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Single-nucleotide polymorphisms in ETS1 are associated with systemic lupus erythematosus (SLE). Ets1-/- mice develop SLE-like symptoms, suggesting that dysregulation of this transcription factor is important to the onset or progression of SLE. We used conditional deletion approaches to examine the impact of Ets1 expression in different immune cell types. Ets1 deletion on CD4+ T cells, but not B cells or dendritic cells, resulted in the SLE autoimmunity, and this was associated with the spontaneous expansion of T follicular helper type 2 (Tfh2) cells. Ets1-/- Tfh2 cells exhibited increased expression of GATA-3 and interleukin-4 (IL-4), which induced IgE isotype switching in B cells. Neutralization of IL-4 reduced Tfh2 cell frequencies and ameliorated disease parameters. Mechanistically, Ets1 suppressed signature Tfh and Th2 cell genes, including Cxcr5, Bcl6, and Il4ra, thus curbing the terminal Tfh2 cell differentiation process. Tfh2 cell frequencies in SLE patients correlated with disease parameters, providing evidence for the relevance of these findings to human disease.
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Diferenciación Celular/inmunología , Lupus Eritematoso Sistémico/inmunología , Proteína Proto-Oncogénica c-ets-1/inmunología , Células Th2/inmunología , Animales , Autoinmunidad/genética , Autoinmunidad/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Expresión Génica/inmunología , Perfilación de la Expresión Génica , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteína Proto-Oncogénica c-ets-1/genética , Proteína Proto-Oncogénica c-ets-1/metabolismo , Células Th2/metabolismoRESUMEN
Anthracyclines, topoisomerase II enzyme poisons that cause DNA damage, are the mainstay of acute myeloid leukemia (AML) treatment. However, acquired resistance to anthracyclines leads to relapse, which currently lacks effective treatment and is the cause of poor survival in individuals with AML. Therefore, the identification of the mechanisms underlying anthracycline resistance remains an unmet clinical need. Here, using patient-derived primary cultures and clinically relevant cellular models that recapitulate acquired anthracycline resistance in AML, we have found that GCN5 (also known as KAT2A) mediates transcriptional upregulation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in AML relapse, independently of the DNA-damage response. We demonstrate that anthracyclines fail to induce DNA damage in resistant cells, owing to the loss of expression of their target enzyme, TOP2B; this was caused by DNA-PKcs directly binding to its promoter upstream region as a transcriptional repressor. Importantly, DNA-PKcs kinase activity inhibition re-sensitized AML relapse primary cultures and cells resistant to mitoxantrone, and abrogated their tumorigenic potential in a xenograft mouse model. Taken together, our findings identify a GCN5-DNA-PKcs-TOP2B transcriptional regulatory axis as the mechanism underlying anthracycline resistance, and demonstrate the therapeutic potential of DNA-PKcs inhibition to re-sensitize resistant AML relapse cells to anthracycline.
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Proteína Quinasa Activada por ADN , Leucemia Mieloide Aguda , Humanos , Ratones , Animales , Proteína Quinasa Activada por ADN/genética , Proteína Quinasa Activada por ADN/metabolismo , Resistencia a Antineoplásicos/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , ADN-Topoisomerasas de Tipo II/uso terapéutico , Antraciclinas/farmacología , Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos , Recurrencia , ADN , Proteínas de Unión a Poli-ADP-RibosaRESUMEN
Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing a formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: ß-amyloid (Aß) and tau protein. While the amyloid cascade theory has long dominated AD research, recent developments have ignited debates about its centrality. Aß plaques and tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal antibodies targeting Aß, have been approved, albeit amidst controversy, raising questions about the therapeutic efficacy of Aß-focused interventions. On the other hand, tau, specifically its hyperphosphorylation, disrupts microtubule stability and contributes to neuronal dysfunction. Various post-translational modifications of tau drive its aggregation into NFTs. Emerging treatments targeting tau, such as GSK-3ß and CDK5 inhibitors, have shown promise in preclinical and clinical studies. Restoring the equilibrium between protein kinases and phosphatases, notably protein phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily regulated by its phosphorylation state. Activation of tau-specific phosphatases offers potential for mitigating tau pathology. The evolving landscape of AD drug development emphasizes tau-centric therapies and reevaluation of the amyloid cascade hypothesis. Additionally, exploring the role of neuroinflammation and its interaction with tau pathology present promising research directions.
