Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various ß-cyclodextrin derivatives using advanced computational techniques and experimental validation.

Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with ß-cyclodextrin (ßCD) and its three analogs, dimethyl-ß-cyclodextrin (DMßCD), hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4',6'-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with ßCDs through two distinct orientations, with OXY/SBEßCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEßCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEßCD (2060 M-1), HPßCD (1860 M-1), DMßCD (1700 M-1), and ßCD (1420 M-1). All complexes exhibited a 1:1 binding mode (AL type), with SBEßCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMßCD, OXY/HPßCD, and OXY/SBEßCD were markedly superior compared to that of OXY alone.

3D Printing of Alginate/Chitosan-Based Scaffold Empowered by Tyrosol-Loaded Niosome for Wound Healing Applications: In Vitro and In Vivo Performances.

This study introduces a tyrosol-loaded niosome integrated into a chitosan-alginate scaffold (Nio-Tyro@CS-AL), employing advanced electrospinning and 3D printing techniques for wound healing applications. The niosomes, measuring 185.40 ± 6.40 nm with a polydispersity index of 0.168 ± 0.012, encapsulated tyrosol with an efficiency of 77.54 ± 1.25%. The scaffold's microsized porous structure (600-900 µm) enhances water absorption, promoting cell adhesion, migration, and proliferation. Mechanical property assessments revealed the scaffold's enhanced resilience, with niosomes increasing the compressive strength, modulus, and strain to failure, indicative of its suitability for wound healing. Controlled tyrosol release was demonstrated in vitro, essential for therapeutic efficacy. The scaffold exhibited significant antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus, with substantial biofilm inhibition and downregulation of bacterial genes (ndvb and icab). A wound healing assay highlighted a notable increase in MMP-2 and MMP-9 mRNA expression and the wound closure area (69.35 ± 2.21%) in HFF cells treated with Nio-Tyro@CS-AL. In vivo studies in mice confirmed the scaffold's biocompatibility, showing no significant inflammatory response, hypertrophic scarring, or foreign body reaction. Histological evaluations revealed increased fibroblast and macrophage activity, enhanced re-epithelialization, and angiogenesis in wounds treated with Nio-Tyro@CS-AL, indicating effective tissue integration and repair. Overall, the Nio-Tyro@CS-AL scaffold presents a significant advancement in wound-healing materials, combining antibacterial properties with enhanced tissue regeneration, and holds promising potential for clinical applications in wound management.

Enhancing solubility and stability of piperine using ß-cyclodextrin derivatives: computational and experimental investigations.

Piperine (PP), a natural alkaloid found in black pepper, possesses significant bioactivities. However, its use in pharmaceutical applications is hindered by low water solubility and susceptibility to UV light degradation. To overcome these challenges, we investigated the potential of ß-cyclodextrin (ßCD) and its derivatives with dimethyl (DMßCD), hydroxy-propyl (HPßCD) and sulfobutyl-ether (SBEßCD) substitutions to enhance the solubility and stability of PP. This study employed computational and experimental approaches to examine the complexation between PP and ßCDs. The results revealed the formation of two types of inclusion complexes: the P-form and M-form involving the insertion of piperidine moiety and the methylene-di-oxy-phenyl moiety, respectively. These complexes primarily rely on van der Waals interactions. Among the three derivatives, the PP/SBEßCD complex exhibited the highest stability followed by HPßCD, as attributed to maximum atom contacts and minimal solvent accessibility. Solubility studies confirmed the formation of inclusion complexes in a 1:1 ratio. Notably, the stability constant of the inclusion complex was approximately two-fold higher with SBEßCD and HPßCD compared to ßCD. The DSC thermograms provided confirmation of the formation of the inclusion complex between the host and guest. These findings highlight the potential of ßCD derivatives to effectively encapsulate PP, improving its solubility and presenting new opportunities for its pharmaceutical applications.Communicated by Ramaswamy H. Sarma.

