Perception and behavior toward neuropsychiatric disorders in Saudi Arabia: A systematic review and quality assessment.

LAY ABSTRACT: In 2010, Saudi Arabia became the first country from the Gulf Cooperation Council states to join the World Mental Health Survey Initiative, which collaborates with Harvard University and has undertaken over 33 countries. The Saudi National Mental Health Survey revealed that 80% of Saudis with severe mental health disorders do not seek treatment. Considering the strong evidence set out in Saudi national study and the recommendations for future research, this systematic literature review was initiated to examine the most studied neurodevelopmental disorders reported in the Kingdom of Saudi Arabia to explore public knowledge, attitudes, and behaviors. Findings have shown that attention deficit hyperactivity disorder and autism spectrum disorder have been the most studied neurodevelopmental disorders in Saudi Arabia since 2010. However, various groups in Saudi society, including healthcare professionals, medical students, and the general public, lacked knowledge about these health conditions, often leading to stigmatized attitudes and behaviors toward people with attention deficit hyperactivity disorder and autism spectrum disorder. However, demographic data showed that most of the studies were carried out in the Central and Western provinces. More research is needed in all regions of the Kingdom of Saudi Arabia to contribute to the knowledge about mental health conditions of attention deficit hyperactivity disorder and autism spectrum disorder children and their parents to increase knowledge about neurodevelopmental disorders and mental health disorders in the Kingdom of Saudi Arabia, thereby enabling people to rethink their attitudes and behavior.

Knowledge, attitude, and awareness of cardiopulmonary resuscitation among university enrolled medical and non-medical students of Pakistan: An online study.

Objective: To evaluate the awareness, attitude and knowledge of cardiopulmonary resuscitation (CPR) among university-enrolled medical and non-medical undergraduate students of Pakistan. Methods: Cross-sectional online survey-based study was conducted across institutes in Pakistan from December, 2022 to January, 2023. The study involved university-enrolled undergraduate students across the country. The structured questionnaire was disseminated via Google forms. For statistical analysis, SPSS version 20 was used to analyze the data by applying independent sample t-tests and ANOVA. Results: A total of 249 responses were received. After the exclusion of two responses, the overall awareness score of participants was found to be 2.49 ± 1.33, attitude score of 4.09 ± 1.74, and knowledge score of 3.51 ± 2.13. Female respondents, medical students, unmarried (single), private institutes, and respondents with educated parents achieved relatively higher scores. The overall difference in awareness scores among different regions of Pakistan was also significant (p <0.05). Gender, region, and parental literacy rate also showed effects on participants' basic life support (BLS) and CPR knowledge (p <0.05). Conclusions: Overall knowledge and awareness were unsatisfactory and inadequate in university-enrolled undergraduate students, with no one getting a complete score on very basic knowledge questions. Significant differences in awareness, attitude, and knowledge among different regions, genders, and parental literacy rates were found.

Echocardiography in a critical care unit: a contemporary review.

INTRODUCTION: Echocardiography is a rapid, noninvasive, and complete cardiac assessment tool for patients with hemodynamic instability. Relevant articles were extracted after searching on databases by two reviewers and incorporated in this review in anarrative style. AREAS COVERED: his review provides an overview of the evidence for current practices in critical care units (CCUs), incorporating the use of echocardiography in different etiologies of shock. EXPERT OPINION: In an acute scenario, a basic echocardiographic study yields prompt diagnosis, allowing for the initiation of treatment. The most common pathologies in shocked patients are identified promptly using two-dimensional (2D) and M-mode echocardiography. A more comprehensive assessment can follow after patients have been stabilized. There are four types of shock: (i) cardiogenic shock, (ii) hypovolemic shock, (iii) obstructive shock, and (iv) septic shock. All of them can be readily identified by echocardiography. As echocardiography is increasingly being used in an intensive care setting, its applications and evidence base should be expanded by randomized controlled trials to demonstrate patient outcomes in critical care.

Improving selective targeting to cancer-associated fibroblasts by modifying liposomes with arginine based materials.

