RESUMO
The Periodic Law of Chemistry is one of the great discoveries in cultural history. Elements behaving chemically similar are empirically merged in groups G of a Periodic Table, each element with G valence electrons per neutral atom, and with upper limit G for the oxidation and valence numbers. Here, we report that among the usually mono- or di-valent s-block elements (G = 1 or 2), the heaviest members (87Fr, 88Ra, 119E, and 120E) with atomic numbers Z = 87, 88, 119, 120 form unusual 5- or 6-valent compounds at ambient conditions. Together with well-reported basic changes of valence at the end of the 6d-series, in the whole 7p-series, and for 5g6f-elements, it indicates that at the bottom of common Periodic Tables, the classic Periodic Law is not as straightforward as commonly expected. Specifically, we predict the feasible experimental synthesis of polyvalent [RaL-n] (n = 4, 6) compounds.
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Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.
Assuntos
Consumo de Bebidas Alcoólicas , Bancos de Espécimes Biológicos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Distúrbios do Início e da Manutenção do Sono , Sono , Humanos , Análise da Randomização Mendeliana/métodos , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/epidemiologia , Masculino , Reino Unido/epidemiologia , Feminino , Pessoa de Meia-Idade , Sono/genética , Sono/fisiologia , Idoso , Distúrbios do Início e da Manutenção do Sono/genética , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Ronco/genética , Ronco/epidemiologia , Adulto , Fenótipo , Transtornos do Sono-Vigília/genética , Transtornos do Sono-Vigília/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Biobanco do Reino UnidoRESUMO
Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histocompatibility complex (MHC) class I antigen-presentation to CD8 T cells in establishing cerebral malaria pathology, we developed novel H-2Kb LoxP and H-2Db LoxP mice crossed with Cdh5-Cre mice to achieve targeted deletion of discrete class I molecules, specifically from brain endothelium. This strategy allowed us to avoid off-target effects on iron homeostasis and class I-like molecules, which are known to perturb Plasmodium infection. This is the first endothelial-specific ablation of individual class-I molecules enabling us to interrogate these molecular interactions. In these studies, we interrogated human and mouse transcriptomics data to compare antigen presentation capacity during cerebral malaria. Using the Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we observed that H-2Kb and H-2Db class I molecules regulate distinct patterns of disease onset, CD8 T-cell infiltration, targeted cell death and regional blood-brain barrier disruption. Strikingly, ablation of either molecule from brain endothelial cells resulted in reduced CD8 T-cell activation, attenuated T-cell interaction with brain vasculature, lessened targeted cell death, preserved blood-brain barrier integrity and prevention of ECM and the death of the animal. We were able to show that these events were brain-specific through the use of parabiosis and created the novel technique of dual small animal MRI to simultaneously scan conjoined parabionts during infection. These data demonstrate that interactions of CD8 T cells with discrete MHC class I molecules on brain endothelium differentially regulate development of ECM neuropathology. Therefore, targeting MHC class I interactions therapeutically may hold potential for treatment of cases of severe malaria.
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Malária Cerebral , Camundongos , Humanos , Animais , Malária Cerebral/patologia , Malária Cerebral/prevenção & controle , Células Endoteliais/patologia , Encéfalo/patologia , Barreira Hematoencefálica/patologia , Linfócitos T CD8-Positivos , Endotélio/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
A comprehensive molecular analysis of the deep-sea blind lobsters of the family Polychelidae, often referred to as "living fossils", is conducted based on all six modern genera and 27 of the 38 extant species. Using six genetic markers from both mitochondrial and nuclear genomes, the molecular phylogenetic results differ considerably from previous morphological analyses and reveal the genera Polycheles and Pentacheles to be para- or polyphyletic. As the splitting of Polycheles has strong support from both molecular and morphological data, two new genera, Dianecheles and Neopolycheles, are erected for those species excluded from the clade containing the type species of Polycheles. The pattern of polyphyly of Pentacheles, however, is not robustly resolved, so it is retained as a single genus. Fossil evidence suggests that fossil polychelids inhabited deep-sea environments as early as the Early to Middle Jurassic, demonstrating the enduring adaptation of extant polychelid species to the deep-sea. Time-calibrated phylogeny suggested that modern polychelids probably had an Atlantic origin during the Jurassic period. Since their emergence, this ancient lobster group has continued to diversify, particularly in the West Pacific, and has colonized the abyssal zone, with the deepest genus, Willemoesia, representing the more 'derived' members among extant polychelids. Differences in eye reduction among extant polychelid genera highlight the necessity for ongoing investigations to ascertain the relative degree of functionality of their eyes, if they indeed retain any function.