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Enfermedad de Alzheimer , Proteínas tau , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/terapia , Proteínas tau/metabolismo , Fosforilación , Animales , Péptidos beta-Amiloides/metabolismoRESUMEN
OBJECTIVE: There is a dearth of literature describing young adult (YA) cancer survivors' experiences with cancer-related cognitive impairment (CRCI). We aimed to elucidate CRCI among YA cancer survivors and identify potentially modifiable risk factors. METHODS: We conducted individual qualitative interviews with YA cancer survivors aged 18-30 years at study enrollment and used applied thematic analysis to identify themes across three topics (i.e., affected cognitive abilities, risk and protective factors influencing the impact of CRCI, and strategies for coping with CRCI). RESULTS: YA cancer survivors (N = 20) were, on average, 23 years old at diagnosis and 26 years old when interviewed. Diverse cancer types and treatments were represented; most participants (85%) had completed cancer treatment. Participants described experiences across three qualitative topics: (1) affected cognitive abilities (i.e., concentration and attention, prospective memory, and long-term memory), (2) Risk factors (i.e., fatigue, sleep problems, mood, stress/distractions, and social isolation) and protective factors (i.e., social support), and (3) coping strategies, including practical strategies that helped build self-efficacy (e.g., writing things down, reducing distractions), beneficial emotion-focused coping strategies (e.g., focus on health, faith/religion), strategies with mixed effects (i.e., apps/games, medications/supplements, and yoga), and "powering through" strategies that exacerbated stress. CONCLUSIONS: YA cancer survivors experience enduring cognitive difficulties after treatment. Specific concerns highlight the importance of attention and executive functioning impairments, long-term memory recall, and sensitivity to distractions. Future work is needed to improve assessment and treatment of CRCI among YA cancer survivors.
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Supervivientes de Cáncer , Disfunción Cognitiva , Neoplasias , Humanos , Adulto Joven , Adulto , Supervivientes de Cáncer/psicología , Cognición , Disfunción Cognitiva/etiología , Neoplasias/psicología , EncéfaloRESUMEN
AIM: Pharmacists are essential members of hospital antimicrobial stewardship (AMS) teams. A lack of self-perceived confidence can limit pharmacists' involvement and contributions. Pharmacists working in AMS have reported a lack of confidence. There is currently a lack of validated measures to assess pharmacists' self-perceived confidence when working in AMS and contributors to this confidence. This study aimed to identify variables contributing to pharmacist self-perceived confidence and validate an AMS hospital pharmacist survey tool using confirmatory factor analysis (CFA). METHODS: Responses from a survey of Australian and French hospital pharmacists were used to undertake CFA and path analysis on factors related to pharmacists' self-perceived confidence. It was hypothesized that pharmacists' self-perceived confidence would be impacted by time working in AMS, perceived importance of AMS programmes, perceived barriers to participating in AMS and current participation. RESULTS: CFA demonstrated a good model fit between the factors. Items included in the model loaded well to their respective factors with acceptable reliability. Path analysis demonstrated that time working in AMS had a significant impact on pharmacists' self-perceived confidence, while perceived barriers had a negatively significant relationship. Pharmacy participation in AMS and perceived importance of AMS programmes had a non-significant impact. CONCLUSION: Findings demonstrated that the survey tool showed good validity and identified factors that can impact pharmacists' self-perceived confidence when working in hospital AMS programmes. Having a validated survey tool can identify factors that can reduce pharmacists' self-perceived confidence. Strategies can then be developed to address these factors and subsequently improve pharmacists' self-perceived confidence.
