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Purpose: To assess the management of patients with congenital nasolacrimal duct obstruction (CNLDO) in a paediatric population and review the long-term outcomes over a 5-year interval, with particular emphasis on the difference between patients with trisomy 21 and those without trisomy 21. Methods: This single-centre, retrospective, cross-sectional, case review study included patients suffering from CNLDO at Alder Hey Children's Hospital NHS foundation Trust. Patients were divided into two groups: Non-trisomy 21 and trisomy 21. Patients were followed-up for a 60-month interval. Patients aged <12 months at the time of surgery, patients with <60 months of follow-up data and patients with acquired nasolacrimal duct obstruction were excluded. The main outcome measures were discharge rates in patients undertaking primary intervention with syringe and probe (S&P), number of patients requiring further treatment with lacrimal intubation or dacryocystorhinostomy (DCR) and overall symptom-free periods post-treatment. Results: Ninety-three patients (142 eyes) were included. The mean number of surgical interventions was 1.53 ± 0.65. The mean interval between the 1st and 2nd intervention was 15.54 ± 16.33 months. There was a trend towards greater success rates non-trisomy 21 patients versus patients with trisomy 21 (p = 0.1352). The average symptom-free period after the final intervention was 44.31 ± 20.68 months, significantly longer in the non-trisomy 21 group compared to the trisomy 21 group (p = 0.0074). Conclusions: The overall success rate after primary S&P was 55.9%. Our results suggest that in trisomy 21 patients suffering from CNLDO, a one-stage intervention with primary monocanalicular intubation should be considered instead of sequential approach. [ABSTRACT FROM AUTHOR]

Kimura disease (KD) is a rare, chronic, inflammatory condition, predominantly found in male patients of Asian ethnicity. It typically presents between 50–60 years of age and usually with bilateral disease. Angiolymphoid hyperplasia with eosinophilia (ALHE) remains the main differential diagnosis, although histological analysis is essential in differentiating from other similarly presenting pathologies. In this case, we present an atypical case of unilateral orbital KD in a middle-aged, Caucasian, male gentleman and no evidence of regional lymphadenopathy along with a literature review of orbital KD and the differential diagnoses, histological features and management modalities available, adding to the sparse literature on the topic. At present, no recognised diagnostic criteria for KD are available, with histopathological analysis through incisional or excisional biopsy being the primary diagnostic method. Complete surgical excision with or without corticosteroid management remains the most common treatment modality although management is shifting to steroid-sparing immunomodulatory therapy. To the best of our knowledge, this is the first case to describe maintenance therapy of KD using mycophenolate mofetil. [ABSTRACT FROM AUTHOR]

We report a rare case of orbital inflammation complicating hemophagocytic lymphohistiocytosis (HLH) patient. HLH is a rare, life-threatening disorder characterized by uncontrolled activation of cytotoxic T lymphocytes, natural killer cells, and macrophages. A 37-year-old man known to have HLH, presented with a left periorbital swelling that was unsuccessfully treated as an orbital cellulitis, with intravenous antibiotics. A computed tomography (CT) scan of the orbits revealed inflammatory changes with no orbital collection or paranasal sinus disease. An orbital biopsy demonstrated lymphoplasmacytic infiltrations admixed with histiocytes. The patient deteriorated and was admitted to the intensive care unit. Ensuing blood results supported a diagnosis of HLH, and the patient responded well to subsequent immunosuppression. This case report highlights the importance of re-considering the diagnosis of orbital cellulitis in treatment resistant cases, particularly in the absence of sinus disease. To our knowledge, this is the third case of orbital inflammation associated with HLH patients. [ABSTRACT FROM AUTHOR]

Immune checkpoints refer to mechanisms entrusted with the modulation of immune responses in peripheral tissues and are required for minimising collateral damage. Immune checkpoint inhibitors (ICPi) work through numerous pathways, including the anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti-PD-1 (programmed cell death protein 1) and the PD-L1 (protein cell death protein-ligand-1) pathways. They are proving to be an exciting therapeutic avenue in the attempt to activate anti-tumour activity. Ipilimumab is a fully human monoclonal antibody working on the anti-CTLA-4 pathway, while nivolumab and pembrolizumab are humanised monoclonal IgG4 antibodies that work on the PD-1 pathway. Despite a growing body of research pertinent to these novel therapies, early indications show that they are limited by their side effect profile. Furthermore, their efficacy appears to be greater in cancers with a high mutational burden. We present two female patients with bilateral reactive dacryoadenitis secondary to ICPi therapy, a finding that to the best of our knowledge was not previously described in the literature. [ABSTRACT FROM AUTHOR]