Enhancing solubility and stability of sorafenib through cyclodextrin-based inclusion complexation: in silico and in vitro studies.

Sorafenib (SOR) is an oral multikinase inhibitor that effectively hampers the growth and spread of cancer cells by targeting angiogenesis and proliferation. However, SOR tablets (Nexavar) have limited oral bioavailability, ranging from 38% to 49%, due to their low water solubility. To address this issue, cyclodextrins (CDs), widely used to enhance the solubility and stability of lipophilic drugs by encapsulating them within their molecular structure, were considered in this study. We focused on ß-cyclodextrin (ßCD) and its derivatives, including hydroxypropyl-ß-cyclodextrin (HPßCD), dimethyl-ß-cyclodextrin (DMßCD), sulfobutylether-ß-cyclodextrin (SBEßCD), and compared them with γ-cyclodextrin (γCD) for generating inclusion complexes with SOR. The 200 ns molecular dynamics simulations revealed that SOR could form inclusion complexes with all CDs in two possible orientations: pyridine group insertion (P-form) and chlorobenzotrifluoride group insertion (C-form), primarily driven by van der Waals interactions. Among the four ßCD derivatives studied, SOR exhibited the highest number of atom contacts with SBEßCD and demonstrated the lowest solvent accessibility within the hydrophobic cavity of SBEßCD. These findings correlated with the highest binding affinity of SOR/SBEßCD complex determined by SIE, MM/GBSA, and MM/PBSA methods. Experimental results further supported our computational predictions, in which SBEßCD exhibited a stability constant of 940 M-1 at 25 °C, surpassing ßCD's stability constant of 210 M-1. Taken together, our results suggest that the modified CDs, particularly SBEßCD, hold promising potential as an efficient molecular encapsulating agent for SOR, offering improved solubility and stability for this lipophilic drug.

Cellular mechanisms in the pathogenesis of interstitial lung diseases.

The interstitial lung diseases (ILDs) are a large, heterogeneous group of several hundred generally rare pulmonary pathologies, which show injury, inflammation and/or scarring in the lung. Although the aetiology of these disorders remains largely unknown, various cellular mechanisms have an important role in pathogenesis of fibrosis on the background of occupational, environmental and genetic factors. We have tried to provide new insights into the interactions and cellular contributions, analysing the roles of various cells in the pathogenesis of idiopathic pulmonary fibrosis.

A systematic review: Virtual-reality-based techniques for human exercises and health improvement.

Virtual Reality (VR) has emerged as a new safe and efficient tool for the rehabilitation of many childhood and adulthood illnesses. VR-based therapies have the potential to improve both motor and functional skills in a wide range of age groups through cortical reorganization and the activation of various neuronal connections. Recently, the potential for using serious VR-based games that combine perceptual learning and dichoptic stimulation has been explored for the rehabilitation of ophthalmological and neurological disorders. In ophthalmology, several clinical studies have demonstrated the ability to use VR training to enhance stereopsis, contrast sensitivity, and visual acuity. The use of VR technology provides a significant advantage in training each eye individually without requiring occlusion or penalty. In neurological disorders, the majority of patients undergo recurrent episodes (relapses) of neurological impairment, however, in a few cases (60-80%), the illness progresses over time and becomes chronic, consequential in cumulated motor disability and cognitive deficits. Current research on memory restoration has been spurred by theories about brain plasticity and findings concerning the nervous system's capacity to reconstruct cellular synapses as a result of interaction with enriched environments. Therefore, the use of VR training can play an important role in the improvement of cognitive function and motor disability. Although there are several reviews in the community employing relevant Artificial Intelligence in healthcare, VR has not yet been thoroughly examined in this regard. In this systematic review, we examine the key ideas of VR-based training for prevention and control measurements in ocular diseases such as Myopia, Amblyopia, Presbyopia, and Age-related Macular Degeneration (AMD), and neurological disorders such as Alzheimer, Multiple Sclerosis (MS) Epilepsy and Autism spectrum disorder. This review highlights the fundamentals of VR technologies regarding their clinical research in healthcare. Moreover, these findings will raise community awareness of using VR training and help researchers to learn new techniques to prevent and cure different diseases. We further discuss the current challenges of using VR devices, as well as the future prospects of human training.