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Programas de Optimización del Uso de los Antimicrobianos , Actitud del Personal de Salud , Farmacéuticos , Servicio de Farmacia en Hospital , Humanos , Farmacéuticos/psicología , Análisis Factorial , Encuestas y Cuestionarios , Femenino , Masculino , Australia , Servicio de Farmacia en Hospital/organización & administración , Autoimagen , Rol Profesional , Francia , Adulto , Reproducibilidad de los Resultados , Persona de Mediana EdadRESUMEN
Breast cancer is one of the most basilisk cancers for women due to its high mortality rate which can be prevented drastically with early-stage detection. In this work, the adsorption mechanism of two volatile organic compounds that are present in the breath of breast cancer patients, 2-Methyloctane and 3, 3-Dimethylpentane, has been investigated on aluminum phosphide nanotubes (AlPNT) and gallium phosphide nanotubes (GaPNT) in order to understand their feasibility as sensor materials to diagnosis breast cancer at early stage. We have used the quantum mechanical approach by employing density functional theory using B3LYP-D3 hybrid potential for noncovalent interaction along with the LanL2DZ basis in the Gaussian 09 software package. The adsorption properties analyses suggest that GaPNT exhibits better sensing behavior as well as proclaims 12.6% greater adsorption energy for 2-Methyloctane and 9.4% greater adsorption energy for 3, 3-Dimethylpentane than AlPNT. Other structural and electric properties analyses satisfy this conclusion and suggest that GaPNT exhibits higher stability than AlPNT and could possibly be a potential candidate for developing biosensors to detect breast cancer at the preliminary stages.
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Neoplasias de la Mama , Teoría Funcional de la Densidad , Nanotubos , Fosfinas , Neoplasias de la Mama/diagnóstico , Humanos , Femenino , Nanotubos/química , Fosfinas/química , Adsorción , Galio/química , Octanos/química , Compuestos Orgánicos Volátiles/análisis , Técnicas Biosensibles/métodosRESUMEN
OBJECTIVE: Through predictable pharmacokinetics-including a convenient fixed-dose regimen, direct oral anticoagulants (DOACs) are preferred over previous treatments in anticoagulation for various indications. However, the association between higher body weight and the risk of adverse consequences is not well studied among DOAC users. We aim to explore the association of body weight and adverse clinical outcomes in DOAC users. METHODS: A total of 97,413 anonymised DOAC users in a tertiary care setting were identified following structured queries on the electronic health records (EHRs) to extract the feature-rich anonymised dataset. The prepared dataset was analysed, and the features identified with machine learning (ML) informed the adjustments of covariates in the multivariate regression analysis to examine the association. Kaplan-Meier analysis was performed to evaluate the mortality benefits of DOACs. RESULTS: Among DOAC users, the odds of adverse clinical outcomes, such as clinically relevant non-major bleeding (CRNMB), ischaemic stroke, all-cause mortality, and prolonged hospital stay, were lower in patients with overweight, obesity, or morbid obesity than in patients with normal body weight. The odds of ischaemic stroke (OR 0.42, 95% CI: 0.36-0.88, p = 0.001) and all-cause mortality (OR 0.87, 95% CI: 0.81-0.95, p = 0.001) were lower in patients with morbid obesity than in patients with normal body weight. In the Kaplan-Meier analysis, apixaban was associated with a significantly lower rate of mortality overall and in obesity and overweight subgroups than other DOACs (p < 0.001). However, rivaroxaban performed better than apixaban in the morbid obesity subgroup (p < 0.001). CONCLUSION: This study shows the positive effects of DOAC therapy on clinical outcomes, particularly in patients with high body weight. However, this still needs validation by further studies particularly among patients with morbid obesity.