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Decápodes , Fósseis , Animais , Filogenia , Nephropidae , Decápodes/genéticaRESUMO
Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 µM (ascorbic acid, EC50 = 7.81 µM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 µM, respectively (acarbose, IC50 = 301.93 µM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 µM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 µM.
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Basidiomycota , Neoplasias Hematológicas , Humanos , Fungos/química , Antioxidantes/farmacologia , Antioxidantes/química , Espectroscopia de Ressonância Magnética/métodos , Estrutura MolecularRESUMO
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. METHODS: This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. RESULTS: No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. CONCLUSIONS: These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.
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Estimulação Encefálica Profunda , Modelos Animais de Doenças , Oxidopamina , Núcleo Subtalâmico , Animais , Oxidopamina/farmacologia , Masculino , Comportamento Animal/fisiologia , Transtornos Parkinsonianos/terapia , Transtornos Parkinsonianos/fisiopatologia , Ansiedade/etiologia , Ansiedade/fisiopatologia , Ratos , Ratos Sprague-Dawley , Aprendizagem da Esquiva/fisiologia , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologiaRESUMO
Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1-3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC50) values ranging from 1.2 to 22.5 µM.
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Anti-Infecciosos , Antineoplásicos , Diterpenos , Neoplasias Hematológicas , Neoplasias , Streptomyces , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antineoplásicos/uso terapêutico , Diterpenos/química , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: To examine behavior changes among formal caregivers in Taiwanese long-term care facilities (LTCFs) after receiving training in function-focused care for cognitive impairment (FFC-CI). METHOD: The current study was a clustered randomized controlled trial. Formal caregivers (i.e., RNs and nursing assistants) (N = 98) from four LTCFs were randomly assigned to experimental or control groups. Training was based on four components of FFC-CI. Data were collected four times within 9 months using five observational outcome measurements: Self-Efficacy for Restorative Care (SERCS), Outcome Expectations for Restorative Care Scale (OERCS), Restorative Care Knowledge Scale (RCKS), Restorative Care Behavior Checklist (RCBC), and Job Attitude Scale (JAS). RESULTS: Statistically significant changes were noted in each activity of restorative care behavior among the four observational measurements. Results also indicated that job satisfaction was a statistically significant main effect for the experimental group; however, SERCS, OERCS, and RCKS scores were not statistically significant. CONCLUSION: To eliminate gaps between translating research outcomes to clinical practice, this study applied a theory-based caring model for caregivers to improve knowledge and skills in caring for older adults with dementia. Caregivers who received training in FFC-CI not only had higher job satisfaction but could also provide specific FFC activities for residents during their daily care. [Journal of Gerontological Nursing, 50(7), 42-50.].
