Effect of oxidative stress on ABC transporters: contribution to epilepsy pharmacoresistance

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response

Early critical care course in children after liver transplant

Objective. To review the critical care course of children receiving orthotopic liver transplantation (OLT)

Global text mining and development of pharmacogenomic knowledge resource for precision medicine

Understanding patients' genomic variations and their effect in protecting or predisposing them to drug response phenotypes is important for providing personalized healthcare. Several studies have manually curated such genotype-phenotype relationships into organized databases from clinical trial data or published literature. However, there are no text mining tools available to extract high-accuracy information from such existing knowledge. In this work, we used a semiautomated text mining approach to retrieve a complete pharmacogenomic (PGx) resource integrating disease-drug-gene-polymorphism relationships to derive a global perspective for ease in therapeutic approaches. We used an R package, pubmed.mineR, to automatically retrieve PGx-related literature. We identified 1,753 disease types, and 666 drugs, associated with 4,132 genes and 33,942 polymorphisms collated from 180,088 publications. With further manual curation, we obtained a total of 2,304 PGx relationships. We evaluated our approach by performance (precision = 0.806) with benchmark datasets like Pharmacogenomic Knowledgebase (PharmGKB) (0.904), Online Mendelian Inheritance in Man (OMIM) (0.600), and The Comparative Toxicogenomics Database (CTD) (0.729). We validated our study by comparing our results with 362 commercially used the US- Food and drug administration (FDA)-approved drug labeling biomarkers. Of the 2,304 PGx relationships identified, 127 belonged to the FDA list of 362 approved pharmacogenomic markers, indicating that our semiautomated text mining approach may reveal significant PGx information with markers for drug response prediction. In addition, it is a scalable and state-of-art approach in curation for PGx clinical utility

Genetic landscape of common epilepsies: advancing towards precision in treatment

Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood absence epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy and epilepsy with generalized tonic-clonic seizure on awakening and focal epilepsy like temporal lobe epilepsy and cryptogenic focal epilepsy. In 70% of the epilepsy cases, genetic factors are responsible either as single genetic variant in rare epilepsies or multiple genetic variants acting along with different environmental factors as in common epilepsies. Genetic testing and precision treatment have been developed for a few rare epilepsies and is lacking for common epilepsies due to their complex nature of inheritance. Precision medicine for common epilepsies require a panoramic approach that incorporates polygenic background and other non-genetic factors like microbiome, diet, age at disease onset, optimal time for treatment and other lifestyle factors which influence seizure threshold. This review aims to comprehensively present a state-of-art review of all the genes and their genetic variants that are associated with all common epilepsy subtypes. It also encompasses the basis of these genes in the epileptogenesis. Here, we discussed the current status of the common epilepsy genetics and address the clinical application so far on evidence-based markers in prognosis, diagnosis, and treatment management. In addition, we assessed the diagnostic predictability of a few genetic markers used for disease risk prediction in individuals. A combination of deeper endo-phenotyping including pharmaco-response data, electro-clinical imaging, and other clinical measurements along with genetics may be used to diagnose common epilepsies and this marks a step ahead in precision medicine in common epilepsies management

The association of care burden with motivation of vaccine acceptance among caregivers of stroke patients during the COVID-19 pandemic: mediating roles of problematic social media use, worry, and fear

