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1.
Eur Radiol ; 33(11): 8112-8121, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37209125

ABSTRACT

OBJECTIVES: To analyze the performance of deep learning in isodense/obscure masses in dense breasts. To build and validate a deep learning (DL) model using core radiology principles and analyze its performance in isodense/obscure masses. To show performance on screening mammography as well as diagnostic mammography distribution. METHODS: This was a retrospective, single-institution, multi-centre study with external validation. For model building, we took a 3-pronged approach. First, we explicitly taught the network to learn features other than density differences: such as spiculations and architectural distortion. Second, we used the opposite breast to enable the detection of asymmetries. Third, we systematically enhanced each image by piece-wise-linear transformation. We tested the network on a diagnostic mammography dataset (2569 images with 243 cancers, January to June 2018) and a screening mammography dataset (2146 images with 59 cancers, patient recruitment from January to April 2021) from a different centre (external validation). RESULTS: When trained with our proposed technique (and compared with baseline network), sensitivity for malignancy increased from 82.7 to 84.7% at 0.2 False positives per image (FPI) in the diagnostic mammography dataset, 67.9 to 73.8% in the subset of patients with dense breasts, 74.6 to 85.3 in the subset of patients with isodense/obscure cancers and 84.9 to 88.7 in an external validation test set with a screening mammography distribution. We showed that our sensitivity exceeded currently reported values (0.90 at 0.2 FPI) on a public benchmark dataset (INBreast). CONCLUSION: Modelling traditional mammographic teaching into a DL framework can help improve cancer detection accuracy in dense breasts. CLINICAL RELEVANCE STATEMENT: Incorporating medical knowledge into neural network design can help us overcome some limitations associated with specific modalities. In this paper, we show how one such deep neural network can help improve performance on mammographically dense breasts. KEY POINTS: • Although state-of-the-art deep learning networks achieve good results in cancer detection in mammography in general, isodense, obscure masses and mammographically dense breasts posed a challenge to deep learning networks. • Collaborative network design and incorporation of traditional radiology teaching into the deep learning approach helped mitigate the problem. • The accuracy of deep learning networks may be translatable to different patient distributions. We showed the results of our network on screening as well as diagnostic mammography datasets.


Subject(s)
Breast Neoplasms , Deep Learning , Humans , Female , Mammography/methods , Breast Density , Retrospective Studies , Breast Neoplasms/diagnostic imaging , Early Detection of Cancer
2.
Mol Biol Rep ; 50(3): 2685-2700, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36534236

ABSTRACT

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , B7-H1 Antigen , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor , Immunotherapy/methods
3.
J Appl Biomech ; 39(5): 284-293, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37348849

ABSTRACT

In this review, we elaborate on how musculoskeletal (MSK) modeling combined with dynamic movement simulation is gradually evolving from a research tool to a promising in silico tool to assist medical doctors and physical therapists in decision making by providing parameters relating to dynamic MSK function and loading. This review primarily focuses on our own and related work to illustrate the framework and the interpretation of MSK model-based parameters in patients with 3 different conditions, that is, degenerative joint disease, cerebral palsy, and adult spinal deformities. By selecting these 3 clinical applications, we also aim to demonstrate the differing levels of clinical readiness of the different simulation frameworks introducing in silico model-based biomarkers of motor function to inform MSK rehabilitation and treatment, with the application for adult spinal deformities being the most recent of the 3. Based on these applications, barriers to clinical integration and positioning of these in silico technologies within standard clinical practice are discussed in the light of specific challenges related to model assumptions, required level of complexity and personalization, and clinical implementation.

