BACKGROUND: Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes. The precise cause of epileptogenesis remains uncertain; nevertheless, the etiology of epilepsy may involve neuroinflammation, oxidative stress, and malfunction of the neurotransmitter system. OBJECTIVE: The goal of this investigation was to assess barbaloin's protective properties with respect to pentylenetetrazol (PTZ)-)-induced cognitive deficits in rats via antioxidative, anti-inflammatory, and neurotransmitter-modulating effects. METHODS: Wistar rats were subjected to PTZ [40 mg/kg (i.p.)], which induced cognitive decline. Behavior assessment using a kindling score, open-field test (OFT), novel object recognition test (NORT), and assays for superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), acetylcholinesterase (AChE), caspase-3, nitric oxide (NO), interleukins-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6, nuclear factor kappa-B (NF-κB), Bcl-2 and Bax, and neurotransmitter levels [GABA, DA, NE, and serotonin (5-HT)] were performed. RESULTS: The treatment of rats with barbaloin resulted in behavior improvement and significant changes in the levels of GSH, SOD, CAT, MDA, AChE, NO, IL-6, IL-1ß, TNF-α, NF-κB, caspase-3, Bcl-2, and Bax compared to the PTZ control group. Barbaloin treatment resulted in notable changes in neurotransmitter levels (GABA, NE, 5-HT, DA) compared to the PTZ group. CONCLUSIONS: The ongoing study has gathered evidence indicating that the injection of barbaloin has resulted in significant improvements in cognitive performance in rats. This is achieved by inhibiting oxidative stress, enhancing the activity of natural antioxidant enzymes, reducing cytokine levels, and increasing the levels of neurotransmitters in the brain. These results were detected in comparison to a PTZ control and can be attributed to the potent anti-inflammatory and antioxidant capabilities of barbaloin, which could be linked to its neuroprotective properties. Barbaloin may potentially increase cognitive decline and boost neuronal survival by altering the expression of Bax, caspase-3, Bcl-2.
Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we address them by enabling the multifunctionality in dual Z-scheme MoS2/WO3-x/AgBiS2 across photolysis, photo Fenton-like, and night catalysis. Defect, basal, and facet-engineered WO3-x is modified with MoS2 and AgBiS2, which extended its photoresponse from the UV-NIR region, inhibited carrier recombination, and reduced carrier transfer resistance. The electric field rearrangement leads to a flow of electrons from MoS2 and AgBiS2 to WO3-x and intensifies the electron population, which is crucial for night catalysis. When MoS2/WO3-x/AgBiS2 was employed against doxycycline hydrochloride (DOXH), it removed 95.65, 81.11, and 77.92 % of DOXH in 100 min during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. It also effectively removed 91.91, 98.17, 99.01, and 98.99 % of rhodamine B (RhB), Congo red (CR), methylene blue (MB), and methylene orange (MO) in Fenton reactions, respectively. ESR analysis consolidates the ROS generation feature of MoS2/WO3-x/AgBiS2 using H2O2 with and without irradiation. This work provides a strategy to eliminate the deficiencies of WO3-x and is conducive to the evolution of applications seeking to combat environmental and energy crises.
In scientific research, assessing the impact and influence of authors is crucial for evaluating their scholarly contributions. Whereas in literature, multitudinous parameters have been developed to quantify the productivity and significance of researchers, including the publication count, citation count, well-known h index and its extensions and variations. However, with a plethora of available assessment metrics, it is vital to identify and prioritize the most effective metrics. To address the complexity of this task, we employ a powerful deep learning technique known as the Multi-Layer Perceptron (MLP) classifier for the classification and the ranking purposes. By leveraging the MLP's capacity to discern patterns within datasets, we assign importance scores to each parameter using the proposed modified recursive elimination technique. Based on the importance scores, we ranked these parameters. Furthermore, in this study, we put forth a comprehensive statistical analysis of the top-ranked author assessment parameters, encompassing a vast array of 64 distinct metrics. This analysis gives us treasured insights in between these parameters, shedding light on the potential correlations and dependencies that may affect assessment outcomes. In the statistical analysis, we combined these parameters by using seven well-known statistical methods, such as arithmetic means, harmonic means, geometric means etc. After combining the parameters, we sorted the list of each pair of parameters and analyzed the top 10, 50, and 100 records. During this analysis, we counted the occurrence of the award winners. For experimental proposes, data collection was done from the field of Mathematics. This dataset consists of 525 individuals who are yet to receive their awards along with 525 individuals who have been recognized as potential award winners by certain well known and prestigious scientific societies belonging to the fields' of mathematics in the last three decades. The results of this study revealed that, in ranking of the author assessment parameters, the normalized h index achieved the highest importance score as compared to the remaining sixty-three parameters. Furthermore, the statistical analysis results revealed that the Trigonometric Mean (TM) outperformed the other six statistical models. Moreover, based on the analysis of the parameters, specifically the M Quotient and FG index, it is evident that combining these parameters with any other parameter using various statistical models consistently produces excellent results in terms of the percentage score for returning awardees.