Single-Cell Analysis Reveals Distinct Immune and Smooth Muscle Cell Populations that Contribute to Chronic Thromboembolic Pulmonary Hypertension.

Rationale: Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of acute pulmonary embolism (PE) in which the PE remodels into a chronic scar in the pulmonary arteries. This results in vascular obstruction, pulmonary microvasculopathy, and pulmonary hypertension. Objectives: Our current understanding of CTEPH pathobiology is primarily derived from cell-based studies limited by the use of specific cell markers or phenotypic modulation in cell culture. Therefore, our main objective was to identify the multiple cell types that constitute CTEPH thrombusy and to study their dysfunction. Methods: Here we used single-cell RNA sequencing of tissue removed at the time of pulmonary endarterectomy surgery from five patients to identify the multiple cell types. Using in vitro assays, we analyzed differences in phenotype between CTEPH thrombus and healthy pulmonary vascular cells. We studied potential therapeutic targets in cells isolated from CTEPH thrombus. Measurements and Main Results: Single-cell RNA sequencing identified multiple cell types, including macrophages, T cells, and smooth muscle cells (SMCs), that constitute CTEPH thrombus. Notably, multiple macrophage subclusters were identified but broadly split into two categories, with the larger group characterized by an upregulation of inflammatory signaling predicted to promote pulmonary vascular remodeling. CD4+ and CD8+ T cells were identified and likely contribute to chronic inflammation in CTEPH. SMCs were a heterogeneous population, with a cluster of myofibroblasts that express markers of fibrosis and are predicted to arise from other SMC clusters based on pseudotime analysis. Additionally, cultured endothelial, smooth muscle, and myofibroblast cells isolated from CTEPH fibrothrombotic material have distinct phenotypes from control cells with regard to angiogenic potential and rates of proliferation and apoptosis. Last, our analysis identified PAR1 (protease-activated receptor 1) as a potential therapeutic target that links thrombosis to chronic PE in CTEPH, with PAR1 inhibition decreasing SMC and myofibroblast proliferation and migration. Conclusions: These findings suggest a model for CTEPH similar to atherosclerosis, with chronic inflammation promoted by macrophages and T cells driving vascular remodeling through SMC modulation, and suggest new approaches for pharmacologically targeting this disease.

Decentering the use of police: An abolitionist approach to safety planning in psychotherapy.

The dominant narrative in much of the world, but especially the West, is that public safety and security are provided by policing. Psychotherapy invests in this dominant narrative via its reliance on emergency services provided by the state, such as 911 and police, to pursue the safety of clients and the larger society. However, the long-documented history of oppressive systems of policing suggest that these dominant narratives operate to protect powerful groups while surveilling and policing marginalized people, but particularly Black and Brown communities. As such, critical and abolitionist movements have rejected the idea that policing provides safety and have sought out alternative methods for ensuring community wellness and safety. Although the field of psychology has broadly expressed interest in growing its critical lens and interrupting systems of power, very little has directly addressed how carceral logics influence psychotherapy practice, and how this influences the client's sense of safety in therapy. This manuscript argues for an abolitionist approach to informed consent and safety planning in psychotherapy to address the disparate ways that clients, and especially marginalized clients such as Black and Brown people, experience psychotherapy's traditional use of systems of policing and state authority. Clinical illustrations are provided and future directions are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Bone Marrow Collection: Comparison of Unassisted vs Assisted Bedside Collections by a Laboratory Technologist.