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Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Obesidad Mórbida , Accidente Cerebrovascular , Humanos , Warfarina , Isquemia Encefálica/tratamiento farmacológico , Obesidad Mórbida/complicaciones , Obesidad Mórbida/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Dabigatrán/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Estudios Retrospectivos , Anticoagulantes/efectos adversos , Rivaroxabán/uso terapéutico , Hospitales , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Administración OralRESUMEN
INTRODUCTION: Vitamin D, known for its role in bone health, is now being explored for its immunomodulatory effects. This study aimed to evaluate the impact of vitamin D supplementation on mortality in coronavirus disease 2019 (COVID-19) patients through a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and preprint servers for eligible trials up to July 8, 2024. Two investigators independently screened the records and assessed the risk of bias using the Cochrane Risk of Bias Tool. Trials were eligible if they compared vitamin D with control interventions in adults with COVID-19. Data extraction and analysis were carried out independently, employing a random-effects model to estimate pooled odds ratios for mortality. RESULTS: Nineteen randomized controlled trials with 2495 participants were included. The meta-analysis showed a significant reduction in all-cause mortality with vitamin D supplementation (pooled OR 0.72, 95% CI 0.53-0.98; I2 = 20%). Subgroup analysis for severe COVID-19 cases also indicated significant mortality reduction (pooled OR 0.57, 95% CI 0.35-0.92; I2 = 18%). CONCLUSION: Vitamin D supplementation appears to reduce mortality in COVID-19 patients, especially in severe cases. These findings highlight the potential benefits of vitamin D as an adjunct treatment in COVID-19, though further large-scale trials are needed to confirm these effects and determine optimal dosing.
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Migraine is one of the common neurological disease affecting around 23% of the Pakistani population. Prompt treatment is required to regain the functional ability of patients. The present study was designed to develop sumatriptan succinate orodispersible tablets that would quickly overcome acute migraine episodes using 22 full-factorial design. The chitosan and sodium starch glycolate were taken as independent variables; friability, disintegration, dispersion time and water absorption ratio as response variables. Eight trial formulations were generated by Design Expert® software. The main effect plots were used to check the interaction of formulations with response variables. All trial formulations showed good micromeritic properties in terms of angle of repose (19.59o-24.57°), Carr's index (17.08-24.90%) and Hausner's ratio (1.20-1.33). The tablets wetted quickly (17.1- 39 sec) in dispersion medium, showed higher water absorption ratio (188-341 sec) and disintegrated quickly (13-20 sec) with an excellent dissolution rate (94-99%). The main effect plots show interactions between the independent variables against most of the study responses. A 22 full-factorial model was found to be effective in studying the influence of formulation variables on response parameters. Both chitosan and sodium starch glycolate can be used in combination to fabricate an effective orodispersible formulation of sumatriptan succinate.
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Quitosano , Trastornos Migrañosos , Almidón , Sumatriptán , Comprimidos , Sumatriptán/administración & dosificación , Sumatriptán/química , Trastornos Migrañosos/tratamiento farmacológico , Almidón/química , Almidón/análogos & derivados , Almidón/administración & dosificación , Quitosano/química , Humanos , Administración Oral , Solubilidad , Composición de Medicamentos , Química Farmacéutica , Excipientes/químicaRESUMEN
Imatinib, an ABL tyrosine-kinase inhibitor, shows promise in restoring endothelial barrier function in patients with COVID-19, thus, preventing cytokine leakage from the alveolar compartment to the systemic compartment. COVID-19 is characterized by an alveolar cytokine storm, and imatinib has been shown to strengthen the endothelial barrier and mitigate alveolar inflammatory responses by modulating NF-κB signaling. Incorporating imatinib into COVID-19 treatment strategies offers a novel approach to safeguard the endothelial barrier and address the complex pathophysiology of the disease, including its potential implications in long COVID. Given that endothelial dysfunction plays a central role in COVID-19 progression and long COVID development, protecting the endothelial barrier during acute infection is crucial in preventing the persistent endothelial dysfunction associated with long COVID.
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COVID-19 , Síndrome Post Agudo de COVID-19 , Humanos , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Piperazinas/farmacología , Benzamidas/uso terapéutico , Benzamidas/farmacologíaRESUMEN
An acquired loss of cognition in several cognitive domains that is severe enough to interfere with social or professional functioning is called dementia. As well as a moderately in-depth mental status examination by a clinician to identify impairments in memory, language, attention, visuospatial cognition, such as spatial orientation, executive function, and mood, the diagnosis of dementia requires a history evaluating for cognitive decline and impairment in daily activities, with confirmation from a close friend or family member. The start and organization of the cognitive assessment can be helped by short screening tests for cognitive impairment. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some types of neurons. It has been determined through an assessment that, at best, our understanding of the underlying processes is still rudimentary, which presents exciting new targets for further study as well as the development of diagnostics and drugs. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. We concentrate on a number of the animal models of memory problems that have been mentioned in this review article because dementia has numerous etiologies. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders are followed by those primary nucleation pathways responsible for cognitive impairment and dementia.