A male patient in his early childhood presented to rheumatology with a hoarse voice and recurrent oral and cutaneous ulceration. Serological investigation revealed persistently elevated inflammatory markers. Despite compliance to treatment, flare-ups persisted, prompting the use of further treatment. An airway endoscopy revealed cystic changes to the left vocal cord. Referral to ophthalmology revealed multiple, waxy, skin-coloured, beaded papules on thickened, irregular eyelid margins with distichiasis, in keeping with moniliform blepharosis. Enrolment into the 100 000-genome project helped clinch the diagnosis of lipoid proteinosis. Although this case highlights the diagnostic power of genetics, it also sheds light on the importance of targeted clinical referral. When one considers the typical symptoms and signs of lipoid proteinosis, referral to a centre of rare diseases would have proven effective in not only avoiding polypharmacy but also reducing the psychological burden of several years of uncertainty must have had on our patient. [ABSTRACT FROM AUTHOR]

Large language models have received enormous attention recently with some studies demonstrating their potential clinical value, despite not being trained specifically for this domain. We aimed to investigate whether ChatGPT, a language model optimized for dialogue, can answer frequently asked questions about diabetes. We conducted a closed e-survey among employees of a large Danish diabetes center. The study design was inspired by the Turing test and non-inferiority trials. Our survey included ten questions with two answers each. One of these was written by a human expert, while the other was generated by ChatGPT. Participants had the task to identify the ChatGPT-generated answer. Data was analyzed at the question-level using logistic regression with robust variance estimation with clustering at participant level. In secondary analyses, we investigated the effect of participant characteristics on the outcome. A 55% non-inferiority margin was pre-defined based on precision simulations and had been published as part of the study protocol before data collection began. Among 311 invited individuals, 183 participated in the survey (59% response rate). 64% had heard of ChatGPT before, and 19% had tried it. Overall, participants could identify ChatGPT-generated answers 59.5% (95% CI: 57.0, 62.0) of the time, which was outside of the non-inferiority zone. Among participant characteristics, previous ChatGPT use had the strongest association with the outcome (odds ratio: 1.52 (1.16, 2.00), p = 0.003). Previous users answered 67.4% (61.7, 72.7) of the questions correctly, versus non-users' 57.6% (54.9, 60.3). Participants could distinguish between ChatGPT-generated and human-written answers somewhat better than flipping a fair coin, which was against our initial hypothesis. Rigorously planned studies are needed to elucidate the risks and benefits of integrating such technologies in routine clinical practice. [ABSTRACT FROM AUTHOR]

The recommended first-line therapy in type 2 diabetes (T2D) is lifestyle modification. In many patients, such interventions fail, and disease progresses inexorably to medication requirement. A potential reason for the failure of standard nutritional interventions is the use of generic dietary advice, with no personalisation to account for differences in the effect of food on blood glucose between different individuals. Another is the lack of instant feedback on the impact of dietary modification on glycaemic control, which supports sustained behaviour change. The use of continuous glucose monitoring (CGM) may help address both these shortcomings. We conducted an observational study to explore how personalised nutritional information impacts glycaemic control and patient-reported outcome measures (PROMs) of well-being. Free-living people with T2D eating their normal diet were provided with personalised nutritional recommendations by state-registered nutritionists based on the CGM-enabled analysis of individual post-prandial glycaemic responses (PPGRs). Participants demonstrated considerable inter-individual differences in PPGRs, reductions in post-prandial incremental area under the curve (iAUC) and daytime AUC, and improvements in energy levels, ability to concentrate, and other PROMs. These results suggest a role for personalised nutritional recommendations based on individual-level understanding of PPGRs in the non-pharmaceutical management of T2D. [ABSTRACT FROM AUTHOR]

