PURPOSE OF THE STUDY: The majority of classical antihypertensive drugs were mainly focused on the RAAS signaling pathways. Though these antihypertensive drugs control blood pressure (BP), they have mild to severe life-threatening effects. Unrevealing effective hypertensive targets for BP management is essential. The effective targets could emerge either from RAAS-dependent or RAAS-independent pathways and/or through the cross-talks among them.
RESULTS: Analyzing the physiopathological mechanisms of hypertension has the benefit of understanding the interactions between these systems which helps in better understanding of drug targets and the importance of emergence of novel therapeutics.
CONCLUSION: This review is about the signaling pathways involved in hypertension pathogenesis and their cross-talks and it contributes to a better understanding of the etiology of hypertension.
METHODS: Fe₃O₄-SiO₂ was prepared using a modified Stober method and used as a heterogeneous catalyst in an ultrasound-assisted transesterification reaction to produce biodiesel. The tests were designed by the Response surface methodology by considering the molar ratio of methanol to oil (M/O), catalyst weight percentage, and sonication time as independent factors. The produced biodiesel in diesel generator engines and the emission of pollutants were evaluated.
RESULTS: The optimal production conditions were determined using the response surface methodology, which included a molar ratio of 8.30, a catalyst weight percentage of 5.30, and a sonication time of 30.02 min. The Pareto analysis indicated that the sonication time is the most important factor in the sono-catalytic transesterification of waste oil. The evaluation of the produced fuel showed that with an increase in the percentage of biodiesel in the engine's fuel input, CO emissions decreased by 0.027 % and smoke levels by 24 %, while NOx levels increased by 495 ppm. Additionally, the increase in biodiesel percentage led to a rise in brake-specific power by 44.6 kW and brake-specific fuel consumption by 89 g/kWh though brake torque decreased by 87 Nm.
CONCLUSION: The study introduces significant advancements in biodiesel production technology through combining heterogeneous catalysis and ultrasound processing, optimizing production parameters for efficiency and sustainability while demonstrating improved environmental performance in diesel engines.
METHODS: The proposed MPa-DCAE model leverages the hierarchical feature extraction capabilities of VGG19 within a DCAE framework, designed to capture intricate patterns in histopathology images. By using a multi-patch approach, regions of interest are extracted from pathology images to facilitate localized feature learning, enhancing the model's discriminatory power. The auto-encoder component enables unsupervised feature learning, increasing resilience and adaptability to variations in image features. Experiments were conducted at various magnifications on the CBIS-DDSM and MIAS datasets to validate model performance.
RESULTS: Experimental results demonstrated that the MPa-DCAE model outperformed existing methods. For the CBIS-DDSM dataset, the model achieved a precision of 97.96%, a recall of 94.85%, and an accuracy of 98.36%. For the MIAS dataset, it achieved a precision of 97.99%, a recall of 97.2%, and an accuracy of 98.95%. These results highlight the model's robustness and potential for clinical application in computer-assisted diagnosis.
CONCLUSION: The MPa-DCAE model, integrating VGG19 and DCAE, proves to be an effective, automated approach for diagnosing breast cancer. Its high accuracy and generalizability make it a promising tool for clinical practice, potentially improving patient care in histopathology-based breast cancer diagnosis.
OBJECTIVE: This study aimed to design and develop the ChestCare mobile Health app using user-centred design (UCD) approach. Thus, it provided PTR for patients with COPD, enhancing their self-management of symptoms and improving their compliance with PR programs.
METHODS: In this mixed-methods sequential research, we deployed the UCD iterative design through the prototype app design and development sequence. The first phase was built based on the results of a previous needs assessment study and an analysis of related apps. This produced the initial mock-up, the foundation for the focus group discussions with physiotherapists and patients. Six physiotherapists with cardiorespiratory specialisation evaluated each app module and item of the latest mock-up using the content validity index (CVI) document. The I-CVI (S-CVI/Ave) and (S-CVI/UA) were computed. Qualitative and quantitative data were integrated, and decisions were made by comparing their results.
RESULTS: The UCD iterative design through sequential MMR has generated four mock-up app versions. The latest version identified 13 modules through 150 items validated by six experts using a CVI document. The I-CVI calculation of 145 items was 1, while 0.83 for the remaining items, was within accepted values. The S-CVI scored 99.4, indicating an overall validity of the ChestCare app as a PTR system for patients with COPD.
CONCLUSIONS: The development and validation of the ChestCare app resulted from conducting UCD iterative design and sequential MMR, which identified 13 functionalities, including symptom assessment, tracking lung volume, functional capacity test, action plan, intervention program, COPD education, COPD community, monitoring and reminders.