OBJECTIVES: Bone marrow collections are often difficult, and creating quality smears and touch preparations at the bedside can prove challenging. The objective of this study is to compare the quality of bone marrow specimens between unassisted and assisted bone marrow collections by a bone marrow technologist. METHODS: Data for this study were collected from 422 hematopathology reports over 14 months. We recorded the bone marrow quality of the different parts (aspirate smears, touch imprints, core biopsy, and clot/particle sections) as adequate, suboptimal, or inadequate. Student t test statistical analysis was performed between the corresponding parts in the two groups. RESULTS: Our results demonstrate that the quality of assisted bone marrow specimens is significantly better compared with unassisted specimens, particularly for the aspirate smears (P < .0001) and touch imprints (P < .0001). Notably, the quality of aspirate smears was improved, which is important for cytologic evaluation. CONCLUSIONS: We conclude that assistance by a bone marrow technologist resulted in a significant improvement in the quality of bone marrow collection.

A pharmacist-delivered smoking cessation program in Qatar: an exploration of pharmacists' and patients' perspectives of the program.

Background Tobacco use is one of the major causes of morbidity and mortality. An intensive pharmacist-delivered smoking cessation program was implemented in eight primary care pharmacies in Qatar. Objective This study aimed to qualitatively explore the perspectives of pharmacists and patients regarding their experiences in the program and their recommendations for improving it. Setting Primary care in Doha, Qatar. Method This study used a qualitative case study approach with semi-structured interviews of a sample of patients and pharmacists who participated in the program. Interviews were conducted between October 2016 and June 2017, were audio-recorded and transcribed verbatim. A thematic approach for data analysis was used. Main outcome measures Perspectives of pharmacists and patients. Results Pharmacists who delivered the program (n = 17) and patients who completed the program's outcomes assessment (n = 68) were invited through telephone call or email. Eight pharmacists and 22 patients were interviewed. Seven themes emerged: (1) both pharmacists and patients had positive experiences and both considered pharmacists as among the most suitable healthcare providers to provide smoking cessation interventions (2) both pharmacist and patient participants indicated that the program provided successful services (3) pharmacists identified several challenges for implementing the program including difficulty in motivating and in following-up patients, workplace barriers, communication and cultural barriers, (4) both pharmacists and patients perceived several barriers for quitting including lack of motivation to quit or to commit to the plan, high nicotine dependence, stress and personal problems (5) both pharmacists and patients considered several patient-related facilitators for quitting including development of smoking related complications, religious beliefs and external support; (6) use of smoking cessation medications was considered a program-related facilitator for quitting by patients whereas behavioral therapy was perceived to be a facilitator by pharmacists (7) pharmacists and patients proposed strategies for program improvement including enhancing pharmacist training and patient recruitment. Conclusion The program was perceived to be beneficial in helping patients quit smoking, and it positively contributed to advancing pharmacist role. The study findings can guide future development of successful pharmacist' smoking cessation programs in Qatar.

Healthcare career intervention with youth in a predominantly Latinx rural community: a pilot study of a creative approach.

The present study discusses a pilot intervention for youth in a predominantly Latinx rural community in the U.S. The intervention incorporated multimodal creative activities into the social cognitive career theory-based healthcare career program. Participants (N = 75) were assessed for healthcare career self-efficacy, outcome expectations, and interests (pre-/post-intervention). Their healthcare career task self-efficacy and interests scores significantly increased overall. By race/ethnicity groups, however, only White students reported an increase in healthcare interests, and only students of color an increase in healthcare career task self-efficacy. This provides preliminary evidence for the effectiveness of the proposed intervention. Implications for services and research are discussed.

