurred in 14 vessels, and causes for reintervention were restenosis in 12 followed by TIA/stroke in two vessels. On conditional regression modeling, patients with RI ICA stenosis were at a higher risk for reintervention (odds ratio = 7.1, 95% confidence interval = 2.1-32.8; P = 0.004). The mean follow-up was 33.7 ± 36.9 months, and the mortality across groups was no different (P = 0.12). CONCLUSIONS: In our single-center, multisite cohort study, patients who underwent CAS for RI ICA stenosis experienced a higher rate of restenosis and a higher number of reinterventions compared with CAS for AS. Although CAS is safe and effective for this RI ICA stenosis cohort, further data are needed to reduce the risk of restenosis, and close patient surveillance is warranted. In our systematic review, CAS was considered an excellent alternative option for the treatment of patients with RI ICA stenosis. However, careful patient selection is warranted because of the increased risk of restenosis on long-term follow-up.

11.
Phlebology ; : 268355520972923, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176592

RESUMO

BACKGROUND: To review long-term outcomes and saphenous vein (SV) occlusion rate after endovenous ablation (EVA) for symptomatic varicose veins. METHODS: A review of our EVA database (1998-2018) with at least 3-years of clinical and sonographic follow-up. The primary end point was SV closure rate. RESULTS: 542 limbs were evaluated. 358 limbs had radiofrequency and 323 limbs had laser ablations; 542 great saphenous veins (GSV), 106 small saphenous veins (SSV) and 33 anterior accessory saphenous veins (AASV) were treated. Follow-up was 5.6 ± 2.3 years; 508 (74.6%) veins were occluded, 53 (7.8%) partially occluded and 120 (17.6%) were patent. On multivariable Cox regression analysis, male sex (HR 1.6, 95% CI [0.46-018], p = 0.012) and use anticoagulation (HR 2.0, 95% CI [0.69-0.34], p = 0.044) were predictors of long-term failure. On Kaplan-Meier curve, we had an 86.3% occlusion rate. CONCLUSION: Our experience revealed a 5-year closure rate of 86.3%. Ablations have satisfactory occlusion rate.

12.
Respiration ; 99(9): 739-747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33207356

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global emerging infectious disease. OBJECTIVES: To analyze the initial clinical characteristics of COVID-19 suspected and confirmed patients on admission in order to find out which kinds may be more likely to get positive nucleic acid testing results, and to explore the risk factors associated with all-cause death. METHODS: Medical records from 309 highly suspected cases with pneumonia were collected from February 13, 2020, to March 14, 2020, in a COVID-19-designated hospital of Wuhan. The majority of the clinical data were collected on the first day of hospital admission. RESULTS: Of 309 patients with median age 64 years (interquartile ranges [IQR], 53-72 years), 111 patients (35.9%) were confirmed by nucleic acid testing (median age 64 years, IQR: 56-71 years; 48 males). Of those 111 patients, 13 (11.7%) patients died. In multivariate analysis, factors associated with positive testing included fatigue (odds ratios [OR] = 3.14; 95% confidence interval [CI]: 1.88-5.24, p < 0.001), cough (OR = 0.55; 95% CI: 0.32-0.95, p = 0.032), no less than 1 comorbidity (OR = 1.77; 95% CI: 1.06-2.98, p = 0.030), and severe pneumonia (OR = 2.67; 95% CI: 1.20-5.97, p = 0.016). Furthermore, age, dyspnea, noneffective antibiotic treatment, white blood cell, lymphocyte, platelets, and organ dysfunction (e.g., higher lactate dehydrogenase) were significantly associated with all-cause in-hospital death in patients with COVID-19. CONCLUSION: Patients with severe forms of this disease were more likely to get positive results. Age and organ dysfunction were associated with a greater risk of death.

13.
Nat Commun ; 11(1): 5202, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060590

RESUMO

Winter Eurasian cooling after the mid-1990s has been verified by numerous studies, although in recent decades, the mid-latitudes of the Northern Hemisphere have been rapidly warming globally. Because the cooling is not uniform at different spatial and temporal scales, over time, this change may not truly reflect the nature of climate fluctuations. Here, by using three types of data (reanalysis, weather station, and remote sensing image data) to assess variations in Eurasian seasonal cooling, we examine the causes of these changes. During a 30-year climatology (1989-2018), we show that a significant (P < 0.05) abrupt change in the autumn Eurasian air temperature trend occurred in 2003. Our results suggest that from 2004-2018, the autumn Eurasian temperature reveals a significant cooling trend (P < 0.05). We demonstrate that the autumn cooling in Eurasia is likely influenced by the Pacific Decadal Oscillation (PDO) and Siberian high (SH). Since 2004, the strengthening of the PDO and SH explains approximately 54% and 18% of the autumn cooling in Eurasia, respectively. We also find that the cooling in autumn is stronger than that in winter.