METHODS: PubMed, the Excerpta Medica dataBASE (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Advanced Search, and Turning Research Into Practice (TRIP) Database were systematically searched from inception to August 2023. The primary outcomes were knowledge level, knowledge scores, participation in shared decision-making (SDM), decisional conflict, and preference for SDM participation. Secondary outcomes were the proportion of subjects who underwent screening (actual screening utilisation) and the proportion of subjects who intended to be screened (intention to undergo screening). Network and pairwise meta-analyses were performed using random-effects models.
RESULTS: Seven systematic reviews were included. Network meta-analysis found that multimedia (relative risk [RR] 1.51, 95% confidence interval [CI] 1.02-2.24), print (RR 1.82, 95% CI 1.23-2.69), and website-based (RR 1.99, 95% CI 1.32-3.01) DAs significantly increased participation in SDM compared to the computer-based DA. There was a significant reduction in the actual screening utilisation in the computer DA arm compared to the other delivery modes. No significant differences between all delivery modes were noted on knowledge levels, knowledge scores, decisional conflict, preference for SDM participation, and intention to undergo screening. The highest mean surface under the cumulative ranking curve for all primary outcomes showed that website-based was the most effective delivery mode, followed by print-based DA. The pairwise meta-analysis showed a significant increase in participants' knowledge level, knowledge scores, a reduced intention to undergo screening and actual screening utilisation compared to UC.
CONCLUSIONS: The findings suggest that different types of DAs have varying levels of effectiveness in increasing knowledge level, knowledge scores, participation in SDM, and influencing screening behaviours. While website-based DA appeared the most effective, employing the print-based DA could be a practical solution in settings with limited resources.
METHODS: We undertook a retrospective review of all LB performed at our institution for suspected acute FB aspiration from August 2013 to January 2023. We analysed patient characteristics, clinical examination, radiological findings, and outcomes.
RESULTS: We found a total of 100 children under the age of 16 years who underwent LB for suspected FB aspiration. The mean age of our study population was 2.6 years. The population demographics were similar to the results from the previous study from our institution, with Māori and Pasifika children having the highest probability of finding a FB on LB. Male children presenting for suspected FB aspiration are 1.39 times more likely than female children to have a foreign body at LB (p = 0.04). Overall, having two or more positive findings had a sensitivity of 100 %. History or examination alone are more sensitive (both 95.6 %) but less specific (12.5 % and 31.3 %, respectively). Abnormal radiology alone was more specific (75.0) but less sensitive (77.9 %). The most common site of FB was the right bronchial tree (45.6 %), followed by the left (39.7 %). 95 % of FB were organic, and 54 % were nuts. The negative bronchoscopy rate was 32 %.
CONCLUSION: Two or more positive indicators in history, examination and radiological findings continue to be highly sensitive predictors for the presence of an aspirated foreign body in our paediatric population. We recommend a future large-scale multicentre study to confirm how applicable these findings would be to a broader cohort of patients.
METHODS: Participants (N = 750, Mage = 20.1 years) completed questionnaires assessing ACEs divided into adverse environment (AE) and childhood maltreatment (CM), exercise, and psychological distress. Salivary genomic DNA was used for genotyping. The significance of the moderated mediation model was assessed using bootstrapping.
RESULTS: There was a significant association between ACEs and psychological distress mediated by exercise. After addition of BDNF polymorphism, we found that the effect of ACEs on psychological distress through exercise was moderated by the BDNF polymorphism (index of moderated mediation = -0.19, [-0.48, -0.04], p-value ≤0.05). Further dividing ACE into AE and CM, the moderated mediation relationship remains significant only with AE (index of moderated mediation = -0.41, [-0.99, -0.10], p-value ≤0.05).
CONCLUSIONS: The interaction between BDNF polymorphism and exercise may be a suitable target for interventions in ACEs-experienced individuals for the prevention or reduction of psychological distress.
OBJECTIVES: This study aimed to examine two key drug repurposing methodologies in general diseases and specifically in AD, which are artificial intelligent (AI) approach and molecular docking approach. In addition, the hybrid approach that integrates AI with molecular docking techniques will be explored too.
METHODOLOGY: This study systematically compiled a comprehensive collection of relevant academic articles, scientific papers, and research studies which were published up until November 2024 (as of the writing of this review paper). The final selection of papers was filtered to include studies related to Alzheimer's disease and general diseases, and then categorized into three groups: AI articles, molecular docking articles, and hybrid articles.