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Trastornos del Conocimiento , Disfunción Cognitiva , Demencia , Humanos , Demencia/diagnóstico , Demencia/complicaciones , Trastornos del Conocimiento/etiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/complicaciones , Función Ejecutiva , CogniciónRESUMEN
Inspired by the recently synthesized hexagonal boron nitride (h-BN) doped graphene, density functional theory (DFT) calculations were performed to evaluate the anodic properties of BN doped graphene (BN-G), graphene oxide (BN-GO) and reduced graphene oxide (BN-rGO) for Li/Na ion batteries (LIBs/NIBs). Our proposed materials show a semiconducting character with band gaps of 1.4, 0.67 and 0.45 eV for BN-G, BN-GO and BN-rGO, respectively. Among the three nanosheets, BN-rGO shows strong interaction behavior with Li/Na whereby the defected site exhibits high reactivity compared to the other adsorption sites. The adsorption energies are found to be about -4.72/-4.10 eV for Li/Na at the defected site, which are consecutively 3 and 2 times stronger than the adsorption energies of BN-G and BN-GO. It is predicted by partial density of states (PDOS) and band structure analysis that the nanosheets will exhibit metallic behavior through the adsorption process. Relatively low diffusion barriers are found to be about 0.47 and 0.22 eV when Li and Na moved from one adsorption site to another nearby adsorption site on BN-rGO. Among them, BN-rGO shows a high specific capacity, about 1583 and 1319 mA h g-1 for LIBs and NIBs. Therefore, the suitable adsorption energy with metallic behavior of the nanosheet combined with the high specific capacity confirm that BN-rGO is a promising anode candidate for Li/Na ion batteries.
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BACKGROUND: Posterior-stabilized (PS) and cruciate-retaining (CR) have been the most common tibial designs used in total knee arthroplasty. Ultra-congruent (UC) inserts are becoming popular because they preserve bone without relying on the posterior cruciate ligament balance and integrity. Despite increasing use, there is no consensus on how UC inserts perform versus PS and CR designs. METHODS: A comprehensive literature search of 5 online databases was performed for articles from January 2000 to July 2022 comparing the kinematic and clinical outcomes of PS or CR tibial inserts to UC inserts. There were nineteen studies included. There were 5 studies comparing UC to CR and 14 comparing UC to PS. Only one randomized controlled trial (RCT) was rated "good quality". RESULTS: For CR studies, pooled analyses showed no difference in knee flexion (n = 3, P = .33) or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (n = 2, P = .58). For PS studies, meta-analyses showed better anteroposterior stability (n = 4, P < .001) and more femoral rollback (n = 2, P < .001) for PS but no difference in knee flexion (n = 9, P = .55) or medio-lateral stability (n = 2, P = .50). There was no difference with WOMAC (n = 5, P = .26), Knee Society Score (n = 3, P = .58), Knee Society Knee Score (n = 4, P = .76), or Knee Society Function Score (n = 5, P = .51). CONCLUSION: Available data demonstrates there are no clinical differences between CR or PS and UC inserts in small short-term studies ending around 2 years after surgery. More importantly, high-quality research comparing all inserts is lacking, demonstrating a need for more uniform and longer-term studies beyond 5 years after surgery to justify increased UC usage.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Ligamento Cruzado Posterior , Humanos , Articulación de la Rodilla/cirugía , Diseño de Prótesis , Rango del Movimiento Articular , Ligamento Cruzado Posterior/cirugía , Osteoartritis de la Rodilla/cirugíaRESUMEN
This study was designed to evaluate the pre-reproductive and reproductive responses of Linum usitatissimum L. (flax, linseed plant) to different levels of Pb in the soil. Flax seeds were sown in garden soil-filled earthen pots and treated with three different levels of lead as lead chloride (150, 450, and 750 mg Pb kg-1 soil) except control, and each treatment was replicated three times. Growth and reproductive parameters and photosynthetic pigments were significantly reduced (p ≤ 0.05) for all treatments. Quantitatively, Chlorophyll b content decreased more than chlorophyll a and the amount of proline content in the leaves increased in lockstep with the increase of Pb levels in the soil. Pb was found in substantial amounts in the roots, shoots, and seeds. The pattern of Pb accumulation in different organs was root > shoot > seeds. Pb levels in seeds obtained from 750 mg Pb kg-1 soil-treated plants exceeded the permissible limits. Biological concentration factor (BCF), biological accumulation coefficient (BAC) and translocation factor (TF) values showed that roots of L. usitatissimum absorbed and accumulated a substantial quantity of Pb but translocated only a fraction of that to the shoots. Therefore, L. usitatissimum L. can be used in phytostabilization rather than phytoextraction of Pb.
