Development of Fluorescent nanoparticles “Quantum Dots” for biomedical application

Background: Quantum dots (QDs) have emerged as one of the most exciting fluorescent nanoparticles with a potential for diagnostic and therapeutic application in the field of nanomedicine. The aim of this study was to synthesize water soluble QDs; bio-conjugating these QDs with RGD peptides prior to linking the QD-conjugated peptide to cancer cells with the aim to study cytotoxicity and assess its feasibility for in vivo studies. Methods: Water soluble Cadmium Telluride (CdTe) QDs were synthesized by the reaction of cadmium chloride with sodium tellurite in the presence of buffer solution of Mercaptosuccinic acid (MSA) as a capping ligand. Water soluble red emitting QDs thus obtained were characterized using spectrophotometric analysis. These QDs revealed a wide absorption spectrum with an excitonic absorption peak of 380nm and a narrow symmetrical emission spectrum of 630nm. The size and pattern of these QDs were studied using Transmission Electron Microscopy (TEM). These nanocrystals revealed their configuration in the form of isolated crystals or clusters measuring from 5-10nm in diameter. X-ray microanalysis combined with TEM permitted analysis of the elemental configuration of these QDs. These CdTe QDs were subsequently bound to HT 29 colon cancer cells to study the interaction of QDs in vitro. As colon cancer cells over-express integrins, QDs were conjugated with RGD (Lysine) and RGD (Cysteine) peptides for the purpose of active binding with HT29 colon cancer cells. The conjugated QDs were applied to colorectal cancer cells to assess their affinity to cellular adhesion molecules. The toxicity of naked and conjugated QDs was also assessed by analyzing cell survival and cell death after exposure to C2C12 mouse skeletal muscle cells. In vivo experiment using Sprague 5 Dawley (SD) rat established feasibility of biodistribution studies with a small dose of 10μg/ml. Results: These water soluble fluorescent CdTe nanocrystals were synthesized using relatively stable precursors. It was possible to demonstrate binding of these red emitting QDs to the HT29 colon cancer cells in vitro. Significant and stable binding was noted after QDs were conjugated with RGD peptides. Toxicity assay evaluation studies suggested that both nonconjugated and conjugated QDs were nontoxic to C2C12 mouse skeletal muscle cells at a concentration of 50 μg /ml indicating that they are less toxic to normal cells, and are safe to be applied to in vivo models. Further in vivo experimentation in SD rats established feasibility for imaging sentinel lymph nodes following interdigital web space injection of QDs. Conclusions: RGD-conjugated QDs can selectively target HT29 colorectal cancer cells with low toxicity to normal muscle cells offering a potential novel detection strategy for colorectal cancer. This property can be explored for early diagnostic and therapeutic purpose by selectively targeting cancer cells. Further studies are required in an in vivo model to analyze systemic biodistribution and toxicity studies

Integrating artificial intelligence into an ophthalmologist’s workflow: obstacles and opportunities

Introduction: Demand in clinical services within the field of ophthalmology is predicted to rise over the future years. Artificial intelligence, in particular, machine learning-based systems, have demonstrated significant potential in optimizing medical diagnostics, predictive analysis, and management of clinical conditions. Ophthalmology has been at the forefront of this digital revolution, setting precedents for integration of these systems into clinical workflows. Areas covered: This review discusses integration of machine learning tools within ophthalmology clinical practices. We discuss key issues around ethical consideration, regulation, and clinical governance. We also highlight challenges associated with clinical adoption, sustainability, and discuss the importance of interoperability. Expert opinion: Clinical integration is considered one of the most challenging stages within the implementation process. Successful integration necessitates a collaborative approach from multiple stakeholders around a structured governance framework, with emphasis on standardization across healthcare providers and equipment and software developers

AI as a Medical Device for Ophthalmic Imaging in Europe, Australia, and the United States: Protocol for a Systematic Scoping Review of Regulated Devices