Background: The aim of the present study was to investigate the relationship between care burden and motivation of COVID-19 vaccine acceptance among caregivers of patients who have experienced a stroke and to explore the mediating roles of social media use, fear of COVID-19, and worries about infection in this relationship. Methods: A cross-sectional survey study with 172 caregivers of patients who had experienced a stroke took part in a Taiwan community hospital. All participants completed the Zarit Burden Interview, Bergen Social Media Addiction Scale, Worry of Infection Scale, Fear of COVID-19 Scale, and Motors of COVID-19 Vaccine Acceptance Scale. Multiple linear regression model was applied to construct and explain the association among the variables. Hayes Process Macro (Models 4 and 6) was used to explain the mediation effects. Results: The proposed model significantly explained the direct association of care burden with motivation of COVID-19 vaccine acceptance. Despite the increased care burden associated with decreased vaccine acceptance, problematic social media use positively mediated this association. Moreover, problematic social media use had sequential mediating effects together with worry of infection or fear of COVID-19 in the association between care burden and motivation of vaccine acceptance. Care burden was associated with motivation of vaccine acceptance through problematic social media use followed by worry of infection. Conclusions: Increased care burden among caregivers of patients who have experienced a stroke may lead to lower COVID-19 vaccines acceptance. Moreover, problematic social media use was positively associated with their motivation to get COVID-19 vaccinated. Therefore, health experts and practitioners should actively disseminate accurate and trustworthy factual information regarding COVID-19, while taking care of the psychological problems among caregiv-ers of patients who have experienced a stroke

Fear, stress, susceptibility, and problematic social media use explain motivation for COVID-19 preventive behaviors among patients with stroke and their caregivers

The COVID-19 pandemic presented significant challenges for individuals who experienced stroke and their caregivers. It is essential to understand the factors affecting preventive behavior in these populations. Therefore, the present study examined the factors that influenced COVID-19 preventive behavior and motivation for COVID-19 vaccine uptake among patients with stroke and their caregivers. A cross-sectional study comprising 191 participants (81 patients with stroke and 110 caregivers) was carried out. Participants completed a survey assessing fear of COVID-19, stress, perceived susceptibility, problematic social media use, preventive behaviors, and motivation for vaccine uptake. Statistical analyses included descriptive statistics, Pearson correlations, and multiple linear regressions. Motivation for COVID-19 vaccine uptake was significantly positively correlated with problematic social media use (r = 0.225, P = .002), perceived susceptibility (r = 0.197, P = .008), and fear of COVID-19 (r = 0.179, P = .015), but negatively correlated with stress (r = −0.189, P = .010). Caregivers, compared to patients, showed a lower level of preventive behavior (standardized coefficient = −0.23, P = .017). Furthermore, higher levels of fear were associated with increased preventive behavior (standardized coefficient = 0.22, P = .006), while greater stress correlated with lower preventive behavior (standardized coefficient = −0.38, P < .001). Among patients with stroke and their caregivers, motivation of COVID-19 vaccine uptake and preventive behaviors were influenced by factors such as fear, perceived susceptibility, social media use, and stress. By using strategies such as targeted education, support, and communication campaigns, healthcare providers and policymakers may be able to enhance the well-being of patients with stroke and their caregivers during future pandemics. What do we already know about this topic? Preventive behaviors and vaccine uptake are important factors for people not to be infected by the COVID-19. How does your research contribute to the field? The present study offers significant contributions to the field by enhancing understanding of preventive behaviors during crises, specifically for patients with stroke and their caregivers. It highlights the importance of a number of factors including fear, stress, and perceived susceptibility in influencing vaccine uptake and preventive behaviors. These insights are crucial for developing targeted interventions and effective communication strategies, especially in managing psychological stressors. What are your research's implications toward theory, practice, or policy? Strategies to reduce stress and provide coping mechanisms for patients with stroke and caregivers of patients with stroke may enhance their ability to engage in preventive behaviors; additionally, healthcare providers should actively address and debunk misinformation on social media platforms to promote accurate and evidence-based information. Original Researc

Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12

PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life

Post-traumatic stress disorder in Chinese teachers during COVID-19 pandemic: roles of fear of COVID-19, nomophobia, and psychological distress