This manuscript evaluates the potential of flaxseeds to cause biomagnification of lead (Pb) in the human body when grown under different concentrations of Pb and assessment of the risk posed to consumer health in a food chain. This study also provides insight to evaluate the uptake and extraction efficiency of Linum usitatissimum L. to remediate the Pb-polluted soil and use of Pb contaminated plant products (stem fibers and linseed oil) in an ecofriendly manner.
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Lino , Contaminantes del Suelo , Biodegradación Ambiental , Suelo , Plomo , Clorofila A , Contaminantes del Suelo/análisis , Raíces de Plantas/químicaRESUMEN
BACKGROUND: As surgical techniques continue to evolve, the optimal approach for revascularizing multi-vessel coronary artery disease (CAD) remains a matter of ongoing debate. Accordingly, our objective was to compare and contrast various surgical techniques utilized in the management of multi-vessel CAD. METHODS: A systematic literature review was performed using PubMed, Embase, and Cochrane central register of controlled trials from inception to May 2022. Random-effects network meta-analysis was performed for the primary outcome; target vessel revascularization (TVR), and secondary outcomes; mortality, major adverse cardiac and cerebrovascular events, postoperative myocardial infarction, new-onset atrial fibrillation, stroke, new-onset dialysis, in patients undergoing percutaneous coronary intervention (PCI) with a stent, off-pump coronary bypass graft, on-pump coronary artery bypass graft (ONCABG), hybrid coronary revascularization, minimally-invasive coronary artery bypass, or robot-assisted coronary artery bypass (RCAB) surgeries. RESULTS: A total of 8841 patients were included from 23 studies. The analysis showed that ONCABG had the highest freedom from TVR, with a mean (SD) absolute risk of 0.027 (0.029); although ONCABG was found to be superior to all other methods, it was only significantly better than first-generation stent PCI. While RCAB did not demonstrate significant superiority over other treatments, it showed a greater probability of preventing postoperative complications. Notably, no significant heterogeneity was calculated for any of the reported outcomes. CONCLUSIONS: ONCABG shows a better rank probability compared to all other techniques for preventing TVR, while RCAB offers greater freedom from most postoperative complications. However, given the absence of randomized controlled trials, these results should be interpreted with caution.
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BACKGROUND: Antiplatelet therapy is used to decrease the risk of graft failure post coronary artery bypass graft surgery. We aimed to compare dual antiplatelet therapy (DAPT) with monotherapy along with a comparison of Aspirin, Ticagrelor, Aspirin+Ticagrelor (A+T) and Aspirin+Clopidogrel (A+C) to determine the major and minor bleeding risk, risk of postoperative myocardial infarction (MI), stroke, and all-cause mortality (ACM). METHODS: Randomized Controlled Trials comparing the four groups were included. Odds ratio (OR) and Absolute Risk (AR) were employed to assess the mean and standard deviation (SD) with 95% confidence intervals (CI). The Bayesian random-effects model was used for statistical analysis. Risk difference and Cochran Q tests were used to calculate rank probability (RP) and heterogeneity, respectively. RESULTS: We included 10 trials, consisting of 21 arms and 3926 patients. For the risk of major and minor bleed, A + T and Ticagrelor showed the lowest mean value of 0.040 (0.043) and 0.067 (0.073), respectively, and the highest RP of being the safest group. While a direct comparison between DAPT and monotherapy resulted in an OR of 0.57 [0.34, 0.95] for the risk of minor bleed. A + T was found to have the highest RP and the lowest mean value in terms of ACM, MI, and stroke. CONCLUSION: No significant difference was found between monotherapy or dual-antiplatelet therapy for the major bleeding risk safety outcome, however DAPT was found to have a significantly higher rate of minor bleeding complications post-CABG. DAPT should be considered as the antiplatelet modality of choice post-CABG.