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Cuidadores , Disfunção Cognitiva , Assistência de Longa Duração , Humanos , Taiwan , Masculino , Feminino , Cuidadores/psicologia , Cuidadores/educação , Pessoa de Meia-Idade , Adulto , Disfunção Cognitiva/enfermagem , Disfunção Cognitiva/terapia , Idoso , Casas de Saúde , Assistentes de Enfermagem/psicologia , Assistentes de Enfermagem/educaçãoRESUMO
A nursing experience supporting parents experiencing anxiety related to their 26+2 weeks preterm infant on continued ventilator assistance at home due to bronchopulmonary dysplasia is described in this article. Data were collected from March 21st to June 1st, 2021 via observation, interviews, clinical care, medical record reviews, and discharge preparation services. A holistic nursing assessment identified the main health issues as: gas exchange disorder, inefficient infant feeding patterns, and caregiver role stress. The parents were encouraged to participate in care activities, create individualized discharge plans, and view health education videos and caregiving skill demonstrations. Kangaroo care, comfortable positioning and soothing techniques were used to stabilize the emotions of the infant and to strengthen the parent-child bond. Psychological support was provided to alleviate parental anxiety and to enhance parenting ability and confidence. This experience supports the importance of tailoring clinical care to individual needs, adopting a family-centered approach, assessing family interactions, and making early preparations to obtain appropriate continuous care after discharge to ensure proper continuum of care.
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Displasia Broncopulmonar , Recém-Nascido Prematuro , Humanos , Recém-Nascido , Displasia Broncopulmonar/enfermagemRESUMO
BACKGROUND: Olfactory ensheathing cells (OECs) serve as a bridge by migrating at the site of spinal cord injury (SCI) to facilitate the repair of the neural structure and neural function. However, OEC migration at the injury site not only faces the complex and disordered internal environment but also is closely associated with the migration ability of OECs. METHODS: We extracted OECs from the olfactory bulb of SD rats aged <7 days old. We verified the micro ribonucleic acid (miR)-145a-5p expression level in the gene chip after SCI and OEC transplantation using quantitative reverse transcription (qRT)-polymerase chain reaction (PCR). The possible target gene Plexin-A2 of miR-145a-5p was screened using bioinformatics and was verified using dual-luciferase reporter assay, Western blot, and qRT-PCR. The effect of miR-145a-5p/plexin-A2 on OEC migration ability was verified by wound healing assay, Transwell cell migration assay, and immunohistochemistry. Nerve repair was observed at the injured site of the spinal cord after OEC transplantation using tissue immunofluorescence and magnetic resonance imaging, diffusion tensor imaging, and the Basso-Beattie-Bresnahan locomotor rating scale were further used for imaging and functional evaluation. RESULTS: miR-145a-5p expression in the injured spinal cord tissue after SCI considerably decreased, while Plexin-A2 expression significantly increased. OEC transplantation can reverse miR-145a-5p and Plexin-A2 expression after SCI. miR-145a-5p overexpression enhanced the intrinsic migration ability of OECs. As a target gene of miR-145a-5p, Plexin-A2 hinders OEC migration. OEC transplantation overexpressing miR-145a-5p after SCI can increase miR-145a-5p levels in the spinal cord, reduce Plexin-A2 expression in the OECs and the spinal cord tissue, and promote OEC migration and distribution at the injured site. OEC transplantation overexpressing miR-145a-5p can promote the repair of neural morphology and neural function. CONCLUSIONS: Our study demonstrated that miR-145a-5p could promote OEC migration by down-regulating the target gene Plexin-A2, and transplantation of miR-145a-5p engineered OECs was beneficial to enhance neural structural and functional recovery in SCI rats.