A library of arginine-like surface modifiers was tested to improve the targetability of DOPE:DOPC liposomes towards myofibroblasts in a tumour microenvironment. Liposomes were characterised using zeta potential and dynamic light scattering. Cell viability remained unchanged for all liposomes. Liposomes were encapsulated using doxorubicin (DOX) with an encapsulation efficiency >94%. The toxicity of DOX-loaded liposomes was calculated via half-maximal inhibitory concentration (IC50) for fibroblasts and myofibroblasts. These liposomes resulted in significantly lower IC50-values for myofibroblasts compared to fibroblasts, making them more toxic towards the myofibroblasts. Furthermore, a significant increase in cell internalisation was observed for myofibroblasts compared to fibroblasts, using fluorescein-loaded liposomes. Most importantly, a novel regression model was constructed to predict the IC50-values for different modifications using their physicochemical properties. Fourteen modifications (A-N) were used to train and validate this model; subsequently, this regression model predicted IC50-values for three new modifications (O, P and Q) for both fibroblasts and myofibroblasts. Predicted and measured IC50-values showed no significant difference for fibroblasts. For myofibroblasts, modification O showed no significant difference. This study demonstrates that the tested surface modifications can improve targeting to myofibroblasts in the presence of fibroblasts and hence are suitable drug delivery vehicles for myofibroblasts in a tumour microenvironment.

Development of Acoustically Active Nanocones Using the Host-Guest Interaction as a New Histotripsy Agent.

Histotripsy is a noninvasive and nonthermal ultrasound ablation technique, which mechanically ablates the tissues using very short, focused, high-pressured ultrasound pulses to generate dense cavitating bubble cloud. Histotripsy requires large negative pressures (≥28 MPa) to generate cavitation in the target tissue, guided by real-time ultrasound imaging guidance. The high cavitation threshold and reliance on real-time image guidance are potential limitations of histotripsy, particularly for the treatment of multifocal or metastatic cancers. To address these potential limitations, we have recently developed nanoparticle-mediated histotripsy (NMH) where perfluorocarbon (PFC)-filled nanodroplets (NDs) with the size of ∼200 nm were used as cavitation nuclei for histotripsy, as they are able to significantly lower the cavitation threshold. However, although NDs were shown to be an effective histotripsy agent, they pose several issues. Their generation requires multistep synthesis, they lack long-term stability, and determination of PFC concentration in the treatment dose is not possible. In this study, PFC-filled nanocones (NCs) were developed as a new generation of histotripsy agents to address the mentioned limitations of NDs. The developed NCs represent an inclusion complex of methylated ß-cyclodextrin as a water-soluble analog of ß-cyclodextrin and perfluorohexane (PFH) as more effective PFC derivatives for histotripsy. Results showed that NCs are easy to produce, biocompatible, have a size <50 nm, and have a quantitative complexation that allows us to directly calculate the PFH amount in the used NC dose. Results further demonstrated that NCs embedded into tissue-mimicking phantoms generated histotripsy cavitation "bubble clouds" at a significantly lower transducer amplitude compared to control phantoms, demonstrating the ability of NCs to function as effective histotripsy agents for NMH.

Nanoparticle-mediated histotripsy (NMH) using perfluorohexane 'nanocones'.

Nanoparticle-mediated histotripsy (NMH) is an ultrasound treatment strategy that combines acoustically sensitive nanoparticles with histotripsy. Previous NMH studies using perfluorocarbon (PFC) nanodroplets (ND's), ~200 nm in diameter, demonstrated that NMH can selectively generate cavitation by reducing the cavitation threshold from ~25-30 MPa to ~10-15 MPa. Recent studies have also shown that cavitation nucleation in NMH is directly caused by the incident negative pressure (p-) exposed to the PFC, as predicted by classical nucleation theory (CNT), suggesting that the NMH cavitation threshold is dependent on the total volume of PFC present in the focal region. In this study, we investigate the use of a newly developed NMH nanoparticle synthesized using an inclusion complex of methylated ß-cyclodextrin and perfluorohexane (PFH). These 'nanocones' (NCs) have advantages compared to previously used ND's due to their smaller size (~50 nm), simple synthesis method, higher stability and information of definite PFH amount carried by the NC. To test the hypothesis that NCs can reduce the NMH cavitation threshold similar to ND's, and that the NMH cavitation threshold is dependent upon the total PFH concentration, tissue phantoms containing concentrations of NCs ranging from 10-5 to 10-10 (ml PFH/ml water) were exposed to single cycle ultrasound pulses using a 500 kHz focused transducer where high speed imaging captured cavitation data. Results showed that NCs significantly reduced the histotripsy cavitation threshold to 11.0 MPa for a concentration of 10-5 (ml PFH/ml water), with the threshold increasing at lower concentrations. Finally, the ability of NCs to be used for effective NMH ablation was demonstrated in tissue phantoms containing red blood cells (RBCs). Overall, the results of the study support our hypotheses that NCs can be used for effective NMH therapy and that NC concentration has a predictable threshold-reducing effect.