4.
BMC Med Educ ; 22(1): 689, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36151552

ABSTRACT

BACKGROUND: It is now a General Medical Council requirement to incorporate education for sustainable healthcare (ESH) into medical curricula. To date, research has focussed on the perspectives of educators and which sustainable healthcare topics to include in teaching. Therefore, due to this gap in the literature, we have investigated the perspectives of medical students in the UK regarding current and future incorporation of ESH in medical education. METHODS: A survey was circulated to 851 clinical year medical students and students intercalating after completing at least one clinical year in a London University. The anonymous survey consisted of sections on the environmental impact, current teaching and future teaching of ESH. RESULTS: One hundred sixty-three students completed the survey. 93% of participants believed that climate change is a concern in current society, and only 1.8% thought they have been formally taught what sustainable healthcare is. No participants strongly agreed, and only 5 participants (3.1%) agreed, that they would feel confident in answering exam questions on this topic, with 89% agreeing that more ESH is needed. 60% believe that future teaching should be incorporated in both preclinical and clinical years, with 31% of participants preferring online modules as the method of teaching. CONCLUSION: Our study has stressed the lack of current sustainable healthcare teaching in the medical curriculum. There is student demand for ESH, however, uncertainty remains regarding who is best placed to facilitate ESH, how it should be delivered, and whether there is a gender discrepancy regarding sustainable healthcare importance, emphasising the need to close the gap between educational rhetoric and action.


Subject(s)
Education, Medical, Undergraduate , Education, Medical , Students, Medical , Curriculum , Delivery of Health Care , Humans , Schools, Medical , United Kingdom
5.
J Appl Biomech ; 37(5): 432-439, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34504045

ABSTRACT

Knee abduction/adduction moment and knee internal rotation moment are known surrogate measures of anterior cruciate ligament (ACL) load during tasks like sidestepping and single-leg landing. Previous experimental literature has shown that a variety of kinematic strategies are associated or correlated with ACL injury risk; however, the optimal kinematic strategies needed to reduce peak knee moments and ACL injury are not well understood. To understand the complex, multifaceted kinematic factors underpinning ACL injury risk and to optimize kinematics to prevent the ACL injury, a musculoskeletal modeling and simulation experimental design was used. A 14-segment, 37-degree-of-freedom, dynamically consistent skeletal model driven by force/torque actuators was used to simulate whole-body single-leg jump landing kinematics. Using the residual reduction algorithm in OpenSim, whole-body kinematics were optimized to reduce the peak knee abduction/adduction and internal/external rotation moments simultaneously. This optimization was repeated across 30 single-leg jump landing trials from 10 participants. The general optimal kinematic strategy was to bring the knee to a more neutral alignment in the transverse plane and frontal plane (featured by reduced hip adduction angle and increased knee adduction angle). This optimized whole-body kinematic strategy significantly reduced the peak knee abduction/adduction and internal rotation moments, transferring most of the knee load to the hip.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Injuries/prevention & control , Biomechanical Phenomena , Humans , Knee , Knee Joint , Leg
7.
J Contemp Dent Pract ; 19(9): 1100-1104, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30287711

ABSTRACT

AIM: The placement of composite in teeth is not an easy task and it poses many challenges. Microleakage is one of the factors that affects the success of any composite restoration. It influences the longevity of dental restorations. The present study was aimed to evaluate and compare microleakage of two restorative composites resins in class II cavities using confocal laser scanning microscopy (CLSM). MATERIALS AND METHODS: This was an in vitro study, which included 20 permanent mandibular first molar. On each tooth, 40 class II cavities were prepared with a carbide bur. The teeth were then randomly divided into two groups of 10 each. Group I included teeth in which SonicFill Bulk Fill composite was used. Group II included teeth in which Tetric EvoCeram Bulk Fill composite was used. The microleakage was measured using confocal microscopy at 10* magnification in the fluorescent mode by a scoring system. RESULTS: Estimation was done at cervical and occlusal levels, wherein group I included 10 teeth which were restored with SonicFill Bulk Fill composite and group II included 10 teeth which were restored with Tetric EvoCeram Bulk Fill composite. Microleakage was quantified on scoring basis, which was consecutively based on the dye penetration at different levels. Data thus obtained statistically revealed that microleakage was comparatively more in group II as compared with group I. In addition, it was somewhat similar on both cervical as well as occlusal regions. The difference was significant (p = 0.05). Comparison was also done at cervical and occlusal levels using Wilcoxon signed-rank test, which showed significant levels of differences (p > 0.05). CONCLUSION: There is more microleakage in Tetric EvoCeram Bulk Fill composite as compared with SonicFill Bulk Fill composite. CLINICAL SIGNIFICANCE: No material seems to totally eliminate microleakage in class II situations with gingival margin ended in dentine. However, CLSM is a useful tool in microleakage evaluation that could be used successfully to estimate the severity of microbial penetrations and material of choice as well.


