Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

Association between Medicaid expansion status and lung cancer screening exam growth: findings from the ACR lung cancer registry.

PURPOSE: To determine if Medicaid expansion is associated with increased volumes of lung cancer screenings. METHODS: A quasi-experimental study was performed to compare the annual growth rates in lung cancer screenings between states that expanded Medicaid (n = 31) versus those that did not (n = 17). Using the American College of Radiology Lung Cancer Screening Registry, we calculated the average annual growth rate between 2016 and 2019 for both groups. Secondary analyses between these two groups also included calculations of the percentages of studies considered appropriate by USPSTF criteria. RESULTS: No significant difference was identified in the average annual growth in lung cancer screenings between Medicaid expanding and non-expanding states (57.6%, 50.3%, P = 0.51). No difference was observed in the percentage of studies considered appropriate (Medicaid expanding = 89.6%, non-expanding = 90.2%, P = 0.72). At baseline, there were socioeconomic differences between both groups of states. Medicaid expanding states had a more urban population (76.5% versus 67.9%, P = 0.05) and higher average incomes ($56,947,$49,876, P \u3c 0.05). CONCLUSION: No association is found between Medicaid expansion and increasing volumes of lung cancer screening exams. Although no data is available in the registry for screening exams before the implementation of Medicaid expansion (2014), most nationwide estimates of lung screening rates report a low baseline (\u3c5%). Furthermore, despite being advantaged in other ways, such as with a more urban population or with higher incomes, the Medicaid expansion cohort does not demonstrate a higher growth rate. These findings suggest Medicaid expansion alone will not increase lung cancer screenings

Transcriptional responses of Arabidopsis thaliana plants to As (V) stress

Background Arsenic is toxic to plants and a common environmental pollutant. There is a strong chemical similarity between arsenate [As (V)] and phosphate (Pi). Whole genome oligonucleotide microarrays were employed to investigate the transcriptional responses of Arabidopsis thaliana plants to As (V) stress. Results Antioxidant-related genes (i.e. coding for superoxide dismutases and peroxidases) play prominent roles in response to arsenate. The microarray experiment revealed induction of chloroplast Cu/Zn superoxide dismutase (SOD) (at2g28190), Cu/Zn SOD (at1g08830), as well as an SOD copper chaperone (at1g12520). On the other hand, Fe SODs were strongly repressed in response to As (V) stress. Non-parametric rank product statistics were used to detect differentially expressed genes. Arsenate stress resulted in the repression of numerous genes known to be induced by phosphate starvation. These observations were confirmed with qRT-PCR and SOD activity assays. Conclusion Microarray data suggest that As (V) induces genes involved in response to oxidative stress and represses transcription of genes induced by phosphate starvation. This study implicates As (V) as a phosphate mimic in the cell by repressing genes normally induced when available phosphate is scarce. Most importantly, these data reveal that arsenate stress affects the expression of several genes with little or unknown biological functions, thereby providing new putative gene targets for future research

The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer

We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH proteins, called hMSH2. Expression of hMSH2 in E. coli causes a dominant mutator phenotype, suggesting that hMSH2, like other divergent MutS homologs, interferes with the normal bacterial mismatch repair pathway. hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC). A T to C transition mutation has been detected in the -6 position of a splice acceptor site in sporadic colon tumors and in affected individuals of two small HNPCC kindreds. These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene

Sensitivity of a real-time PCR method for the detection of transgenes in a mixture of transgenic and non-transgenic seeds of papaya (\u3cem\u3eCarica papaya\u3c/em\u3e L.)

Background Genetically engineered (GE) ringspot virus-resistant papaya cultivars ‘Rainbow’ and ‘SunUp’ have been grown in Hawai’i for over 10 years. In Hawai’i, the introduction of GE papayas into regions where non-GE cultivars are grown and where feral non-GE papayas exist have been accompanied with concerns associated with transgene flow. Of particular concern is the possibility of transgenic seeds being found in non-GE papaya fruits via cross-pollination. Development of high-throughput methods to reliably detect the adventitious presence of such transgenic material would benefit both the scientific and regulatory communities. Results We assessed the accuracy of using conventional qualitative polymerase chain reaction (PCR) as well as real-time PCR-based assays to quantify the presence of transgenic DNA from bulk samples of non-GE papaya seeds. In this study, an optimized method of extracting high quality DNA from dry seeds of papaya was standardized. A reliable, sensitive real-time PCR method for detecting and quantifying viral coat protein (cp) transgenes in bulk seed samples utilizing the endogenous papain gene is presented. Quantification range was from 0.01 to 100 ng/μl of GE-papaya DNA template with a detection limit as low as 0.01% (10 pg). To test this system, we simulated transgene flow using known quantities of GE and non-GE DNA and determined that 0.038% (38 pg) GE papaya DNA could be detected using real-time PCR. We also validated this system by extracting DNA from known ratios of GE seeds to non-GE seeds of papaya followed by real-time PCR detection and observed a reliable detection limit of 0.4%. Conclusions This method for the quick and sensitive detection of transgenes in bulked papaya seed lots using conventional as well as real-time PCR-based methods will benefit numerous stakeholders. In particular, this method could be utilized to screen selected fruits from maternal non-GE papaya trees in Hawai’i for the presence of transgenic seed at typical regulatory threshold levels. Incorporation of subtle differences in primers and probes for variations in cp worldwide should allow this method to be utilized elsewhere when and if deregulation of transgenic papaya occurs

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

Background Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased and Aims blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Methods Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. Results A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. Conclusions This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.BACKGROUND AND AIMS: Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. METHODS: Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non-sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. RESULTS: A total of 460 980 and 14 462 patients were identified for the non-sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference -0.04 mmHg (95% confidence interval -0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. CONCLUSIONS: This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice

Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret

Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge