Simultaneous Heart-Kidney Transplant-Does Hospital Experience With Heart Transplant or Kidney Transplant Have a Greater Impact on Patient Outcomes?

High institutional transplant volume is associated with improved outcomes in isolated heart and kidney transplant. The aim of this study was to assess trends and outcomes of simultaneous heart-kidney transplant (SHKT) nationally, as well as the impact of institutional heart and kidney transplant volume on survival. All adult patients who underwent SHKT between 2005-2019 were identified using the United Network for Organ Sharing (UNOS) database. Annual institutional volumes in single organ transplant were determined. Univariate and multivariable analyses were conducted to assess the impact of demographics, comorbidities, and institutional transplant volumes on 1-year survival. 1564 SHKT were identified, increasing from 54 in 2005 to 221 in 2019. In centers performing SHKT, median annual heart transplant volume was 35.0 (IQR 24.0-56.0) and median annual kidney transplant volume was 166.0 (IQR 89.5-224.0). One-year survival was 88.4%. In multivariable analysis, increasing heart transplant volume, but not kidney transplant volume, was associated with improved 1-year survival. Increasing donor age, dialysis requirement, ischemic times, and bilirubin were also independently associated with reduced 1-year survival. Based on this data, high-volume heart transplant centers may be better equipped with managing SHKT patients than high-volume kidney transplant centers.

Contemporary national utilization of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest.

OBJECTIVE: The utilization of extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) has demonstrated promising evidence for the management of out-of-hospital cardiac arrest (OHCA). We aim to describe contemporary utilization and predictors of survival of patients receiving ECPR for OHCA. METHODS: The National Inpatient Sample (NIS) was queried to identify hospital discharge records of patients aged ≥18 years who underwent ECPR from 2012 to 2017. Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis of cardiac arrest, admitted urgently and placed on ECMO on Day 0 of hospitalization, were selected. Patients with a primary diagnosis indicative of veno-venous ECMO were excluded. Predictors of mortality were assessed using multivariable analyses. RESULTS: There were 1675 cases of ECPR, increasing from 185 cases in 2012 to 400 in 2017 (p < .001). Overall mortality was 63.3%, which remained stable over time (p = .441). Common diagnoses included ST-elevation myocardial infarction (39.1%), non-ST-elevation myocardial infarction (9.3%), and pulmonary embolism (13.7%). Percutaneous coronary intervention was performed in 495 patients (29.6%); coronary artery bypass grafting was performed in 125 patients (7.5%). In multivariable analysis, decreased age, female gender, and left ventricular (LV) decompression were associated with reduced mortality. CONCLUSION: Utilization of ECPR is increasing nationally with stable mortality rates. Younger age, female gender, and utilization of LV decompression were associated with increased survival.

Survival and readmission among patients with advanced cardiomyopathy undergoing transcatheter edge-to-edge mitral valve repair: Are we applying COAPT findings too broadly?

OBJECTIVE: Transcathether edge-to-edge mitral valve repair (TEER) has been shown to be an effective treatment for secondary mitral regurgitation (MR). However, the outcomes of TEER in patients with severe cardiomyopathy is less clear. The objective of this study is to determine the outcomes of such patients who underwent TEER at our institution. METHODS: A retrospective review of patients with severe cardiomyopathy, defined as ejection fraction ≤30% or the requirement of inotropic support preoperatively, undergoing TEER for secondary MR at our institution from 11/2016 to 11/2020 was performed. Univariate analysis associating preoperative characteristics with our primary endpoint of 1-year death or orthotopic heart transplant (OHT) was performed. Kaplan-Meier analysis was conducted for the composite outcome of death or OHT, as well as for heart failure-related readmission. Finally, an assessment of changes in MR severity from the preoperative, to immediate postoperative period, to 30-day postoperative period was conducted. RESULTS: There were 48 patients identified. Median age was 74.5 years (IQR 65.5-79.5), median ejection fraction was 21.5% (IQR 16.0-27.5), and 81.4% of patients had severe or torrential mitral regurgitation preoperatively. The composite endpoint of 1-year mortality or OHT occurred in 15 of 48 patients (31.3%, 14 deaths and 1 OHT). One-year heart failure readmission rate was 47.9%. Mortality or OHT at 2 years occurred in 45.8%. CONCLUSION: Patients at extremes of heart failure who underwent TEER had poor outcomes when assessed at 1-year. Our study may suggest that the results of cardiovascular outcomes assessment of the mitraclip percutaneous therapy for heart failure patients with secondary mitral regurgitation may not be applicable to patients with severe cardiomyopathy.