There are limited data concerning the prevalence of post-traumatic stress disorder (PTSD) among teachers. Therefore, the present study estimated the prevalence of PTSD among mainland Chinese teachers during the COVID-19 pandemic and to construct a model with mediation and moderation effects to explain the PTSD. Data collection was conducted in schools in the Jiangxi province between October and November 2020 among k-12 schoolteachers. An online survey, including five different psychometric scales, was used to collect data. All participants were assessed for PTSD using the Chinese version of the PTSD Checklist for DSM-5 (PCL-5). Hayes’ PROCESS Model 8 was used to examine the potential factors explaining a higher PTSD scores. A total of 2603 teachers from k-12 schools participated. With the cutoff score at 31, the prevalence of PTSD was 12.3% but decreased to 1.0% when the cutoff score was at 49. Nomophobia moderated the effects of Fear of COVID-19 Scale on PTSD. The findings suggest that fear of COVID-19 among teachers leads to PTSD via psychological distress, highlighting the moderating effect of nomophobia in this association. Based on the study’s findings, psychological interventions and educational training are needed to reduce fear among teachers at higher risk of developing PTSD

To retain or remove the syndesmotic screw: a review of literature

Introduction: Syndesmotic positioning screws are frequently placed in unstable ankle fractures. Many facets of adequate placement techniques have been the subject of various studies. Whether or not the syndesmosis screw should be removed prior to weight-bearing is still debated. In this study, the recent literature is reviewed concerning the need for removal of the syndesmotic screw. Materials and methods: A comprehensive literature search was conducted in the electronic databases of the Cochrane Library, Pubmed Medline and EMbase from January 2000 to October 2010. Results: A total of seven studies were identified in the literature. Most studies found no difference in outcome between retained or removed screws. Patients with screws that were broken, or showed loosening, had similar or improved outcome compared to patients with removed screws. Removal of the syndesmotic screws, when deemed necessary, is usually not performed before 8-12 weeks. Conclusion: There is paucity in randomized controlled trials on the absolute need for removal of the syndesmotic screw. However, current literature suggests that it might be reserved for intact screws that cause hardware irritation or reduced range of motion after 4-6 months

Sub-arcsecond imaging with the International LOFAR Telescope I. Foundational calibration strategy and pipeline

The International LOFAR Telescope is an interferometer with stations spread across Europe. With baselines of up to ~2000 km, LOFAR has the unique capability of achieving sub-arcsecond resolution at frequencies below 200 MHz. However, it is technically and logistically challenging to process LOFAR data at this resolution. To date only a handful of publications have exploited this capability. Here we present a calibration strategy that builds on previous high-resolution work with LOFAR. It is implemented in a pipeline using mostly dedicated LOFAR software tools and the same processing framework as the LOFAR Two-metre Sky Survey (LoTSS). We give an overview of the calibration strategy and discuss the special challenges inherent to enacting high-resolution imaging with LOFAR, and describe the pipeline, which is publicly available, in detail. We demonstrate the calibration strategy by using the pipeline on P205+55, a typical LoTSS pointing with an 8 h observation and 13 international stations. We perform in-field delay calibration, solution referencing to other calibrators in the field, self-calibration of these calibrators, and imaging of example directions of interest in the field. We find that for this specific field and these ionospheric conditions, dispersive delay solutions can be transferred between calibrators up to ~1.5° away, while phase solution transferral works well over ~1°. We also demonstrate a check of the astrometry and flux density scale with the in-field delay calibrator source. Imaging in 17 directions, we find the restoring beam is typically ~0.3′′ ×0.2′′ although this varies slightly over the entire 5 deg2 field of view. We find we can achieve ~80–300 μJy bm−1 image rms noise, which is dependent on the distance from the phase centre; typical values are ~90 μJy bm−1 for the 8 h observation with 48 MHz of bandwidth. Seventy percent of processed sources are detected, and from this we estimate that we should be able to image roughly 900 sources per LoTSS pointing. This equates to ~ 3 million sources in the northern sky, which LoTSS will entirely cover in the next several years. Future optimisation of the calibration strategy for efficient post-processing of LoTSS at high resolution makes this estimate a lower limit