Subject(s)
Acrylic Resins , Composite Resins , Dental Caries , Dental Cavity Preparation/methods , Dental Leakage , Dental Restoration, Permanent/methods , Microscopy, Confocal , Polyurethanes , Humans , In Vitro Techniques , Mandible , Molar
8.
Am J Perinatol ; 34(1): 8-13, 2017 01.
Article in English | MEDLINE | ID: mdl-27182997

ABSTRACT

Objective We aimed to evaluate variability in Apgar score (AS) assignment among health care providers (HCPs) and to evaluate whether a simple clarification improves accuracy and consistency of AS assignment. Study Design An electronic questionnaire survey was provided to pediatric residents, nurse practitioners, neonatal fellows, and faculty in level III neonatal intensive care unit and major academic centers in the United State to assign AS for three clinical scenarios. Next, we provided a simple clarification on various components of AS. After review of clarification, responders were asked to provide AS for the same scenarios. We also sought the opinion of responders on the subjectivity of five components of AS. Results A total of 107 responses were collected. Correct assignment before and after clarification improved significantly: heart rate (78 vs. 90%, p = 0.02), reflex (63 vs.75%, p = 0.06), and breathing (82 vs. 96%, p = 0.003). Correct scoring for color and tone were 86 and 67%, respectively. Interobserver agreement improved significantly after clarification. Conclusion There was variability among HCPs for AS assignment, with improvement in correct response as well as consistency after a simple clarification. Availability of this clarification, along with the AS table in delivery room, will improve the correct assignment and consistency of AS for high-risk infants.


Subject(s)
Apgar Score , Fellowships and Scholarships , Internship and Residency , Neonatology/education , Observer Variation , Pediatrics/education , Cyanosis , Faculty, Medical , Heart Rate , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Muscle Tonus , Nurse Practitioners , Reflex , Respiration
10.
Am J Perinatol ; 32(9): 839-44, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25607222

ABSTRACT

OBJECTIVE: This study aims to examine the association between measures of hypercapnia and fluctuation in Pco 2 and severe intraventricular hemorrhage (IVH) and to evaluate the prevalence of hypercapnia, hypocapnia, and fluctuations in Pco 2 in the initial 72 hours of life among premature infants. STUDY DESIGN: Retrospective study of premature infants with birth weight < 1,250 g, who were receiving some respiratory support. All blood gases obtained in the first 3 days of life were collected. Univariate and multivariate analyses were performed to assess the association of hypercapnia, and fluctuations in Pco 2 with severe IVH. RESULT: Our cohort included 285 patients, of whom 84% were intubated. Only 20% patients had all blood gases in the normocapnia range; 9% had at least 1 gas with hypercapnia; 51% had at least 1 gas with hypocapnia, and 20% patients had both hypercapnia and hypocapnia at different times. Infants with severe IVH (n = 41) had significantly higher peak Pco 2 and greater fluctuations in Pco 2 within a short interval, compared with those without severe IVH (n = 227). After controlling for gestational age, gender, antenatal steroid exposure, presence of hypercapnia, and Apgar score at 5 minutes, fluctuation in Pco 2 remained significantly associated with severe IVH. CONCLUSION: Fluctuations in Pco 2 within a short period may be more significantly associated with severe IVH than the mere presence of hypercapnia.