Partisanship, Policy, and Americans' Evaluations of State-Level COVID-19 Policies Prior to the 2020 Election.

The COVID-19 pandemic was a key policy issue during the 2020 election in the United States. As such, it is important to analyze how voters evaluated government responses to the pandemic. To this end, in this article, we examine factors that influenced Americans' evaluations of state-level COVID-19 policy responses. We find that during the pandemic onset period, Americans typically rated their state governments' responses more favorably if their governor was a co-partisan. In contrast, during the re-opening period, we find that Democrats relied on both partisanship and policy to evaluate their state-level responses, while Republicans continued to rely solely on partisanship. We contend that given the complex policy environment surrounding COVID-19, Americans may have not been fully aware of the policies their state governments adopted, so they relied on partisan cues to help them evaluate their state-level policy responses. But by the re-opening period, Americans likely had enough time to better understand state-level policy responses; this allowed Democrats to also evaluate their state-level responses based on policy. These findings shed light on how Americans evaluated COVID-19 responses just prior to the 2020 election.

Impacts of local public smoking bans on smoking behaviors and tobacco smoke exposure.

This paper examines the immediate and long-term effects of public smoking bans on smoking prevalence, smoking regularity, smoking intensity, and secondhand tobacco smoke exposure. We supplement the extensive literature on the effects of various types of tobacco control legislation on smoking behavior in developed countries by studying the provincial smoking bans and more recent national ban of a middle-income country, Argentina. We focus on the difference between full and partial smoking bans, and take advantage of the time and province variation in ban implementation in order to determine the causal effects of each type of ban. We find that full bans reduce national smoking prevalence over time, especially among younger demographic groups, but have no significant impact on intensity of smoking among smokers. Full bans also benefit nonsmokers, as they are associated with a significant reduction in environmental tobacco smoke exposure. Partial bans do not significantly impact smoking prevalence, and are found to increase smoking intensity among individuals who smoke every day. These findings provide support for ratification of full bans by all provinces according to the National Tobacco Control Law of 2011.

Racial and socioeconomic disparities in urgent transcatheter mitral valve repair: A National Inpatient Sample analysis.

BACKGROUND: Cardiac interventions performed urgently are known to be associated with poor outcomes compared with electively performed procedures. Transcatheter edge-to-edge mitral valve repair (TMVr) has developed as a reasonable alternative to mitral valve surgery in certain patient populations. We aimed to leverage a national database to identify predictors of urgent versus elective TMVr, as well as the association between urgency and outcomes. METHODS: The National Inpatient Sample (NIS) was queried to identify patients who underwent TMVr from 2016 to 2017. Hospitalizations were identified within the database as elective versus nonelective. Univariate and multivariable analyses were performed to identify patient characteristics associated with urgent procedures. In-hospital outcomes were assessed. RESULTS: There were 10,195 cases of TMVr in this cohort, 24.2% of which were performed urgently. In multivariable analysis, Hispanic race, Medicaid insurance, and low income were associated with increased likelihood of urgent hospital admission and TMVr. Additionally, small hospital size and Northeast region were associated with increased likelihood of urgent admission and procedure. Urgent TMVr was associated with increased mortality (4.5% vs. 1.6%, p < .001), prolonged length of stay (6.0 vs. 2.0, p < .001), and increased cost ($71,451.90 vs. $44,981.20, p < .001). CONCLUSIONS: Racial and socioeconomic disparities exist in the utilization of TMVr as an urgent versus elective procedure, suggesting differences in access to surveillance and preventive care. Urgent TMVr is associated with increased morbidity and mortality, prolonged length of stay, and increased hospital costs. Priority should be placed on mitigating such disparities to improve outcomes.