Intervention de carrière dans le domaine des soins de santé auprès des jeunes dans une communauté rurale à prédominance latine: Une étude pilote d'une approche créative La présente étude porte sur une intervention pilote destinée aux jeunes d'une communauté rurale à prédominance latine aux États-Unis. L'intervention a intégré des activités créatives multimodales dans le programme de carrière en soins de santé basé sur la théorie sociale cognitive des carrières. Les participant·e·s (N = 75) ont été évalué·e·s sur leur sentiment d'efficacité personnelle dans les soins, leurs attentes en matière de résultats et leurs intérêts (avant et après l'intervention). Les résultats du sentiment d'efficacité personnelle des tâches et des intérêts de leur carrière dans le domaine de la santé ont augmenté de manière significative dans l'ensemble. Toutefois, par groupe racial ou ethnique, seul·e·s les étudiant·e·s blancs ont signalé une augmentation de leurs intérêts pour les soins de santé, et seul·e·s les étudiant·e·s de couleur ont signalé une augmentation de leur sentiment d'efficacité personnelle dans les tâches liées aux soins de santé. Cela fournit des preuves préliminaires de l'efficacité de l'intervention proposée. Les implications pour les services et la recherche sont discutées.

Intervención en la carrera de atención médica con jóvenes en una comunidad rural predominantemente latina: un estudio piloto de un enfoque creativo El presente estudio analiza una intervención piloto para jóvenes en una comunidad rural predominantemente latina en los EE. UU. La intervención incorporó actividades creativas multimodales en el programa de carrera de atención médica basado en el enfoque socio-cognitivo de la carrera. Se evaluó a los participantes (N = 75) en cuanto a la percepción de la autoeficacia para la carrera sanitaria, las expectativas de resultados y los intereses (antes y después de la intervención). Sus puntuaciones de percepción de autoeficacia e intereses en las tareas de la carrera sanitaria aumentaron significativamente en general. Sin embargo, por grupos de raza / etnia, solo los estudiantes blancos mostraron un aumento en los intereses relacionados con la atención médica, y solo en los estudiantes de color se observó un incremento en la percepción de autoeficacia para las tareas profesionales de la salud. Esto proporciona evidencia preliminar de la efectividad de la intervención propuesta. Se discuten las implicaciones para los servicios y la investigación.

Online Behavioral Screener with Tailored Obesity Prevention Messages: Application to a Pediatric Clinical Setting.

Obesity prevention involves promoting healthy eating and physical activity across all children. Can we leverage technology to feasibly survey children's health behaviors and deliver theory-based and user-tailored messages for brief clinical encounters? We assessed the acceptability and utility of an online pediatric-adapted liking survey (PALS) and tailored messages among children receiving non-urgent care in a pediatric emergency department (PED). Two hundred and forty-five children (average age = 10 years, racially/ethnically diverse, 34% overweight/obese from measured indices, 25% of families reporting food insecurity) and their parents/caregivers participated. Each reported the child's activity and behaviors using the online PALS and received two to three messages tailored to the responses (aligned with elaboration likelihood and transtheoretical models) to motivate behavioral improvements or reinforce healthy behaviors. Most children and parents (>90%) agreed the PALS was easy to complete, encouraging thought about their own/child's behaviors. The child's PALS responses appeared reasonable (fair-to-good child-parent intraclass correlations). Most children and parents (≥75%) reported the tailored messages to be helpful and favorable for improving or maintaining the targeted behavior. Neither message type (motivating/reinforcing) nor favorability responses varied significantly by the child's weight or family's food security status. In summary, children and parents found the PALS with tailored messages acceptable and useful. The message types and responses could help focus brief clinical encounters.

Insights from healthcare academics on facilitating interprofessional education activities.

Facilitators are of paramount importance to the success of interprofessional education (IPE) activities; hence, it is crucial to explore their perspectives and experiences in delivering IPE in Qatar. Using an exploratory case study approach, semi-structured interviews were conducted, in 2018, among faculty members, who had facilitated at least one IPE activity in Qatar, from healthcare professional education programs at Qatar University Colleges of Pharmacy, Medicine, and Health Sciences, Weill Cornell Medicine in Qatar, the University of Calgary in Qatar, and the College of North Atlantic. Interviews were recorded and transcribed verbatim. Inductive thematic content analysis was implemented. Twenty-one interviews were conducted with the following professions represented: medicine (n = 6), pharmacy (n = 5), nursing (n = 4), biomedical science (n = 3), respiratory theory (n = 2) and public health (n = 1). Four main themes emerged from the interviews: drivers to facilitator involvement that included interest and commitment to IPE and awareness of collaborative practice benefits; facilitator participation which was based on facilitator attributes and preparedness and readiness for IPE facilitation; the organizational support in terms of dedicated structure for IPE and IPE design and delivery and; student participation in terms of group dynamics and student engagement. Some key recommendations include having a dedicated unit for IPE, scheduling protected time for IPE, and organizing facilitators' training and debriefing workshops. The facilitators valued and appreciated IPE in preparing students for future collaborative practice. These findings can inform the development of quality and sustainable IPE activities in the future.