Subject(s)
Carbon Dioxide/blood , Cerebral Hemorrhage/epidemiology , Hypercapnia/blood , Hypocapnia/blood , Infant, Extremely Premature/blood , Infant, Very Low Birth Weight/blood , Apgar Score , Birth Weight , Blood Gas Analysis , Female , Gestational Age , Humans , Infant, Newborn , Logistic Models , Male , Retrospective Studies
12.
Pharm Nanotechnol ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468532

ABSTRACT

Lung cancer, a leading cause of cancer-related deaths globally, is gaining research interest more than ever before. Owing to the burden of pathogenesis on the quality of life of patients and subsequently the healthcare system, research efforts focus on its management and amelioration. In an effort to improve bioavailability, enhance stability, minimize adverse effects and reduce the incidence of resistance, nanotechnological platforms have been harnessed for drug delivery and improving treatment outcomes. Lipid nanoparticles, in particular, offer an interesting clinical opportunity with respect to the delivery of a variety of agents. These include synthetic chemotherapeutic agents, immunotherapeutic molecules, as well as phytoconstituents with promising anticancer benefits. In addition to this, these systems are being studied for their usage in conjunction with other treatment strategies. However, their applications remain limited owing to a number of challenges, chiefly clinical translation. There is a need to address the scalability of such technologies, in order to improve accessibility. The authors aim to offer a comprehensive understanding of the evolution of lipid nanoparticles and their application in lung cancer, the interplay of disease pathways and their mechanism of action and the potential for delivery of a variety of agents. Additionally, a discussion with respect to results from preclinical studies has also been provided. The authors have also provided a well-rounded insight into the limitations and future perspectives. While the possibilities are endless, there is a need to undertake focused research to expedite clinical translation and offer avenues for wider applications in disease management.

13.
Eur J Pharm Biopharm ; : 114508, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39306201

ABSTRACT

The field of Machine Learning (ML) has garnered significant attention, particularly in healthcare for predicting disease severity. Recently, the pharmaceutical sector has also adopted ML techniques in various stages of drug development. Tablets are the most common pharmaceutical formulations, with their efficacy influenced by the physicochemical properties of active ingredients, in-process parameters, and formulation components. In this study, we developed ML-based prediction models for disintegration time, friability, and water absorption ratio of fast disintegration tablets. The model development process included data visualization, pre-processing, splitting, ML model creation, and evaluation. We evaluated the models using root mean square error (RMSE) and R-squared score (R2). After hyperparameter tuning and cross-validation, the voting regressor model demonstrated the best performance for predicting disintegration time (RMSE: 21.99, R2: 0.76), surpassing previously reported models. The random forest regressor achieved the best results for friability prediction (RMSE: 0.142, R2: 0.7), and the K-nearest neighbor (KNN) regressor excelled in predicting the water absorption ratio (RMSE: 10.07, R2: 0.94). Notably, predicting friability and water absorption ratio using ML models is unprecedented in the literature. The developed models were deployed in a web app for easy access by anyone. These ML models can significantly enhance the tablet development phase by minimizing experimental iterations and material usage, thereby reducing costs and saving time.

14.
Curr Probl Cardiol ; 49(1 Pt B): 102081, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37716543

ABSTRACT

The metabolism of lipoproteins, which regulate the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, the authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by 2 biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained in different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.


Subject(s)
Calcium , Ventricular Remodeling , Humans , Lipid Metabolism/physiology , Homeostasis/physiology , Cholesterol
15.
J Am Acad Psychiatry Law ; 52(3): 304-310, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39054039

ABSTRACT

Forensic psychiatry fellowship programs recruit applicants through a nonstandardized process that differs by program. Although there are deadlines, informal guidance, and more recent communication guidelines, perceived differences in recruitment practices persist between geographic regions, small and large programs, and newer and more well-established programs. In the wake of a survey of fellowship applicants that found mixed opinions surrounding the application process, U.S. forensic fellowship directors undertook a mixed method quantitative-qualitative survey of their colleagues to assess interest in a match as a potential improvement and factors influencing that interest (e.g., program size, age, and unfilled positions). With responses from all 46 active U.S. programs, results indicated broad support for principles of fairness, transparency, and minimizing pressure on applicants, with an almost perfectly divided interest in a match. Respondents supported the use of a centralized database to standardize the application process and favored certain exceptions for internal applicants. Hypotheses about the reasons underlying program directors' attitudes toward a match did not yield significant results, with only the size of a program approaching significance. This novel comprehensive survey of forensic fellowship directors offers a model for assessing and monitoring the evolution of application processes for medical subspecialties interested in expanding and improving their recruitment.