Accuracy of predicted effective orifice area in determining incidence of patient-prosthesis mismatch after transcatheter aortic valve replacement.

OBJECTIVE: Patient-prosthesis mismatch (PPM) is associated with poor outcomes after aortic valve replacement. The aim of this study was to assess the accuracy of indexed effective orifice area (EOAi) charts in predicting PPM after transcatheter aortic valve replacement (TAVR). METHODS: A retrospective review of 346 TAVR patients from January 2017 to November 2018 was performed. EOAi was predicted for patients based on published predictive tables using valve type, annulus diameter, and body surface area. Actual EOAi was calculated based on intraoperative transesophageal echocardiogram (TEE) measurements. PPM was defined by EOAi ≤ 0.85 cm2 /m2 . The accuracy of predicted PPM was assessed. Differences in clinical outcomes, including mean gradient, length of stay, mortality, complications, and change in Kansas City cardiomyopathy questionnaire score as an indicator of quality of life, were evaluated based on actual PPM. RESULTS: Of the 346 patients analyzed, 44 (12.7%) of patients had PPM on intraoperative TEE. Of the 182 patients who received Sapien 3 valves, 42 (23.1%) were predicted to have PPM while 25 (13.7%) had actual PPM. Of the 164 patients who received Evolut valves, 3 (1.8%) were predicted to have PPM while 19 (11.6%) had actual PPM. EOAi charts had poor sensitivity (40.0% for Sapien 3; 5.25% for Evolut) and positive predictive value (23.8% for Sapien 3; 33.3% for Evolut) for both valve types. CONCLUSION: Preoperative prediction of PPM in TAVR patients using tables of expected EOA demonstrates significant variation from actual PPM. The utility of EOAi charts to predict PPM in patients undergoing TAVR may be limited.

Impact of chronic lung disease on quality-of-life outcomes in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: As the symptoms for both chronic lung disease (CLD) and aortic stenosis (AS) frequently overlap, it may be challenging to determine the degree of symptomatic improvement expected for a patient with CLD after correction of AS. Our aim was to determine if patients with CLD have the same degree of quality-of-life improvement following transcatheter aortic valve replacement (TAVR) as patients without CLD. METHODS: A retrospective review of 238 TAVR patients from January 2017 to November 2018 who underwent preoperative pulmonary function tests and completed 30-day follow-up was performed. Patients were identified as having CLD with FEV1 more than 75% predicted. Postoperative outcomes and changes in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) were compared between groups. RESULTS: Of the 238 patients identified, 143 (60.0%) had CLD, 50 (35.0%) of whom had an obstructive disease pattern. Patients with CLD were more likely to be male, had higher rates of peripheral artery disease, and had lower baseline ejection fraction. There was no difference in STS Predicted Risk of Mortality, but patients with CLD were more likely to be designated as high-risk by surgeon evaluation. While initial and follow-up KCCQ-12 was lower for patients with CLD, there was no significant difference in degree of improvement (p = .900). When comparing patients with obstructive lung disease (FEV1/FVC < 0.70) to those without CLD, there was also no significant difference in the change of quality of life (p = .720). CONCLUSION: Although patients with concomitant severe AS and CLD have reduced baseline quality of life compared to patients without CLD, they experience a comparable degree of improvement following TAVR.

Evaluating the Validity of Risk Scoring in Predicting Pacemaker Rates following Transcatheter Aortic Valve Replacement.