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Wireless communication has become an integral part of modern vehicles. However, securing the information exchanged between interconnected terminals poses a significant challenge. Effective security solutions should be computationally inexpensive, ultra-reliable, and capable of operating in any wireless propagation environment. Physical layer secret key generation has emerged as a promising technique, which leverages the inherent randomness of wireless-channel responses in amplitude and phase to generate high-entropy symmetric shared keys. The sensitivity of the channel-phase responses to the distance between network terminals makes this technique a viable solution for secure vehicular communication, given the dynamic behavior of these terminals. However, the practical implementation of this technique in vehicular communication is hindered by fluctuations in the communication link between line-of-sight (LoS) and non-line-of-sight (NLoS) conditions. This study introduces a key-generation approach that uses a reconfigurable intelligent surface (RIS) to secure message exchange in vehicular communication. The RIS improves the performance of key extraction in scenarios with low signal-to-noise ratios (SNRs) and NLoS conditions. Additionally, it enhances the network's security against denial-of-service (DoS) attacks. In this context, we propose an efficient RIS configuration optimization technique that reinforces the signals received from legitimate users and weakens the signals from potential adversaries. The effectiveness of the proposed scheme is evaluated through practical implementation using a 1-bit RIS with 64×64 elements and software-defined radios operating within the 5G frequency band. The results demonstrate improved key-extraction performance and increased resistance to DoS attacks. The hardware implementation of the proposed approach further validated its effectiveness in enhancing key-extraction performance in terms of the key generation and mismatch rates, while reducing the effect of the DoS attacks on the network.
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Flexible power sources are critical to achieve the wide adoption of portable and wearable electronics. Herein, a facile and general strategy of fabricating a fibrous electrode was developed by 3D active coating technology, in which a stepping syringe with electrode paste was synchronously injected onto a rotating conductive wire, distinguished from the conventional direct-write 3D printing without a current collector. A series of such electrodes with different coating weight can be fabricated accurately and efficiently by adjusting critical process parameters following a set of derived equations. The demonstrated fibrous Zn-MnO2 battery with a high commercial ε-MnO2 loading of 14.9 mg cm-2 onto a stainless steel wire shows a reasonable energy density of 108 mWh cm-3, while the fiber-shaped supercapacitor with commercial porous graphene exhibits a high capacitance of 142.9 F g-1 and good durability for bending 10,000 cycles. This work constructs a bridge between materials and fiber-shaped electrodes for flexible energy storage devices.
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The present review critically appraised the randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone and low-dose dexamethasonein patients with COVID-19 and reported pooled mortality risk estimates associated with these two dosing regimens of dexamethasone. The systematic searching of electronic databases was limited to randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone with low-dose dexamethasone in patients with COVID-19 requiring respiratory support. The primary outcome of interest in this review was all-cause mortality. A total of eight trials with 1800 patients randomized to receive intermediate to high-dose dexamethasone and 1715 patients randomized to low-dose dexamethasone were included. The meta-analysis of six trials revealed no significant difference in the risk of 28-day all-cause mortality between intermediate- to high-dose dexamethasone and low-dose dexamethasone (odds ratio 1.16, 95% confidence interval, 0.77-1.74). Similarly, the meta-analysis of five trials revealed no significant difference between the two doses regarding 60-day all-cause mortality (odds ratio 0.96, 95% confidence interval 0.74-1.26). The results suggest intermediate- to high-dose dexamethasone to be as effective as low-dose dexamethasone in reducing the risk of mortality among patients with COVID-19 requiring respiratory support. However, higher dexamethasone doses could expose patients with COVID-19 to an increased risk of adverse events, such as hyperglycemia.