Subject(s)
Fellowships and Scholarships , Forensic Psychiatry , Humans , Forensic Psychiatry/education , United States , Surveys and Questionnaires , Personnel Selection , Attitude of Health Personnel , Female , Physician Executives , Male , Adult
16.
Med Oncol ; 41(11): 249, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316239

ABSTRACT

The incidence of lung cancer continues to grow globally, contributing to an ever-increasing load on healthcare systems. Emerging evidence has indicated lowered efficacy of conventional treatment strategies, such as chemotherapy, surgical interventions and radiotherapy, prompting the need for exploring alternative interventions. A growing focus on immunotherapy and the development of personalized medicine has paved the way for vaccine-based delivery in lung cancer. With various prominent targets such as CD8+T cells and PD-L1, immune-targeted, anti-cancer vaccines have been evaluated in both, pre-clinical and clinical settings, to improve therapeutic outcomes. However, there are a number of challenges that must be addressed, including the scalability of such delivery systems, heterogeneity of lung cancers, and long-term safety as well as efficacy. In addition to this, natural compounds, in combination with immunotherapy, have gained considerable research interest in recent times. This makes it necessary to explore their role in synergism with immune-targeted agents. The authors of this review aim to offer an overview of recent advances in our understanding of lung cancer pathogenesis, detection and management strategies, and the emergence of immunotherapy with a special focus on vaccine delivery. This finding is supported with evidence from testing in non-human and human models, showcasing promising results. Prospects for phytotherapy have also been discussed, in order to combat some pitfalls and limitations. Finally, the future perspectives of vaccine usage in lung cancer management have also been discussed, to offer a holistic perspective to readers, and to prompt further research in the domain.


Subject(s)
Cancer Vaccines , Immunotherapy , Lung Neoplasms , Humans , Lung Neoplasms/therapy , Cancer Vaccines/therapeutic use , Immunotherapy/methods , Animals
17.
Ageing Res Rev ; 89: 101979, 2023 08.
Article in English | MEDLINE | ID: mdl-37328112

ABSTRACT

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by several pathological features. In AD and PD, there is an abnormal accumulation of toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, increased astrocyte activation, and perhaps a state of insulin resistance. Epidemiological evidence has revealed a link between AD/PD and type 2 diabetes mellitus, with these disorders sharing some pathological commonalities. Such a link has opened up a promising avenue for repurposing antidiabetic agents in the treatment of neurodegenerative disorders. A successful therapeutic strategy for AD/PD would likely require a single or several agents which target the separate pathological processes in the disease. Targeting cerebral insulin signalling produces numerous neuroprotective effects in preclinical AD/PD brain models. Clinical trials have shown the promise of approved diabetic compounds in improving motor symptoms of PD and preventing neurodegenerative decline, with numerous further phase II trials and phase III trials underway in AD and PD populations. Alongside insulin signalling, targeting incretin receptors in the brain represents one of the most promising strategies for repurposing currently available agents for the treatment of AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists have displayed impressive clinical potential in preclinical and early clinical studies. In AD the GLP-1 receptor agonist, liraglutide, has been demonstrated to improve cerebral glucose metabolism and functional connectivity in small-scale pilot trials. Whilst in PD, the GLP-1 receptor agonist exenatide is effective in restoring motor function and cognition. Targeting brain incretin receptors reduces inflammation, inhibits apoptosis, prevents toxic protein aggregation, enhances long-term potentiation and autophagy as well as restores dysfunctional insulin signalling. Support is also increasing for the use of additional approved diabetic treatments, including intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear receptor γ agonists, amylin analogs, and protein tyrosine phosphatase 1B inhibitors which are in the investigation for deployment in PD and AD treatment. As such, we provide a comprehensive review of several promising anti-diabetic agents for the treatment of AD and PD.


Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Neurodegenerative Diseases , Neuroprotective Agents , Parkinson Disease , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Incretins/therapeutic use , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/therapeutic use , Neurodegenerative Diseases/metabolism , Insulin/therapeutic use , Inflammation/drug therapy , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use
18.
Lancet Planet Health ; 7(1): e64-e67, 2023 01.
Article in English | MEDLINE | ID: mdl-36608951

ABSTRACT

In the context of accelerating concern regarding the climate and ecological crisis and the recognition of this crisis as a health threat, there is growing motivation among the health-care community to reduce the negative environmental impact of health care. Globally, the health-care sector is estimated to be the 5th largest carbon emitter. A health system that is socially, environmentally, and financially sustainable requires clinical leadership, yet few health-care workers possess the conceptual framework or practical skills for creating new models of care. Clinicians can protect planetary health as a core part of professional practice by integrating triple bottom line measures into quality improvement or quality management practices. Initial efforts to integrate sustainability into quality improvement teaching and training have been shown to transform learners' interest in quality improvement and environmental sustainability. Embedding sustainability principles and techniques into established quality improvement education and practice can operationalise planetary health, building the skills necessary for health-care system transformation at the speed and scale required.


Subject(s)
Delivery of Health Care , Health Personnel , Humans , Curriculum , Environment , Leadership
19.
Biomedicines ; 11(1)2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36672729

ABSTRACT

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, there is a need to explore nanodelivery of this agent, owing to its poor solubility, which in turn may impact its bioavailability. This review aims to offer an overview of the occurrence and pathogenesis of B cell malignancies with a special focus on the inflammatory pathways involved, the mechanism of actions of resveratrol and its pharmacokinetic profile, results from pre-clinical and clinical studies, as well as an overview of the marketed formulations. The authors have also presented their opinion on the various challenges associated with the clinical development of resveratrol and future perspectives regarding therapeutic applications of this agent.

20.
Toxicol Res (Camb) ; 12(5): 716-740, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37915472

ABSTRACT

Introduction: Apoptosis, necrosis, and cancer necrosis factor (TNF-a) are all impacted by the nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) at nano-biointerfaces. The creation of multi-functional nanoparticles has had a considerable impact on the transport of drugs and genes, nanotheranostics (in-vivo imaging, concurrent diagnostics), interventions for external healing, the creation of nano-bio interfaces, and the instigation of desired changes in nanotherapeutics. Objectives: The quantitative structure-activity relationships, chemical transformations, biological interactions as well as toxicological analyses are considered as main objectives. Discrete dimensions of SCoNPs-cell interaction interfaces, their characteristic physical features (size, shape, shell structure, and surface chemistry), impact on cell proliferation and differentiation are the key factors responsible for nanotoxicity. Methods: The development of multi-functional nanoparticles has been significant in drug/gene delivery, nanotheranostics (in-vivo imaging, coinciding diagnostics), and external healing interventions, designing a nano-bio interface, as well as inciting desired alterations in nanotherapeutics. Every so often, the cellular uptake of multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoONPs) influences cellular mechanics and initiates numerous repercussions (oxidative stress, DNA damage, cytogenotoxicity, and chromosomal damage) in pathways, including the generation of dysregulating factors involved in biochemical transformations. Results: The concerns and influences of multifunctional SCoNPs on different cell mechanisms (mitochondria impermeability, hydrolysis of ATP, the concentration of Ca2+, impaired calcium clearance, defective autophagy, apoptosis, and necrosis), and interlinked properties (adhesion, motility, and internalization dynamics, role in toxicity, surface hydrophilic and hydrophobicity, biokinetics and biomimetic behaviors of biochemical reactions) have also been summarized. SCoONPs have received a lot of interest among the nanocarriers family because of its advantageous qualities such as biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. Conclusion: Various applications, such as bio-imaging, cell labeling, gene delivery, enhanced chemical stability, and increased biocompatibility, concerning apoptosis, necrosis, and nano-bio interfaces, along with suitable examples. In this analysis, the multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoNPs) intricacies (cytogenotoxicity, clastogenicity, and immunomodulatory), nanotoxicity, and associated repercussions have been highlighted and explained.

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