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MicroRNAs , Traumatismos da Medula Espinal , Ratos , Animais , Ratos Sprague-Dawley , Imagem de Tensor de Difusão , Traumatismos da Medula Espinal/metabolismo , Bulbo Olfatório/patologia , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
OBJECTIVE: To evaluate the impact of post-diagnostic metformin or statin use and duration on risk of biochemical recurrence in a racially-diverse cohort of Veterans. METHODS: The population consisted of men diagnosed with prostate cancer in the Veterans Health Administration and treated with either radical prostatectomy or radiation (Full cohort n = 65,759, Black men n = 18,817, White men n = 46,631, Other = 311). The association between post-diagnostic (1) metformin and (2) statin use with biochemical recurrence was assessed using multivariable, time-varying Cox Proportional Hazard Models for the overall cohort and by race. In a secondary analysis, metformin and statin duration were evaluated. RESULTS: Post-diagnostic metformin use was not associated with biochemical recurrence (multivariable-adjusted hazard ratio [aHR]: 1.01; 95% confidence interval [CI]: 0.94, 1.09), with similar results observed for both Black and White men. However, duration of metformin use was associated with a reduced risk of biochemical recurrence in the cohort overall (HR: 0.94; 95% CI: 0.92, 0.95) as well as both Black and White men. By contrast, statin use was associated with a reduced risk of biochemical recurrence (HR: 0.83; 95% CI: 0.79, 0.88) in the overall cohort as well as both White and Black men. Duration of statin use was also inversely associated with biochemical recurrence in all groups. CONCLUSION: Post-diagnostic metformin and statin use have the potential to prevent biochemical recurrence in men diagnosed with prostate cancer.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Metformina , Neoplasias da Próstata , Veteranos , Masculino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metformina/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/cirurgia , Prostatectomia/métodosRESUMO
To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid amplification test positive [NAT+, n = 2331] or antibody positive (Ab+)/NAT- [n = 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Ab+/NAT- (aHR = 0.91; 95% confidence interval [CI], 0.75-1.10) and HCV NAT+ (aHR = 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NAT+ kidneys were associated with a higher 1-year estimated glomerular filtration (63.0 vs 61.0 mL/min/1.73 m2, P = .007) and lower risk of delayed graft function (aOR = 0.76; 95% CI, 0.68-0.84) compared with HCV-negative kidneys. Our findings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.
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Hepatite C Crônica , Hepatite C , Transplante de Rim , Humanos , Hepacivirus , Transplante de Rim/efeitos adversos , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Doadores de TecidosRESUMO
There is a chronic shortage of donor lungs for pulmonary transplantation due, in part, to low lung utilization rates in the United States. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients database (2006-2019) and developed the lung donor (LUNDON) acceptability score. A total of 83 219 brain-dead donors were included and were randomly divided into derivation (n = 58 314, 70%) and validation (n = 24 905, 30%) cohorts. The overall lung acceptance was 27.3% (n = 22 767). Donor factors associated with the lung acceptance were age, maximum creatinine, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, mechanism of death by asphyxiation or drowning, history of cigarette use (≥20 pack-years), history of myocardial infarction, chest x-ray appearance, bloodstream infection, and the occurrence of cardiac arrest after brain death. The prediction model had high discriminatory power (C statistic, 0.891; 95% confidence interval, 0.886-0.895) in the validation cohort. We developed a web-based, user-friendly tool (available at https://sites.wustl.edu/lundon) that provides the predicted probability of donor lung acceptance. LUNDON score was also associated with recipient survival in patients with high lung allocation scores. In conclusion, the multivariable LUNDON score uses readily available donor characteristics to reliably predict lung acceptability. Widespread adoption of this model may standardize lung donor evaluation and improve lung utilization rates.