Authorship , Humans , Bibliometrics , Algorithms , Deep Learning
OBJECTIVE: This study sought to elucidate clinical and imaging findings predictive for malperfusion syndrome after blunt thoracic aortic injury (BTAI). SUMMARY BACKGROUND DATA: There is limited literature on malperfusion syndrome after BTAI and the timing of thoracic endovascular aortic repair (TEVAR) in patients with this condition has not been defined. METHODS: A retrospective analysis of prospectively collected data of patients with BTAI treated between January 2021 and October 2023. Clinical and thoracic aortic (TA) imaging data, time to TEVAR, in-hospital death, and malperfusion/reperfusion sequelae (paraplegia, renal/visceral/limb ischemia, and compartment syndromes) were assessed. Correlations between clinical and imaging findings, time to TEVAR, and outcomes were evaluated. RESULTS: Of the 19,203 trauma patients evaluated, 13,717 (71%) had blunt injuries and 77 (0.6%) had BTAI. The majority (67.5%) were male with a median age of 40 years (IQR:33-55). TEVAR was performed in 42 (54.5%) patients. Seven (9.1%) patients presented with clinical and TA imaging criteria for traumatic thoracic aortic coarctation (TTAC), including diminished/absent femoral pulses and TA luminal narrowing of 50-99%. The median time to TEVAR was 9 (IQR:5-32), 11, and 4 hours for all non-TTAC and TTAC BTAI patients, respectively (P=0.037). Only TTAC patients presented/developed malperfusion/reperfusion sequelae. In-hospital mortality rates were 7.8%, 5.8%, and 29% for all non-TTAC and TTAC BTAI patients, respectively (P=0.09). Aortic-related mortality occurred in only two (2.6%) TTAC patients.. CONCLUSIONS: Patients with clinical and TA imaging manifestations of TTAC are predisposed to malperfusion/reperfusion sequelae if TEVAR is delayed. We recommend the emergent repair of all BTAIs with TTAC.
Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).
Introduction: Soil salinization poses a significant environmental challenge affecting plant growth and agricultural sustainability. This study explores the potential of salt-tolerant endophytes to mitigate the adverse effects of soil salinization, emphasizing their impact on the development and resistance of Arachis hypogaea L. (peanuts). Methods: The diversity of culturable plant endophytic bacteria associated with Miscanthus lutarioriparius was investigated. The study focused on the effects of Bacillus tequilensis, Staphylococcus epidermidis, and Bacillus siamensis on the development and germination of A. hypogaea seeds in pots subjected to high NaCl concentrations (200 mM L-1). Results: Under elevated NaCl concentrations, the inoculation of endophytes significantly (p < 0.05) enhanced seedling germination and increased the activities of enzymes such as Superoxide dismutase, catalase, and polyphenol oxidase, while reducing malondialdehyde and peroxidase levels. Additionally, endophyte inoculation resulted in increased root surface area, plant height, biomass contents, and leaf surface area of peanuts under NaCl stress. Transcriptome data revealed an augmented defense and resistance response induced by the applied endophyte (B. tequilensis, S. epidermidis, and B. siamensis) strain, including upregulation of abiotic stress related mechanisms such as fat metabolism, hormones, and glycosyl inositol phosphorylceramide (Na+ receptor). Na+ receptor under salt stress gate Ca2+ influx channels in plants. Notably, the synthesis of secondary metabolites, especially genes related to terpene and phenylpropanoid pathways, was highly regulated. Conclusion: The inoculated endophytes played a possible role in enhancing salt tolerance in peanuts. Future investigations should explore protein-protein interactions between plants and endophytes to unravel the mechanisms underlying endophyte-mediated salt resistance in plants.