Critical appraisal of tobacco dependence treatment guidelines.

Background Tobacco use is a leading preventable cause of morbidity and mortality globally. Clinical practice guidelines for the treatment of tobacco use dependence are of varied scope and quality, making it challenging for users to select and apply recommendations. Objective The study objective is to identify and critically appraise the quality of existing clinical practice guidelines for tobacco cessation. Setting The study occurred between collaborative academic institutions located in Qatar and New Zealand. Methods A systematic literature search was performed for the period 2006-2018 through the following databases: PubMed, EMBASE, CINAHL, ISI Web of Science, Scopus, National Guideline Clearing House, Campbell Library, Health System Evidence, Joanna Briggs Institute Evidence-Based Practice Database, Academic Search Complete, ProQuest, PROSPERO, and Google Scholar. Relevant professional societies' and health agencies' websites were also searched. Two reviewers independently extracted and assessed guidelines' quality using Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. Main outcome measure Standardized domain scores according to the AGREE II instrument. Results 7741 hits were identified. After removing duplicates and screening, 24 guidelines were included. Highest guideline quality was for National Institute for Health and Care Excellence (NICE) guideline with an overall ranking score of 87.56% and least quality was for Japanese Circulation Society Joint Working Group with an overall score of 29.34%. Domain 4 of AGREE II (clarity of presentation) had the highest average quality score (70.95%), while the lowest average quality scores were for Domain 2 (Rigour of Development) (50.21%) and Domain 5 (Applicability) (45.05%). Conclusion Seven guidelines were judged to be of high quality (overall score of ≥ 70%). Future guidelines for tobacco dependence treatment should use rigorous methods of development and provide applicable recommendations.

Silent Dyspnea: Spontaneous Pneumomediastinum in a Heroin User.

Spontaneous pneumomediastinum (SPM) is a relatively rare presentation that often follows a benign clinical course. It is mainly triggered by underlying bronchial asthma, respiratory tract infections, strenuous activities, or illicit drug use. We present a case of an isolated primary pneumomediastinum where the patient was a 24-year-old man with underlying bronchial asthma who presented with acute onset of shortness of breath and pleuritic chest pain following snorting of an opioid-heroin. Although the clinical exam and chest radiograph were both unremarkable, the multi-detector computed tomography of the chest revealed an isolated pneumomediastinum. The patient was managed conservatively in accordance with existing evidence as SPM is known for its spontaneous recovery.

The Neuroanatomical Ultrastructure and Function of a Biological Ring Attractor.

Neural representations of head direction (HD) have been discovered in many species. Theoretical work has proposed that the dynamics associated with these representations are generated, maintained, and updated by recurrent network structures called ring attractors. We evaluated this theorized structure-function relationship by performing electron-microscopy-based circuit reconstruction and RNA profiling of identified cell types in the HD system of Drosophila melanogaster. We identified motifs that have been hypothesized to maintain the HD representation in darkness, update it when the animal turns, and tether it to visual cues. Functional studies provided support for the proposed roles of individual excitatory or inhibitory circuit elements in shaping activity. We also discovered recurrent connections between neuronal arbors with mixed pre- and postsynaptic specializations. Our results confirm that the Drosophila HD network contains the core components of a ring attractor while also revealing unpredicted structural features that might enhance the network's computational power.