Novel pyridine-2,4,6-tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type-2 diabetes mellitus: In vitro studies against yeast α- and ß-glucosidase and in silico molecular modeling.

A range of novel pyridine-2,4,6-tricarbohydrazide thiourea compounds (4a-i) were synthesized in good to excellent yields (63-92%). The enzyme inhibitory potentials of these compounds were investigated against α- and ß-glucosidases because these enzymes play a crucial role in treating type-2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50 38.22 ± 0.12 µM), compounds 4i (IC50 25.49 ± 0.67 µM), 4f (IC50 28.91 ± 0.43 µM), 4h (IC50 30.66 ± 0.52 µM), and 4e (IC50 35.01 ± 0.45 µM) delivered better inhibition against α-glucosidase and were quite inactive/completely inactive against ß-glucosidase. The structure-activity relationship of these compounds was developed and elaborated with the help of molecular docking studies.

An Efficient Synthesis of bi-Aryl Pyrimidine Heterocycles: Potential New Drug Candidates to Treat Alzheimer's Disease.

A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC50 = 0.04 ± 0.0001 µM for AChE and IC50 = 0.85 ± 0.0001 µM for BChE), the IC50 values of the synthesized compounds ranged from 3.73 ± 0.61 µM to 57.36 ± 0.22 µM for AChE and 4.81 ± 0.16 µM to 111.61 ± 0.53 µM for BChE. Among these tested compounds, 6j having a -CH3 group was found to be the most potent one against both enzymes (AChE, IC50 = 3.73 ± 0.61 µM; BChE, IC50 = 4.81 ± 0.16 µM). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.

Pyridine sulfonamide as a small key organic molecule for the potential treatment of type-II diabetes mellitus and Alzheimer's disease: In vitro studies against yeast α-glucosidase, acetylcholinesterase and butyrylcholinesterase.

This paper presents the efficient high yield synthesis of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4i) along with their α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities. The enzymes inhibition results showed the potential of synthesized compounds in controlling both type-II diabetes mellitus and Alzheimer's disease. In vitro biological investigations revealed that most of compounds were more active against yeast α-glucosidase than the reference compound acarbose (IC50 38.25±0.12µM). Among the tested series the compound 4c bearing 4-flouro benzyl group was noted to be the most active (IC50 25.6±0.2µM) against α-glucosidase, and it displayed weak inhibition activities against AChE and BChE. Compound 4a exhibited the most desired results against all three enzymes, as it was significantly active against all the three enzymes; α-glucosidase (IC50 32.2±0.3µM), AChE (IC50 50.2±0.8µM) and BChE (IC50 43.8±0.8µM). Due to the most favorable activity of 4a against the tested enzymes, for molecular modeling studies this compound was selected to investigate its pattern of interaction with α-glucosidase and AChE targets.

Novel pyridine-2,4,6-tricarbohydrazide derivatives: design, synthesis, characterization and in vitro biological evaluation as α- and ß-glucosidase inhibitors.

A range of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4h) were synthesized and its biological inhibition towards α- and ß-glucosidases was studied. Most of the compounds demonstrate to be active against α-glucosidase, and quite inactive/completely inactive against ß-glucosidase. A number of compounds were found to be more active against α-glucosidase than the reference compound acarbose (IC50 38.25±0.12µM); being compound 4d with the p-hydroxy phenyl motive the most active (IC50 20.24±0.72µM). Molecular modeling studies show the interactions of compound 4d with the active site of target α-glucosidase kinase.