INTRODUCTION: Requirement of permanent pacemaker (PPM) implantation is a known and common postoperative consequence of transcatheter aortic valve replacement (TAVR). The Emory risk score has been recently developed to help risk stratify the need for PPM insertion in patients undergoing TAVR with SAPIEN 3 valves. Our aim was to assess the validity of this risk score in our patient population, as well as its applicability to patients receiving self-expanding valves. METHODS: We conducted a retrospective review of 479 TAVR patients without preoperative pacemakers from November 2016 through December 2018. Preoperative risk factors included in the Emory risk score were collected for each patient: preoperative QRS, preoperative right bundle branch block (RBBB), preoperative syncope, and degree of valve oversizing. Multivariable analysis of the individual variables within the scoring system to identify predictors of PPM placement was performed. The predictive discrimination of the risk score for the risk of PPM placement after TAVR was assessed with the area under the receiver operating characteristic curve (AUC). RESULTS: Our results demonstrated that, of the 479 patients analyzed, 236 (49.3%) received balloon-expandable valves and 243 (50.7%) received self-expanding valves. Pacemaker rates were higher in patients receiving self-expanding valves than those receiving balloon-expandable valves (25.1% versus 16.1%, p=0.018). The Emory risk score showed a moderate correlation with pacemaker requirement in patients receiving each valve type, with AUC for balloon-expandable and self-expanding valves of 0.657 and 0.645, respectively. Of the four risk score components, preoperative RBBB was the only predictor of pacemaker requirement with an AUC of 0.615 for both balloon-expandable and self-expanding valves. Conclusion. In our cohort, the Emory risk score had modest predictive utility for PPM insertion after balloon-expandable and self-expanding TAVR. The risk score did not offer better discriminatory utility than that of preoperative RBBB alone. Understanding the determinants of PPM insertion after TAVR can better guide patient education and postoperative management.

Risk stratification for nonagenarians undergoing transcatheter aortic valve replacement.

BACKGROUND: There are disparate data on the outcomes of nonagenarians undergoing transcatheter aortic valve replacement (TAVR) compared with younger patients. The purpose of this study is to determine whether the Society of Thoracic Surgeons (STS) score can be used to identify the subset of nonagenarians that are at a significantly higher risk for poor postoperative outcomes after TAVR. METHODS: A total of 425 patients above the age of 80 underwent elective TAVR between 12/2013 and 2/2018 and were included in this study. Patients were deemed intermediate or high risk based on an STS predicted the risk of surgical mortality score of 3% to 8% and more than 8%, respectively. Differences in postoperative outcomes and/or 6-month mortality between intermediate and high-risk octogenarians and nonagenarians were compared. RESULTS: Of the 425 patients, 112 (26.4%) patients were nonagenarians, and 313 (73.6%) patients were octogenarians. Fifty-four (48.2%) of the nonagenarians were stratified as high-risk, while 78 (24.9%) of the octogenarians were stratified as high-risk. There were no statistically significant differences in the composite outcomes between intermediate-risk nonagenarians and intermediate-risk octogenarians. In contrast, high-risk nonagenarians were significantly more likely to experience the composite outcome of major perioperative complications and/or 6-month mortality as compared to high-risk octogenarians. CONCLUSION: Intermediate-risk nonagenarians undergoing TAVR have similar postoperative outcomes compared to intermediate-risk octogenarians. However, high-risk nonagenarian patients undergoing TAVR experience significantly poorer outcomes compared to their octogenarian counterparts. Judicious patient selection for TAVR in this subgroup of patients is therefore warranted.

COVID-19 Policy Response and the Rise of the Sub-National Governments.

We examine the roles of sub-national and national governments in Canada and the United States vis-à-vis the protective public health response in the onset phase of the global coronavirus disease 2019 (COVID-19) pandemic. This period was characterized in both countries by incomplete information as well as by uncertainty regarding which level of government should be responsible for which policies. The crisis represents an opportunity to study how national and sub-national governments respond to such policy challenges. In this article, we present a unique dataset that catalogues the policy responses of US states and Canadian provinces as well as those of the respective federal governments: the Protective Policy Index (PPI). We then compare the United States and Canada along several dimensions, including the absolute values of sub-national levels of the index relative to the total protections enjoyed by citizens, the relationship between early threat (as measured by the mortality rate near the start of the public health crisis) and the evolution of the PPI, and finally the institutional and legislative origins of the protective health policies. We find that the sub-national contribution to policy is more important for both the United States and Canada than are their national-level policies, and it is unrelated in scope to our early threat measure. We also show that the institutional origin of the policies as evidenced by the COVID-19 response differs greatly between the two countries and has implications for the evolution of federalism in each.