BACKGROUND: Evidence-based medicine (EBM) has the potential to improve health outcomes, but EBM has not been widely integrated into the systems used for research or clinical decision-making. There has not been a scalable and reusable computer-readable standard for distributing research results and synthesized evidence among creators, implementers, and the ultimate users of that evidence. Evidence that is more rapidly updated, synthesized, disseminated, and implemented would improve both the delivery of EBM and evidence-based health care policy. OBJECTIVE: This study aimed to introduce the EBM on Fast Healthcare Interoperability Resources (FHIR) project (EBMonFHIR), which is extending the methods and infrastructure of Health Level Seven (HL7) FHIR to provide an interoperability standard for the electronic exchange of health-related scientific knowledge. METHODS: As an ongoing process, the project creates and refines FHIR resources to represent evidence from clinical studies and syntheses of those studies and develops tools to assist with the creation and visualization of FHIR resources. RESULTS: The EBMonFHIR project created FHIR resources (ie, ArtifactAssessment, Citation, Evidence, EvidenceReport, and EvidenceVariable) for representing evidence. The COVID-19 Knowledge Accelerator (COKA) project, now Health Evidence Knowledge Accelerator (HEvKA), took this work further and created FHIR resources that express EvidenceReport, Citation, and ArtifactAssessment concepts. The group is (1) continually refining FHIR resources to support the representation of EBM; (2) developing controlled terminology related to EBM (ie, study design, statistic type, statistical model, and risk of bias); and (3) developing tools to facilitate the visualization and data entry of EBM information into FHIR resources, including human-readable interfaces and JSON viewers. CONCLUSIONS: EBMonFHIR resources in conjunction with other FHIR resources can support relaying EBM components in a manner that is interoperable and consumable by downstream tools and health information technology systems to support the users of evidence.
Evidence-Based Medicine , Health Information Interoperability , Evidence-Based Medicine/standards , Humans , Health Information Interoperability/standards , COVID-19 , Health Level Seven
Fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a global pest causing damage to several crops. However, its management using chemical control is a challenge due to its capacity to evolve resistance to insecticides. After 6 generations of selection with lambda-cyhalothrin, the LC50 for the insecticide-resistant strain (Lambda-Sel) was 486 ppm, higher than that of the field strain (FAW-MUL) (7.5 ppm), susceptible laboratory strain (Lab-PK) (0.46 ppm), and laboratory unselected strain (UNSEL) (5.26 ppm). Laboratory selection with lambda-cyhalothrin increased resistance from 16.3- to 1056.52-fold and 1.43- to 92.4-fold to lambda-cyhalothrin compared to Lab-PK and UNSEL strains, respectively. The selected strain of S. frugiperda (Lambda-Sel) presented low cross-resistance to chlorpyrifos, moderate to deltamethrin and indoxacarb, very low to spinosad, and no cross-resistance to emamectin benzoate. The realized heritability (h2) of lambda-cyhalothrin resistance in the Lambda-Sel strain was very high (0.88). The reciprocal cross progenies of F1 (Lambda-Sel ââ ×â Lab-PK â), F1' (Lambda-Sel ââ ×â Lab-PK â), BC1 (F1 ââ ×â Lambda-Sel â), and BC2 (F1 ââ ×â Lab-PK â) showed high resistance ratios of 545.64-, 396.52-, 181.18-, and 146.54-fold, respectively compared to Lab-PK. The degree of dominance values for lambda-cyhalothrin in F1 and F1' indicates incompletely dominant resistance. The difference between observed and expected mortality in backcross populations (BC1 and BC2) revealed a polygenic resistance. In conclusion, the resistance to lambda-cyhalothrin was autosomal, incompletely dominant, and polygenic. These findings provide new insights for insect resistance management strategies to mitigate the occurrence of resistance in this global pest.
BACKGROUND: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally. OBJECTIVE: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers. METHODS: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1ß (IL-1ß), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets. RESULTS: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1ß, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol. CONCLUSION: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.