14.
Ann Thorac Surg ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075319

RESUMO

BACKGROUND: This study evaluates sex differences in the natural history of descending thoracic and thoracoabdominal aortic aneurysms (DTTAAs). METHODS: 907 patients with descending thoracic/thoracoabdominal aortic sizes > 3cm were retrospectively reviewed. Growth rate estimates were performed utilizing an instrumental variables approach. Yearly complication rates as a function of aortic size were computed. RESULTS: There were 615 (67.8%) males and 292 (32.2%) females (treated between 1990 and 2018), with mean aortic diameters of 4.1±1.4cm and 4.8±1.6cm, respectively (p < 0 .001). The mean growth rate of DTTAAs was 0.17cm/year in males and 0.25cm/year in females (p < 0 .001), increasing with increasing aneurysm size. Dissection, rupture, or aortic death, or the combination of the three occurred at double the rate for females compared to males (5.8 vs. 2.3 %/ year for the combined endpoint). . DTTAA diameter >5cm was associated with 26.3% (male) and 33.1% (female) average yearly rates of the composite end-point of rupture, dissection, and death (P<0.05). The probability of fatal complications (rupture and death) increased sharply at 5.75 cm in both sexes. Between 4.5-5.75cm, there was another hinge point of higher probability of fatal complications in females. CONCLUSIONS: Women diagnosed with DTTAA fare worse. Faster aneurysm growth and higher rates of dissection, rupture, and aortic death are apparent in women. Current guidelines recommend surgical intervention at 5.5-6.0cm for DTTAAs without gender considerations. Our findings suggest that increased virulence of DTTAA in women may indicate surgery at a somewhat smaller diameter.

15.
BMC Surg ; 20(1): 249, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092557

RESUMO

BACKGROUND: With the mature application of laparoscopy in hepatobiliary surgery, laparoscopic treatment of hepatic cystic echinococcosis (CE) has made certain progress. But, due to the inherent limitations of laparoscopy and the growth characteristics of cystic echinococcosis, distinguishing the boundary between cystic lesion and normal hepatic parenchyma is pivotal importance for successful surgery. Indocyanine green (ICG) fluorescence imaging technology can view the boundary of lesion and normal tissue during the treatment of hepatic cystic echinococcosis. Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis may be an effective surgical strategy. METHODS: The clinical data contained nine patients with hepatic cystic echinococcosis who underwent laparoscopic surgery with indocyanine green fluorescence imaging technique in authors' institution from December 2018 to December 2019 were retrospectively analyzed. Indocyanine green was administered intravenously three days prior to surgery. The fluorescence acquisition system for real-time imaging was used during the surgery and the patients were followed up after surgery. RESULTS: Of reported nine patients, six are male and the remaining three are female. The average age is (36.4 ± 7.6) years. For all subjects, surgical procedures were performed under laparoscopy with indocyanine green fluorescence system. This technique showed the clear boundary of the hepatic cyst with normal liver parenchyma. Total cystectomy in six patients, subtotal cystectomy in two patients and partial hepatectomy in one patient were performed respectively. The average operation time was 3.8 ± 0.9 h, blood loss 206.0 ± 120.7 ml. Neither blood transfusion nor post-operative complication was experienced. The average abdominal drainage time was 3.4 ± 0.9 days with hospital stay 5.7 ± 2.1 days. During the 6-12 months follow-up period, neither recurrence nor intraperitoneal implantation was found. CONCLUSIONS: Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis is safe and feasible. Enhanced boundary image can assist surgeons to complete radical resection and reduce complications.

16.
Expert Rev Gastroenterol Hepatol ; : 1-19, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33121300

RESUMO

INTRODUCTION: Early gastric cancer (EGC) is a well-defined gastric malignancy that is limited to the mucosa or submucosa, irrespective of lymph node metastasis. At an early stage, gastric cancer often does not cause symptoms until it becomes advanced, and it is a heterogeneous disease and usually encountered in its late stages. AREA COVERED: This comprehensive review will provide a novel insight into the evaluation of EGC epidemiology, defining terms, extensive etiology and risk factors, and timely diagnosis since prevention is an essential approach for controlling this cancer and reducing its morbidity and mortality. EXPERT OPINION: The causative manner of EGC is complex and multifactorial. In recent years, researchers have made significant contributions to understanding the etiology and pathogenesis of EGC, and standardization in the evaluation of disease activity. Though the incidence of this cancer is steadily declining in some advanced societies owing to appropriate interventions, there remains a serious threat to health in developing nations. Early detection of resectable gastric cancer is crucial for better patient outcomes.