Nous examinons le rôle des gouvernements infranationaux et nationaux du Canada et des États-Unis dans l'adoption de mesures de protection de la santé publique au stade initial de la pandémie mondiale de COVID­19. Cette période a été caractérisée dans les deux pays par des informations incomplètes ainsi que par une incertitude quant à l'ordre de gouvernement responsable de telle ou telle politique. La crise offre l'occasion d'étudier comment les gouvernements nationaux et infranationaux relèvent ces défis politiques. Dans l'article qui suit, nous présentons un ensemble de données unique qui répertorie les décisions politiques des États américains et des provinces canadiennes en matière de protection, ainsi que celles des gouvernements fédéraux respectifs : l'indice de politique de protection (IPP). Nous comparons ensuite les États-Unis et le Canada selon plusieurs dimensions, notamment les valeurs absolues des niveaux infranationaux de l'IPP par rapport aux protections totales dont bénéficient les citoyens, la relation entre la « menace précoce ¼ (mesurée selon les taux de mortalité à l'approche du début de la crise de santé publique) et l'évolution de l'IPP et, enfin, les origines institutionnelles­législatives des politiques de protection de la santé. Nous constatons que la contribution infranationale à la politique est plus importante pour les deux pays mais qu'elle n'est pas liée à notre mesure de la « menace précoce ¼. Nous démontrons également que l'origine institutionnelle des politiques diffère grandement entre les deux pays et que cela a des répercussions sur l'évolution du fédéralisme.

Incidence of Acute Kidney Injury in Patients with Chronic Renal Insufficiency: Transcatheter versus Surgical Aortic Valve Replacement.

OBJECTIVES: The objective of this study is to determine incidence of acute kidney injury (AKI) associated with transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in patients with preexisting chronic kidney disease. BACKGROUND: The incidence of AKI in patients with preexisting renal insufficiency undergoing TAVR versus SAVR is not well described. METHODS: All patients with preexisting chronic kidney disease who underwent SAVR for aortic stenosis with or without concomitant coronary artery bypass grafting or TAVR from 5/2008 to 6/2017. Patients requiring preoperative hemodialysis were excluded. Chronic kidney disease was defined as an estimated glomerular filtrate rate (eGFR) of < 60 mL/min/1.73 m2. The incidence of postoperative AKI was compared using the RIFLE classification system for acute kidney injury. RESULTS: A total of 406 SAVR patients and 407 TAVR patients were included in this study. TAVR patients were older and had lower preoperative eGFR as compared to SAVR patients. Covariate adjustment using propensity score between the two groups showed that SAVR patients were more likely to have a more severe degree of postoperative AKI as compared to TAVR patients (OR = 4.75; 95% CI: 3.15, 7.17; p <.001). SAVR patients were more likely to require dialysis postoperatively as compared to TAVR patients (OR = 4.55; 95% CI: 1.29, 15.99; p <.018). CONCLUSION: In patients with preexisting chronic kidney disease, TAVR was associated with significantly less AKI as compared to SAVR.

Predictors of Increased Length of Hospital Stay in Patients with Severe Cardiomyopathy Undergoing Coronary Artery Bypass Grafting.

OBJECTIVE: Predictors of operative outcome in patients with severely depressed left ventricular ejection fraction (LVEF) undergoing coronary artery bypass grafting (CABG) remain poorly defined. This study aims to identify preoperative variables that are associated with increased postoperative length of hospital stay or operative mortality in this patient population. DESIGN: Retrospective study. SETTING: Single tertiary care university hospital. PARTICIPANTS: Patients undergoing isolated CABG between January 2012 and March 2017 with an LVEF ≤ 25%. INTERVENTIONS: Isolated CABG. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was a composite of prolonged length of stay, defined as postoperative length of stay >7 days or operative mortality. Of the 201 patients, 99 (49.3%) met the primary endpoint. Patient comorbidities, clinical presentation, presence of Q-waves on electrocardiogram, and echocardiographic parameters including ventricular dimensions and right heart dysfunction were not associated with the primary endpoint. On multivariable analysis, patients who were not on preoperative beta-blockers, patients with preoperative albumin of <3.5 g/dL, and higher Society of Thoracic Surgeons Predicted Risk of Mortality score were associated with increased prolonged length of stay or death. CONCLUSIONS: More than half of patients with severely depressed LVEF undergoing isolated CABG are able to be discharged within 7 days postoperatively. The absence of preoperative beta-blockers, low preoperative albumin levels, and higher Society of Thoracic Surgeons Predicted Risk of Mortality score are associated with more complicated or slower postoperative recovery after CABG in this patient population.