RESULTS: As a result, 331 papers were identified that employed AI for drug repurposing in general diseases, and 58 papers focused specifically in AD. For molecular docking in drug repurposing, 588 papers addressed general diseases, while 46 papers were dedicated to AD. The hybrid approach combining AI and molecular docking in drug repurposing has 52 papers for general diseases and 9 for AD. A comparative review was done across the methods, results, strengths, and limitations in those studies. Challenges of drug repurposing in AD are explored and future prospects are proposed.
DISCUSSION AND CONCLUSION: Drug repurposing emerges as a compelling and effective strategy within AD research. Both AI and molecular docking methods exhibit significant potential in this domain. AI algorithms yield more precise predictions, thus facilitating the exploration of new therapeutic avenues for existing drugs. Similarly, molecular docking techniques revolutionize drug-target interaction modelling, employing refined algorithms to screen extensive drug databases against specific target proteins. This review offers valuable insights for guiding the utilization of AI, molecular docking, or their hybrid in AD drug repurposing endeavors. The hope is to speed up the timeline of drug discovery which could improve the therapeutic approach to AD.
METHODS: This was a prospective study of patients with normal renal anatomy who underwent FURS with FANS for renal stones from April 2023 to August 2024 in 16 centers worldwide. Thirty-day postoperative stone-free rate and delayed complications after 3 months were analyzed with a non-contrast CT scan and contrasted CT urogram respectively. The primary aim was to report if FANS could potentially cause pelviureteric junction, pelvicalyceal or ureteric complications.
RESULTS: Three hundred-ten patients were analyzed. Median age was 51; median stone volume was 1584 mm3. Disposable scopes were used in 58.1%. Predominant laser energies were Thulium fiber laser (56.1%) followed by Thulium-YAG laser (20.6%). Median laser time was 14 minutes, median ureteroscopy time was 30 minutes, and median total operation time was 45 minutes. Ureteric injury occurred in 11 patients (3.5%), of which 10 were Traxer-Thomas Grade 1. On 30-day NCCT, 63.5% of patients had zero residual fragments; overall stone-free status was seen in 95.1%. Thirty-day reintervention rate was 4.2% (13 cases). Three-month CT urogram showed ureteric stenosis in only 1 patient (0.3%) who was managed by dilatation and stenting. No other anatomical anomalies were recorded.
CONCLUSION: The extremely low rates of 3-month adverse outcomes, high immediate SFR, and low 30-day reintervention rates further strengthen the evidence for safety and effectiveness of FANS.
METHODS: In this pragmatic, multicentre, parallel-group, unmasked, randomised, non-inferiority trial, children aged 5-16 years with suspected non-perforated appendicitis (based on clinical diagnosis with or without radiological diagnosis) were recruited from 11 children's hospitals in Canada, the USA, Finland, Sweden, and Singapore. Patients were randomly assigned (1:1) to the antibiotic or the appendicectomy group with an online stratified randomisation tool, with stratification by sex, institution, and duration of symptoms (≥48 h vs <48 h). The primary outcome was treatment failure within 1 year of random assignment. In the antibiotic group, failure was defined as removal of the appendix, and in the appendicectomy group, failure was defined as a normal appendix based on pathology. In both groups, failure was also defined as additional procedures related to appendicitis requiring general anaesthesia. Interim analysis was done to determine whether inferiority was to be declared at the halfway point. We used a non-inferiority design with a margin of 20%. All outcomes were assessed in participants with 12-month follow-up data. The trial was registered at ClinicalTrials.gov (NCT02687464).
FINDINGS: Between Jan 20, 2016, and Dec 3, 2021, 936 patients were enrolled and randomly assigned to appendicectomy (n=459) or antibiotics (n=477). At 12-month follow-up, primary outcome data were available for 846 (90%) patients. Treatment failure occurred in 153 (34%) of 452 patients in the antibiotic group, compared with 28 (7%) of 394 in the appendicectomy group (difference 26·7%, 90% CI 22·4-30·9). All but one patient meeting the definition for treatment failure with appendicectomy were those with negative appendicectomies. Of those who underwent appendicectomy in the antibiotic group, 13 (8%) had normal pathology. There were no deaths or serious adverse events in either group. The relative risk of having a mild-to-moderate adverse event in the antibiotic group compared with the appendicectomy group was 4·3 (95% CI 2·1-8·7; p<0·0001).
INTERPRETATION: Based on cumulative failure rates and a 20% non-inferiority margin, antibiotic management of non-perforated appendicitis was inferior to appendicectomy.
FUNDING: None.