Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung

Introduction Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. Methods We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air–liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (Vt), short circuit current (Isc), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Results Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced Vt, the amiloride-sensitive Isc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Conclusion Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo

A Systematic Review of the Application of Artificial Intelligence in Nursing Care: Where are We, and What’s Next?

Suebsarn Ruksakulpiwat,1 Sutthinee Thorngthip,2 Atsadaporn Niyomyart,3 Chitchanok Benjasirisan,1 Lalipat Phianhasin,1 Heba Aldossary,4 Bootan Hasan Ahmed,5 Thanistha Samai6 1Department of Medical Nursing, Faculty of Nursing, Mahidol University, Bangkok, Thailand; 2Department of Nursing Siriraj Hospital, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Ramathibodi School of Nursing, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Department of Nursing, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia; 5Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 6Department of Public Health Nursing, Faculty of Nursing, Mahidol University, Nakhon Pathom, ThailandCorrespondence: Suebsarn Ruksakulpiwat, Email [email protected]: Integrating Artificial Intelligence (AI) into healthcare has transformed the landscape of patient care and healthcare delivery. Despite this, there remains a notable gap in the existing literature synthesizing the comprehensive understanding of AI’s utilization in nursing care.Objective: This systematic review aims to synthesize the available evidence to comprehensively understand the application of AI in nursing care.Methods: Studies published between January 2019 and December 2023, identified through CINAHL Plus with Full Text, Web of Science, PubMed, and Medline, were included in this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guided the identification, screening, exclusion, and inclusion of articles. The convergent integrated analysis framework, as proposed by the Joanna Briggs Institute, was employed to synthesize data from the included studies for theme generation.Results: A total of 337 records were identified from databases. Among them, 35 duplicates were removed, and 302 records underwent eligibility screening. After applying inclusion and exclusion criteria, eleven studies were deemed eligible and included in this review. Through data synthesis of these studies, six themes pertaining to the use of AI in nursing care were identified: 1) Risk Identification, 2) Health Assessment, 3) Patient Classification, 4) Research Development, 5) Improved Care Delivery and Medical Records, and 6) Developing a Nursing Care Plan.Conclusion: This systematic review contributes valuable insights into the multifaceted applications of AI in nursing care. Through the synthesis of data from the included studies, six distinct themes emerged. These findings not only consolidate the current knowledge base but also underscore the diverse ways in which AI is shaping and improving nursing care practices.Keywords: artificial intelligence, nursing care, patient care, systematic revie

Immunity, Sex Hormones, and Environmental Factors as Determinants of COVID-19 Disparity in Women

The current coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in a major global pandemic, causing extreme morbidity and mortality. Few studies appear to suggest a significant impact of gender in morbidity and mortality, where men are reported at a higher risk than women. The infectivity, transmissibility, and varying degree of disease manifestation (mild, modest, and severe) in population studies reinforce the importance of a number of genetic and epigenetic factors, in the context of immune response and gender. The present review dwells on several contributing factors such as a stronger innate immune response, estrogen, angiotensin-converting enzyme 2 gene, and microbiota, which impart greater resistance to the SARS-CoV-2 infection and disease progression in women. In addition, the underlying importance of associated microbiota and certain environmental factors in gender-based disparity pertaining to the mortality and morbidity due to COVID-19 in women has also been addressed.Institute for Research and Medical Consultatio

Boundaries and Future Trends of ChatGPT Based on AI and Security Perspectives

In decades, technology and artificial intelligence have significantly impacted aspects of life. One noteworthy development is ChatGPT, an AI-based model that has created a revolution and attracted attention from researchers, academia, and organizations in a short period of time. Experts predict that ChatGPT will continue advancing, bringing about a leap in artificial intelligence. It is believed that this technology holds the potential to address cybersecurity concerns, protect against threats and attacks, and overcome challenges associated with our increasing reliance on technology and the internet. This technology may change our lives in productive and helpful ways, from the interaction with other AI technologies to the potential for enhanced personalization and customization to the continuing improvement of language model performance. While these new developments have the potential to enhance our lives, it is our responsibility as a society to thoroughly examine and confront the ethical and societal impacts. This research delves into the state of ChatGPT and its developments in the fields of artificial intelligence and security. It also explores the challenges faced by ChatGPT regarding privacy, data security, and potential misuse. Furthermore, it highlights emerging trends that could influence the direction of ChatGPT's progress. This paper also offers insights into the implications of using ChatGPT in security contexts. Provides recommendations for addressing these issues. The goal is to leverage the capabilities of AI-powered conversational systems while mitigating any risks.   Doi: 10.28991/HIJ-2024-05-01-010 Full Text: PD

Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival

The authors aim to develop siRNA therapeutics for cancer that can be administered systemically to target tumors and retard their growth. The efficacy of systemic delivery of siRNA to tumors with nanoparticles based on lipids or polymers is often compromised by their rapid clearance from the circulation by the liver. Here, multifunctional cationic and anionic siRNA nanoparticle formulations are described, termed receptor‐targeted nanocomplexes (RTNs), that comprise peptides for siRNA packaging into nanoparticles and receptor‐mediated cell uptake, together with lipids that confer nanoparticles with stealth properties to enhance stability in the circulation, and fusogenic properties to enhance endosomal release within the cell. Intravenous administration of RTNs in mice leads to predominant accumulation in xenograft tumors, with very little detected in the liver, lung, or spleen. Although non‐targeted RTNs also enter the tumor, cell uptake appears to be RGD peptide‐dependent indicating integrin‐mediated uptake. RTNs with siRNA against MYCN (a member of the Myc family of transcription factors) in mice with MYCN‐amplified neuroblastoma tumors show significant retardation of xenograft tumor growth and enhanced survival. This study shows that RTN formulations can achieve specific tumor‐targeting, with minimal clearance by the liver and so enable delivery of tumor‐targeted siRNA therapeutics

Non prescribed sale of antibiotics in Riyadh, Saudi Arabia: A Cross Sectional Study

Background Antibiotics sales without medical prescriptions are increasingly recognized as sources of antimicrobial misuse that can exacerbate the global burden of antibiotic resistance. We aimed to determine the percentage of pharmacies who sell antibiotics without medical prescriptions, examining the potential associated risks of such practice in Riyadh, Saudi Arabia, by simulation of different clinical scenarios. Methods A cross sectional study of a quasi-random sample of pharmacies stratified by the five regions of Riyadh. Each pharmacy was visited once by two investigators who simulated having a relative with a specific clinical illness (sore throat, acute bronchitis, otitis media, acute sinusitis, diarrhea, and urinary tract infection (UTI) in childbearing aged women). Results A total of 327 pharmacies were visited. Antibiotics were dispensed without a medical prescription in 244 (77.6%) of 327, of which 231 (95%) were dispensed without a patient request. Simulated cases of sore throat and diarrhea resulted in an antibiotic being dispensed in (90%) of encounters, followed by UTI (75%), acute bronchitis (73%), otitis media (51%) and acute sinusitis (40%). Metronidazole (89%) and ciprofloxacin (86%) were commonly given for diarrhea and UTI, respectively, whereas amoxicillin/clavulanate was dispensed (51%) for the other simulated cases. None of the pharmacists asked about antibiotic allergy history or provided information about drug interactions. Only 23% asked about pregnancy status when dispensing antibiotics for UTI-simulated cases. Conclusions We observed that an antibiotic could be obtained in Riyadh without a medical prescription or an evidence-based indication with associated potential clinical risks. Strict enforcement and adherence to existing regulations are warranted

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Dental caries in primary and permanent teeth in children's worldwide, 1995 to 2019: a systematic review and meta-analysis

Background: Early childhood caries (ECC) is a type of dental caries in the teeth of infants and children that is represented as one of the most prevalent dental problems in this period. Various studies have reported different types of prevalence of dental caries in primary and permanent teeth in children worldwide. However, there has been no comprehensive study to summarize the results of these studies in general, so this study aimed to determine the prevalence of dental caries in primary and permanent teeth in children in different continents of the world during a systematic review and meta-analysis. Methods: In this review study, articles were extracted by searching in the national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science (ISI) between 1995 and December 2019. Random effects model was used for analysis and heterogeneity of studies was evaluated by using the I2 index. Data were analyzed by using the Comprehensive Meta-Analysis (Version 2) software. Findings: In this study, a total of 164 articles (81 articles on the prevalence of dental caries in primary teeth and 83 articles on the prevalence of dental caries in permanent teeth) were entered the meta-analysis. The prevalence of dental caries in primary teeth in children in the world with a sample size of 80,405 was 46.2% (95% CI: 41.6–50.8%), and the prevalence of dental caries in permanent teeth in children in the world with a sample size of 1,454,871 was 53.8% (95% CI: 50–57.5%). Regarding the heterogeneity on the basis of meta-regression analysis, there was a significant difference in the prevalence of dental caries in primary and permanent teeth in children in different continents of the world. With increasing the sample size and the year of study, dental caries in primary teeth increased and in permanent teeth decreased. Conclusion: The results of this study showed that the prevalence of primary and permanent dental caries in children in the world was found to be high. Therefore, appropriate strategies should be implemented to improve the aforementioned situation and to troubleshoot and monitor at all levels by providing feedback to hospitals