Impact of novel oral anticoagulants vs warfarin on effusions after coronary artery bypass grafting.

BACKGROUND: Novel oral anticoagulants (NOAC) have been shown to have comparable risk profiles compared with warfarin. However, data on the use of NOACs in cardiac surgery patients is limited. The aim of this study is to compare postoperative effusion rates in patients who were anticoagulated with NOACs vs warfarin after coronary artery bypass grafting (CABG). METHODS: A retrospective review of 2017 patients undergoing isolated CABG from 2014 to 2017 was performed. Of those patients, 246 patients (12.2%) were placed on either a NOAC or warfarin postoperatively. The combined rates of postoperative pericardial and pleural effusions requiring invasive intervention during the index hospitalization and up to 3 months postoperatively were compared between patients who were placed on NOACs vs warfarin. RESULTS: Of the 246 patients placed on oral anticoagulation after isolated CABG, 64 (26.0%) were placed on NOACs, and 182 (74.0%) received warfarin. There were no significant differences in preoperative coagulation profile and use of anticoagulation and antiplatelets preoperatively between the groups. Of the patients anticoagulated with NOACs postoperatively, 17 patients (26.6%) required invasive interventions for effusions compared with 24 patients (13.2%) in the cohort anticoagulated with warfarin (P < 0.014). Of the patients who required interventions for effusions, those on NOACs were more likely to require delayed interventions compared with those on warfarin. CONCLUSIONS: Patients receiving NOACs after CABG are at increased risk of developing effusions requiring invasive interventions compared to patients receiving warfarin. This increased risk should be taken into consideration when choosing the appropriate anticoagulation strategy for postoperative patients with CABG.

Pediatric thymectomy: a study of national trends in demographics, short-term outcomes, and cost.

BACKGROUND: Thymectomy in pediatric patients is an effective treatment for myasthenia gravis (MG), thymic neoplasms, and other rarer pathologies. It is an uncommon procedure in children and studies have focused on small, single-institution cohorts. We sought to better characterize its use by utilizing a national database. METHODS: The Kids' Inpatient Database was used to identify hospital discharge records of patients ≤ 20 years old who underwent thymectomy. A retrospective cross-sectional analysis for 2003, 2006, 2009, and 2012 was performed. Trends in patient characteristics, diagnosis, surgical approach, and short-term outcomes were analyzed. Risk factors were identified using univariate and multivariate analyses. RESULTS: There were 600 thymectomies identified. MG was the most common indication. Thoracoscopy is being used increasingly for all diagnoses except malignancy. The overall morbidity rate was 14.0%, with respiratory complications representing the largest group. No in-hospital deaths were identified. Private insurance was associated with shorter hospital stays and lower costs. Hispanic race was associated with more complications, longer stays, and higher costs. Thoracoscopic thymectomies had shorter stays than open procedures. CONCLUSION: Thymectomy in the pediatric population is being performed safely, with low morbidity and no identified mortalities. Thoracoscopy results in reduced length of stay and is being used increasingly. Of note, socioeconomic and racial factors impact outcomes.

Chemical and structural characterization of interstrand cross-links formed between abasic sites and adenine residues in duplex DNA.