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Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Humanos , Adulto Jovem , Adulto , Estudos Retrospectivos , Doadores de Tecidos , Pulmão , Morte EncefálicaRESUMO
OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Bases de Dados FactuaisRESUMO
OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Abandono do Hábito de Fumar , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
OBJECTIVE: The aim was to develop and validate the Veterans Administration (VA) Lung Cancer Mortality (VALCAN-M) score, a risk prediction model for 90-day mortality following surgical treatment of clinical stage I nonsmall-cell lung cancer (NSCLC). BACKGROUND: While surgery remains the preferred treatment for functionally fit patients with early-stage NSCLC, less invasive, nonsurgical treatments have emerged for high-risk patients. Accurate risk prediction models for postoperative mortality may aid surgeons and other providers in optimizing patient-centered treatment plans. METHODS: We performed a retrospective cohort study using a uniquely compiled VA data set including all Veterans with clinical stage I NSCLC undergoing surgical treatment between 2006 and 2016. Patients were randomly split into derivation and validation cohorts. We derived the VALCAN-M score based on multivariable logistic regression modeling of patient and treatment variables and 90-day mortality. RESULTS: A total of 9749 patients were included (derivation cohort: n=6825, 70.0%; validation cohort: n=2924, 30.0%). The 90-day mortality rate was 4.0% (n=390). The final multivariable model included 11 factors that were associated with 90-day mortality: age, body mass index, history of heart failure, forced expiratory volume (% predicted), history of peripheral vascular disease, functional status, delayed surgery, American Society of Anesthesiology performance status, tumor histology, extent of resection (lobectomy, wedge, segmentectomy, or pneumonectomy), and surgical approach (minimally invasive or open). The c statistic was 0.739 (95% CI=0.708-0.771) in the derivation cohort. CONCLUSIONS: The VALCAN-M score uses readily available treatment-related variables to reliably predict 90-day operative mortality. This score can aid surgeons and other providers in objectively discussing operative risk among high-risk patients with clinical stage I NSCLC considering surgery versus other definitive therapies.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Pulmão , Pneumonectomia/efeitos adversos , Fatores de Risco , Resultado do TratamentoRESUMO
We report the development of a reproducible and highly sensitive surface-enhanced Raman scattering (SERS) substrate using a butanol-induced self-assembly of gold nanoparticles (AuNPs) and its application as a rapid diagnostic platform for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The butanol-induced self-assembly process was used to generate a uniform assembly of AuNPs, with multiple hotspots, to achieve high reproducibility. When an aqueous droplet containing AuNPs and target DNAs was dropped onto a butanol droplet, butanol-induced dehydration occurred, enriching the target DNAs around the AuNPs and increasing the loading density of the DNAs on the AuNP surface. The SERS substrate was evaluated by using Raman spectroscopy, which showed strong electromagnetic enhancement of the Raman signals. The substrate was then tested for the detection of SARS-CoV-2 using SERS, and a very low limit of detection (LoD) of 3.1 × 10-15 M was obtained. This provides sufficient sensitivity for the SARS-CoV-2 screening assay, and the diagnostic time is significantly reduced as no thermocycling steps are required. This study demonstrates a method for the butanol-induced self-assembly of AuNPs and its application as a highly sensitive and reproducible SERS substrate for the rapid detection of SARS-CoV-2. The results suggest the potential of this approach for developing rapid diagnostic platforms for other biomolecules and infectious diseases.
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COVID-19 , Nanopartículas Metálicas , Humanos , Butanóis , Ouro , SARS-CoV-2 , Desidratação , Reprodutibilidade dos Testes , COVID-19/diagnóstico , 1-ButanolRESUMO
PURPOSE: Our purpose was to study the accuracy of dynamic computed tomography angiography (d-CTA) in characterizing endoleak type, inflow vessels as compared with digital subtraction angiography (DSA) using qualitative and quantitative analysis. METHODS: Between March 2019 and January 2021, all patients who underwent d-CTA imaging after EVAR were retrospectively reviewed. Two blinded independent reviewers qualitatively reviewed d-CTA and DSA images. Quantitative region of interest (ROI) analysis was performed by measuring time-resolved contrast enhancement within the aorta and endoleak lesion(s) in the aneurysm sac. Differences between time-to-peak enhancement (Δ TTP) across different ROIs were quantified. RESULTS: A total of 48 patients underwent d-CTA during the study period, of whom 24 patients had abdominal EVAR and DSA imaging for comparison. Qualitative review of DSA imaging showed type I (n=4), type II (n=16), and type III (n=2) and no endoleak (n=2). In 23 of 24 patients (95.8%), d-CTA findings correlated with DSA findings for endoleak type. One patient had a type III endoleak that was demonstrated only in d-CTA (arising from defect in polymer sealing ring of Ovation stent graft) imaging. In type II endoleak cases, d-CTA identified more inflow vessels than DSA imaging (33 vs 21 vessels, p=0.010). Quantitative analysis showed mean (±SD) Δ TTP values for type I endoleak as 1.8 (±1.8) seconds, type II as 9.6 (±3.5) seconds, and for type III endoleak as 5.6 (±1.3) seconds. CONCLUSION: Dynamic CTA can accurately characterize aortic endoleak type, inflow vessels as compared with DSA imaging. Quantitative parameters such as Δ TTP enhancement can help better differentiate endoleak types and provide an objective approach to endoleak diagnosis.
Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Angiografia por Tomografia Computadorizada , Aortografia/métodos , Estudos Retrospectivos , Implante de Prótese Vascular/efeitos adversos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Endoleak/diagnóstico por imagem , Endoleak/etiologiaRESUMO
The development of rapid and accurate assays is crucial to prevent the rapid spread of highly contagious respiratory infections such as coronavirus (COVID-19). Here, we developed a surface-enhanced Raman scattering (SERS)-enzyme-linked immunosorbent assay (ELISA) method that allows for the screening of multiple patient samples with high sensitivity on a 1536-well plate. As the well number on the ELISA well plate increases from 96 to 1536, the throughput of the assay increases but the sensitivity decreases due to the low number of biomarkers and the increase in non-specific binding species. To address this problem, silica (SiO2) beads were used to increase the surface-to-volume ratio and the loading density of biomarkers, thereby enhancing sensitivity. Using a three-dimensional gold nanoparticle (AuNP)@SiO2 SERS assay platform on a 1536-well plate, an immunoassay for the nucleocapsid protein biomarker of SARS-CoV-2 was performed and the limit of detection (LoD) decreased from 273 to 7.83 PFU/mL compared to using a two-dimensional assay platform with AuNPs. The proposed AuNPs@SiO2 SERS immunoassay (SERS-IA) platform is expected to dramatically decrease the false-negative diagnostic rate of the currently used lateral flow assay (LFA) or ELISA by enabling the positive diagnosis of patients with low virus concentrations.
RESUMO
BACKGROUND: The primary objective was to compare the accuracy of dynamic computed tomography (CT) angiography (d-CTA) with standardized triphasic contrast enhanced CT angiography (t-CTA) in diagnosing endoleak type after endovascular aortic repair (EVAR) using digital subtraction angiography (DSA) as reference standard. The secondary objective was to study the impact of d-CTA on image fusion-guided endoleak embolization. METHODS: A retrospective review of patients who underwent d-CTA imaging after EVAR between March 2019 and July 2021 was performed. Deidentified images were independently reviewed by two-two blinded readers to document endoleak type and target vessels. An impact of d-CTA-guided embolization was evaluated by a number of planning angiograms, radiation exposure, and accuracy of target vessel overlay. RESULTS: During the study period, 52 patients underwent d-CTA and 19 had all 3 modalities available for analysis. DSA imaging confirmed 4 (21.0%) type-I, 14 (73.7%) type-II, and 1 (5.3%) type-III endoleak. Findings from d-CTA matched with DSA in 19/19 cases (100%), whereas t-CTA matched in 14/19 cases (73.7%). In type-II endoleaks, the number of target vessels identified by d-CTA, t-CTA, and DSA were 23, 17, and 16, respectively. Mean dose-length product from d-CTA and t-CTA was 1,445 ± 551 and 1,612 ± 530 mGy × cm (P = 0.26). Nine patients underwent d-CTA-guided type-II endoleak embolization, using a median of 1 (range: 1-4) planning angiogram before embolization using 21.6 (± 8.7)% of total procedural radiation dose. Target vessel overlay was accurate in 9/9 (100%) cases. CONCLUSIONS: Dynamic, time-resolved CTA is more accurate compared to standardized triphasic contrast enhanced CTA in diagnosing endoleak type after EVAR. In type-II endoleak, d-CTA better identified target vessels and enabled safe, targeted embolization.