17.
ACS Sens ; 5(10): 3031-3036, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32935538

RESUMO

Conventional flow cytometry has been widely used for high-throughput single-cell gene expression analysis using specific antibody staining. However, this is limited by the availability of high-quality antibodies. We developed a novel flow cytometry RNA detection technique termed RCA-Flow for single-cell RNA expression analysis. We showed that it is able to analyze not only mRNAs but also microRNAs and circular RNAs that are otherwise difficult to analyze by other flow cytometry techniques. The versatility for high-throughput analysis of different types of RNA molecules makes our method possess great potential for both biomedical and clinical applications.

18.
Epidemiol Infect ; 148: e211, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900409

RESUMO

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56-71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911-1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563-0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.


Assuntos
Betacoronavirus , Plaquetas , Infecções por Coronavirus/mortalidade , Linfócitos , Neutrófilos , Pneumonia Viral/mortalidade , Adolescente , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Infecções por Coronavirus/sangue , Infecções por Coronavirus/etiologia , Humanos , Lactente , Recém-Nascido , Pacientes Internados , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Am J Cardiol ; 129: 71-78, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32605717

RESUMO

Controversy persists regarding the advisability of anticoagulation for the early period after biological surgical aortic valve replacement (AVR). We aim to examine the impact of various antithrombotic regimens on outcomes in a large cohort of biological AVR patients. Records of 1,111 consecutive adult patients who underwent surgical biological AVR at our institution between 2013 and 2017 were reviewed. Outcomes included stroke, bleeding, and death at 3 and 12 months. Treatment regimens included (1) no therapy, (2) anticoagulants (warfarin or Factor Xa inhibitors), (2) antiplateles (various), and (4) anticoagulants + antiplatelets. Kaplan-Meier analysis was used to track outcomes, and Cox-proportional hazards regression models were conducted to analyze effects of different therapies on adverse events. At 3 months, thromboembolic events were low and not significantly different between the no therapy group (2.2%) and anticoagulation (2.8%) or anticoagulation + antiplatelet (3.6%) or all groups (3.7%). The antiplatelet group was just significantly lower, at 2.2%. However, this was driven by non-stroke cardiovascular events in patients with coronary artery disease. The incidence of death at 3 months was low and not significantly different between all groups. At 12 months, there were no thromboembolic benefits between groups, but bleeding events were significantly higher in the anticoagulation group (no therapy (1.4%), anticoagulation (8.4%), antiplatelet (4.5%), anticoagulation + antiplatelet (7.9%)). In conclusion, none of the antithrombotic regimens showed benefits in stroke or survival at 3 or 12 months after biological AVR. Anticoagulation increased bleeding events. Routine anticoagulation after biological AVR appears to be unnecessary and potentially harmful.


Assuntos
Anticoagulantes/uso terapêutico , Estenose da Valva Aórtica/cirurgia , Bioprótese , Próteses Valvulares Cardíacas , Hemorragia/epidemiologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/anormalidades , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Hemorragia/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Cuidados Pós-Operatórios , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Varfarina/uso terapêutico , Adulto Jovem
20.
J Int Med Res ; 48(6): 300060520934635, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32588693

RESUMO

OBJECTIVE: Interventions for hyperinsulinemia (HINS), an early indicator of type 2 diabetes mellitus (T2DM), can significantly reduce the T2DM risk. This study aims to determine how dipeptidyl peptidase-4 (DPP-4) inhibition prevents HINS progression to T2DM through ameliorating hepatic steatosis. METHODS: KKay mice were used as a HINS model and they underwent exercise or received a DPP-4 inhibitor, MK0626. Hepatic steatosis was examined and liver diacylglycerol levels were determined. Human hepatic cells (LO2) were treated with MK0626 or transfected with DPP-4 siRNA. Protein kinase C ε isoform (PKCε) and DPP-4 expression and insulin receptor substrate 1 (IRS-1) phosphorylation were assessed using immunohistochemistry and western blot. RESULTS: KKay mice developed HINS spontaneously at 7 weeks of age. Similar to exercise, MK0626 ameliorated hepatic steatosis and reduced the liver triglyceride and diacylglycerol content. Both exercise and MK0626 suppressed diacylglycerol-induced PKCε expression and restored insulin signaling, which was shown by tyrosine phosphorylation of IRS-1, in the livers of KKay mice. Additionally, silencing DPP-4 or MK0626 treatment decreased PKCε expression in LO2 cells. CONCLUSIONS: Our data demonstrate that DPP-4 inhibition resembles exercise and effectively delays T2DM onset by suppressing hepatic PKCε expression in the HINS mouse model.

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