The fascinating world of microscopic life unveils a captivating spectacle as bacteria effortlessly maneuver through their surroundings with astonishing accuracy, guided by the intricate mechanism of chemotaxis. This review explores the complex mechanisms behind this behavior, analyzing the flagellum as the driving force and unraveling the intricate signaling pathways that govern its movement. We delve into the hidden costs and benefits of this intricate skill, analyzing its potential to propagate antibiotic resistance gene while shedding light on its vital role in plant colonization and beneficial symbiosis. We explore the realm of human intervention, considering strategies to manipulate bacterial chemotaxis for various applications, including nutrient cycling, algal bloom and biofilm formation. This review explores the wide range of applications for bacterial capabilities, from targeted drug delivery in medicine to bioremediation and disease control in the environment. Ultimately, through unraveling the intricacies of bacterial movement, we can enhance our comprehension of the intricate web of life on our planet. This knowledge opens up avenues for progress in fields such as medicine, agriculture, and environmental conservation.
Bacteria , Bacterial Physiological Phenomena , Chemotaxis , Biodegradation, Environmental
Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.
Fibrosarcoma , RNA, Untranslated , Humans , Fibrosarcoma/genetics , Fibrosarcoma/pathology , RNA, Untranslated/genetics , Gene Expression Regulation, Neoplastic , Oncogenes/genetics , Tumor Microenvironment/genetics , Genes, Tumor Suppressor/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , Animals
Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.
Carcinoma, Hepatocellular , Liver Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RNA, Untranslated , Signal Transduction , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Signal Transduction/genetics , RNA, Untranslated/genetics , Gene Expression Regulation, Neoplastic/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity. It aids in significant weight loss and improves obesity-related medical conditions. Despite its effectiveness, postoperative care still has challenges. Clinical evidence shows that venous thromboembolism (VTE) is a leading cause of 30-d morbidity and mortality after RYGB. Therefore, a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates. AIM: To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB. METHODS: Using the 2016-2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program, data from 6526 patients (body mass index ≥ 40 kg/m2) who underwent RYGB were analyzed. A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB. The resultant risk scores were derived from the coefficients of statistically significant variables. The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation. RESULTS: Of the 26 initial variables, six predictors were identified. These included a history of chronic obstructive pulmonary disease with a regression coefficient (Coef) of 2.54 (P < 0.001), length of stay (Coef 0.08, P < 0.001), prior deep venous thrombosis (Coef 1.61, P < 0.001), hemoglobin A1c > 7% (Coef 1.19, P < 0.001), venous stasis history (Coef 1.43, P < 0.001), and preoperative anticoagulation use (Coef 1.24, P < 0.001). These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB. The risk model's area under the curve (AUC) was 0.79 [95% confidence interval (CI): 0.63-0.81], showing good discriminatory power, achieving a sensitivity of 0.60 and a specificity of 0.91. Without training, the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63 (95%CI: 0.62-0.64) and endoscopic sleeve gastroplasty with an AUC of 0.76 (95%CI: 0.75-0.78). CONCLUSION: This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients, offering insights into factors that heighten the risk of VTE events.
Fire blight, a devastating disease caused by Erwinia amylovora, poses a significant threat to pear and apple trees in Xinjiang province, China. In an effort to combat this pathogen, we isolated 10 bacteria from various components of apple and crabapple trees and conducted screenings to assess their ability to inhibit E. amylovora in vitro. Through biochemical tests and partial 16S rRNA gene sequencing, we identified two promising strains, Priestia megaterium strain H1 and Bacillus subtilis strain I2. These strains were then evaluated for their efficacy in biocontrol under controlled laboratory conditions, focusing on immature fruits and leaves. Remarkably, all selected antagonists exhibited the capability to reduce the severity of the disease on both fruit and leaves. P. megaterium strain H1 and B. subtilis strain I2 exhibited significant reductions in disease incidence on both immature fruits and leaves compared to the control. Specifically, on immature fruits, they achieved reductions of 53.39% and 44.76%, respectively, while on leaves, they demonstrated reductions of 59.55% and 55.53%, respectively. Furthermore, during the study, we detected the presence of lipopeptides, including surfactin, iturins, bacillomycin D, and fengycins, in the methanol extract obtained from these two antagonistic bacteria using thin-layer chromatography (TLC). Based on the results obtained, B. subtilis strain I2 and P. megaterium strain H1 exhibit considerable potential for controlling fire blight. However, further evaluation of their efficacy under natural field conditions is essential to validate their practicality as a biocontrol method.
BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.
Autophagy , Parkinson Disease , RNA, Untranslated , Humans , Parkinson Disease/genetics , Parkinson Disease/pathology , Parkinson Disease/metabolism , Autophagy/physiology , Autophagy/genetics , RNA, Untranslated/genetics , Animals
BACKGROUND: Peridevice leak (PDL) after left atrial appendage closure (LAAC) portends adverse outcomes. OBJECTIVE: The purpose of this study was to assess the incidence, predictors, clinical implications, and temporal evolution of PDL after LAAC. METHODS: This single-center retrospective study included all patients who underwent LAAC with Watchman FLX and had no PDL detected at the time of implantation. The primary end point was the incidence of new PDL at initial imaging. The composite secondary end point included continued oral anticoagulation after initial imaging, device-related thrombus, stroke or transient ischemic attack, major bleeding, and need for PDL closure at longest follow-up. Temporal evolution of PDL was assessed in patients with available surveillance imaging. RESULTS: Of the 355 patients who completed imaging at 47 days (interquartile range [IQR] 6 days), 139 (39%) had new PDL with a mean leak size of 3.2 ± 1.4 mm (median 3.0 mm; IQR 2.0 mm; range 1.0-9.0 mm]. Multiple deployment attempts and larger device size were positive predictors of PDL, while increased contrast volume administration was a negative predictor of PDL. The composite secondary end point occurred in 42 (30%) and 33 (15%) patients with and without PDL, respectively (P < .001). Of the 139 patients with PDL, 43 (31%) had surveillance imaging where the leak size regressed from 3.7 ± 1.8 mm at 46 days (IQR 7 days) to 1.7 ± 2.0 mm at 189 days (IQR 127 days) (P < .001). The leak size regressed in 33 (77%), remained stable in 4 (9%), and progressed in 6 (14%) cases. CONCLUSION: Despite design improvements, LAAC with Watchman FLX demonstrates a significant incidence of PDL with meaningful clinical implications. Regardless of initial size, most leaks regressed over time.
Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.
Autophagy , Dopaminergic Neurons , Parkinson Disease , RNA, Untranslated , Parkinson Disease/genetics , Parkinson Disease/metabolism , Parkinson Disease/pathology , Humans , Autophagy/physiology , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , RNA, Untranslated/genetics , Animals
OBJECTIVE: Endoscopic ultrasonography (EUS) is an emerging method with a wide range of potential uses in gastroenterology, including the detection of bile duct stones and the identification of early ductal alterations in suspected patients. This study was designed to compare the diagnostic yield of EUS and transabdominal ultrasound (TUS) in the detection of gallbladder and common bile duct (CBD) microlithiasis. METHOD: Patients with biliary colic with normal initial TUS were the subjects of this prospective study. EUS scan was performed on all recruited patients and linear endoscopes were used for the EUS examination. Cholecystectomy and histological analysis were done in patients within two weeks after EUS revealing cholelithiasis whereas the cases of CBD stone/microlithiasis were confirmed by endoscopic retrograde cholangiopancreatography (ERCP). The mean values of all hematological characteristics were independently determined for males and females and then compared using Student's t-test. For statistical significance, a p-value of 0.05 or below was used. RESULTS: A total of 131 patients, including 77 females and 54 males, with a mean age of 38.41 ± 14.78 years were examined. All 78 (59.5%) individuals who had cholecystectomy were found to have gallstones or microlithiasis as successfully diagnosed by EUS. The sensitivity and specificity of EUS were 92.9% and 100%, respectively, for CBD stones and 98.8% and 100%, respectively, for the detection of gallbladder microlithiasis. The agreement between EUS and TUS was fair for CBD stones (κ = 0.214) and very weak for microlithiasis (κ = -0.093). CONCLUSION: EUS demonstrates a superior yield over TUS in detecting gallbladder stones and CBD microlithiasis, offering a more reliable diagnostic modality. LIMITATION: This was a single-center study.