\ua9 2024 JMIR Publications Inc.. All rights reserved.Background: Artificial intelligence as a medical device (AIaMD) has the potential to transform many aspects of ophthalmic care, such as improving accuracy and speed of diagnosis, addressing capacity issues in high-volume areas such as screening, and detecting novel biomarkers of systemic disease in the eye (oculomics). In order to ensure that such tools are safe for the target population and achieve their intended purpose, it is important that these AIaMD have adequate clinical evaluation to support any regulatory decision. Currently, the evidential requirements for regulatory approval are less clear for AIaMD compared to more established interventions such as drugs or medical devices. There is therefore value in understanding the level of evidence that underpins AIaMD currently on the market, as a step toward identifying what the best practices might be in this area. In this systematic scoping review, we will focus on AIaMD that contributes to clinical decision-making (relating to screening, diagnosis, prognosis, and treatment) in the context of ophthalmic imaging.Objective: This study aims to identify regulator-approved AIaMD for ophthalmic imaging in Europe, Australia, and the United States; report the characteristics of these devices and their regulatory approvals; and report the available evidence underpinning these AIaMD.Methods: The Food and Drug Administration (United States), the Australian Register of Therapeutic Goods (Australia), the Medicines and Healthcare products Regulatory Agency (United Kingdom), and the European Database on Medical Devices (European Union) regulatory databases will be searched for ophthalmic imaging AIaMD through a snowballing approach. PubMed and clinical trial registries will be systematically searched, and manufacturers will be directly contacted for studies investigating the effectiveness of eligible AIaMD. Preliminary regulatory database searches, evidence searches, screening, data extraction, and methodological quality assessment will be undertaken by 2 independent review authors and arbitrated by a third at each stage of the process.Results: Preliminary searches were conducted in February 2023. Data extraction, data synthesis, and assessment of methodological quality commenced in October 2023. The review is on track to be completed and submitted for peer review by April 2024.Conclusions: This systematic review will provide greater clarity on ophthalmic imaging AIaMD that have achieved regulatory approval as well as the evidence that underpins them. This should help adopters understand the range of tools available and whether they can be safely incorporated into their clinical workflow, and it should also support developers in navigating regulatory approval more efficiently

AI as a Medical Device for Ophthalmic Imaging in Europe, Australia, and the United States:Protocol for a Systematic Scoping Review of Regulated Devices

BACKGROUND: Artificial intelligence as a medical device (AIaMD) has the potential to transform many aspects of ophthalmic care, such as improving accuracy and speed of diagnosis, addressing capacity issues in high-volume areas such as screening, and detecting novel biomarkers of systemic disease in the eye (oculomics). In order to ensure that such tools are safe for the target population and achieve their intended purpose, it is important that these AIaMD have adequate clinical evaluation to support any regulatory decision. Currently, the evidential requirements for regulatory approval are less clear for AIaMD compared to more established interventions such as drugs or medical devices. There is therefore value in understanding the level of evidence that underpins AIaMD currently on the market, as a step toward identifying what the best practices might be in this area. In this systematic scoping review, we will focus on AIaMD that contributes to clinical decision-making (relating to screening, diagnosis, prognosis, and treatment) in the context of ophthalmic imaging.OBJECTIVE: This study aims to identify regulator-approved AIaMD for ophthalmic imaging in Europe, Australia, and the United States; report the characteristics of these devices and their regulatory approvals; and report the available evidence underpinning these AIaMD.METHODS: The Food and Drug Administration (United States), the Australian Register of Therapeutic Goods (Australia), the Medicines and Healthcare products Regulatory Agency (United Kingdom), and the European Database on Medical Devices (European Union) regulatory databases will be searched for ophthalmic imaging AIaMD through a snowballing approach. PubMed and clinical trial registries will be systematically searched, and manufacturers will be directly contacted for studies investigating the effectiveness of eligible AIaMD. Preliminary regulatory database searches, evidence searches, screening, data extraction, and methodological quality assessment will be undertaken by 2 independent review authors and arbitrated by a third at each stage of the process.RESULTS: Preliminary searches were conducted in February 2023. Data extraction, data synthesis, and assessment of methodological quality commenced in October 2023. The review is on track to be completed and submitted for peer review by April 2024.CONCLUSIONS: This systematic review will provide greater clarity on ophthalmic imaging AIaMD that have achieved regulatory approval as well as the evidence that underpins them. This should help adopters understand the range of tools available and whether they can be safely incorporated into their clinical workflow, and it should also support developers in navigating regulatory approval more efficiently.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52602.</p

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Extended time range modeling of myelin growth

When some poorly water-soluble solid surfactants are contacted with water, several microstructures are observed as part of the dissolution process of the surfactants in water. One such microstructure called “myelin,” which is observed when a surfactant like phosphatidylcholine is contacted with water, is the subject of this paper. In this study we have used video microscopy to investigate myelin growth over a wide time range, namely 0.25–700 s, and found that existing models do not correctly express myelin growth over extended time ranges. When studied over a wide time range, the myelin growth was found to evolve over three distinct regimes, namely ballistic, diffusional, and subdiffusional regimes. The underlying growth models are physically explained and mathematically expressed. A relationship is derived between the width of myelin and the growth rate at long times. The estimated width of myelin is consistent with experiments.© Elsevie