A new type of interstrand DNA-DNA cross-link between abasic (Ap) sites and 2'-deoxyadenosine (dA) residues was recently reported, but the chemical structure and properties of this lesion were not rigorously established. Here we characterized the nucleoside cross-link remnant released by enzymatic digestion of duplex DNA containing the dA-Ap cross-link. A synthetic standard was prepared for the putative nucleoside cross-link remnant 6 in which the anomeric carbon of the 2-deoxyribose residue was connected to the exocyclic N(6)-amino group of dA. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that the synthetic material 6: matched the authentic cross-link remnant released by enzymatic digestion of cross-linked DNA. These findings establish the chemical structure of the dA-Ap cross-link released from duplex DNA and may provide methods for the detection of this lesion in cellular DNA. Both the nucleoside cross-link remnant 6: and the cross-link in duplex DNA were quite stable at pH 7 and 37°C, suggesting that the dA-Ap cross-link could be a persistent lesion with the potential to block the action of various DNA processing enzymes.

Effective molarity in a nucleic acid-controlled reaction.

Positioning of reactive functional groups within a DNA duplex can enable chemical reactions that otherwise would not occur to an appreciable extent. However, few studies have quantitatively defined the extent to which the enforced proximity of reaction partners in duplex DNA can favor chemical processes. Here, we measured substantial effective molarities (as high as 25M) afforded by duplex DNA to a reaction involving interstrand cross-link formation between 2'-deoxyadenosine and a 2-deoxyribose abasic (Ap) site.

Chemical structure and properties of interstrand cross-links formed by reaction of guanine residues with abasic sites in duplex DNA.

A new type of interstrand cross-link resulting from the reaction of a DNA abasic site with a guanine residue on the opposing strand of the double helix was recently identified, but the chemical connectivity of the cross-link was not rigorously established. The work described here was designed to characterize the chemical structure and properties of dG-AP cross-links generated in duplex DNA. The approach involved characterization of the nucleoside cross-link "remnant" released by enzymatic digestion of DNA duplexes containing the dG-AP cross-link. We first carried out a chemical synthesis and complete spectroscopic structure determination of the putative cross-link remnant 9b composed of a 2-deoxyribose adduct attached to the exocyclic N(2)-amino group of dG. A reduced analogue of the cross-link remnant was also prepared (11b). Liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis revealed that the retention times and mass spectral properties of synthetic standards 9b and 11b matched those of the authentic cross-link remnants released by enzymatic digestion of duplexes containing the native and reduced dG-AP cross-link, respectively. These results establish the chemical connectivity of the dG-AP cross-link released from duplex DNA and provide a foundation for detection of this lesion in biological samples. The dG-AP cross-link in duplex DNA was remarkably stable, decomposing with a half-life of 22 days at pH 7 and 23 °C. The intrinsic chemical stability of the dG-AP cross-link suggests that this lesion in duplex DNA may have the power to block DNA-processing enzymes involved in transcription and replication.

Inactivation of protein tyrosine phosphatases by dietary isothiocyanates.

Isothiocyanates are bioactive dietary phytochemicals that react readily with protein thiol groups. We find that isothiocyanates are time-dependent inactivators of cysteine-dependent protein tyrosine phosphatases (PTPs). Rate constants for the inactivation of PTP1B and SHP-2 by allyl isothiocyanate and sulforaphane range from 2 to 16 M(-1)s(-1). Results in the context of PTP1B are consistent with a mechanism involving covalent, yet reversible, modification of the enzyme's active site cysteine residue.

Applying the theory of planned behavior to predict COVID-19 booster vaccination intentions of college students.

Objective: The purpose of this study was: (a) to determine COVID-19 vaccination rates among college students, (b) to assess what proportion of college students self-report currently or previously having COVID-19, and (c) to test theory of planned behavior (TPB)-based constructs in predicting the COVID-19 booster vaccination behavioral intentions. Methods: A non-experimental, cross-sectional study design was applied. Participants: The sample consisted of 288 college students ages 18 years and older. Results: The stepwise multiple regression revealed that attitude (ß = .329; p < .001) and subjective norm (ß = .244; p < .001) were statistically significant predictors of intention to receive the COVID-19 booster, accounting for 86.7% (Adjusted R2 = .867, F (2, 204 = 673.002, p < .001) of the variance. Conclusions: College students are at high risk for more severe complications of COVID-19 infection due to low vaccination rates. The instrument designed for this study may be used to design TPB-based interventions to increase COVID-19 vaccination and booster intentions of college students.