When people face a health problem, they often first ask, 'Is there an app for that?'. We investigated the quality of advice provided by the Ada symptom assessment application to address the question, 'How do I know the app on my phone is safe and provides good advice?'. The app was tested with 48 independently created vignettes developed for a previous study, including 18 specifically developed for the Australian setting, using an independently developed methodology to evaluate the accuracy of condition suggestions and urgency advice. The correct condition was listed first in 65% of vignettes, and in the Top 3 results in 83% of vignettes. The urgency advice in the app exactly matched the gold standard 63% of vignettes. The app's accuracy of condition suggestion and urgency advice is higher than that of the best-performing symptom assessment app reported in a previous study (61%, 77% and 52% for conditions suggested in the Top 1, Top 3 and exactly matching urgency advice respectively). These results are relevant to the application of symptom assessment in primary and community health, where medical quality and safety should determine app choice. In 2021, when we face a health problem we often first ask, 'Is there an app for that?'. We investigated the quality of advice of the popular Ada symptom assessment app and compared it to the literature to answer the question, 'How do I know the app on my phone is safe and provides quality advice?' Ada's condition suggestion accuracy and its provision of appropriate urgency advice is higher than of other symptom assessment apps evaluated in this context in the literature. [ABSTRACT FROM AUTHOR]

Purpose: To review the results of the Moorfields Safer Surgery System (MSSS) for trabeculectomy, recently introduced in Malta. Methods: Patient files were reviewed from data collected over an 18 month period, from Mater Dei Hospital. Files of all patients undergoing primary trabeculectomy with a minimum of 12 months follow up data available were reviewed. Primary outcome measure of success was defined as a 30% drop in final post-operative intraocular pressure (IOP) at 1 year. The secondary outcome measure of success was a final post-op IOP of less than 21mmHg. Unqualified success was defined as a satisfactory IOP without the need of anti-glaucoma medication, while qualified success was defined as a satisfactory IOP in those patients requiring antiglaucoma medication. Results: 43 eyes (mean age = 66.2 yrs ± 11.7) were analysed. The mean pre-operative IOP was 27.0mmHg ± 4.6. The mean post-op IOP at one year was 15.3mmHg ±2.7. Unqualified success for the primary outcome measure was achieved in 64.1% of patients while the qualified success was achieved in 82.1%. Unqualified success for the secondary outcome measure was achieved in 72.7%, while a qualified success of 94.8% was obtained. There was a 6.8% failure rate. Conclusions: The results from this first review using the Moorfields safe surgery system for Trabeculectomy surgery in the Maltese islands compares well to the current literature. [ABSTRACT FROM AUTHOR]

Background: Silicone oils of different viscosities are used in the treatment of retinal detachments of varying pathology. Method: Seventy-two cases of retinal detachments managed with silicone oil were reviewed in a retrospective chart analyses. Eighty nine patients were reviewed from which data on primary pathology, type of silicone oil, duration of oil "in situ" and complications (including emulsification, increased intraocular pressure (IOP), re-detachment, cataract and presence of CME) were compiled. Of this number, 72 patients with postoperative follow-up of two years or more and documentation of the above parameters were included. The data was carefully analysed in an effort to determine the primary factor or factors of the varying silicone oil substitutes utilized responsible for the successful or non-successful reattachment of the retina. Results: Retinal re-detachment rate is greater when Silicone Oil (SO) is removed before 12 months. Complex vs non-complex retinal redetachments in sub-group analysis indicates superiority of retention of SO for greater than 12 months. Emulsification is greater in low viscosity SO (1300cts). Conclusion: The complication rates witnessed in this retrospective study are comparable to the findings of published studies present in the ophthalmic literature on an international scale. The findings of this study support the hypothesis that it is the duration of the SO "in situ" as opposed to the viscosity or other SO attributes which ultimately influences the re-detachment rate. [ABSTRACT FROM AUTHOR]

A fifty-eight year old male patient presented to the ophthalmic department with a 3 day history of reduced visual acuity, blurred vision and floaters, associated with recent lethargy, headaches and behavioural changes. Fundal examination revealed a bilateral vitritis. Steroid therapy was started. MRI of the brain revealed multiple hypodense and hyperdense lesions. Vitrectomy was performed in view of the poor response to steroids. A biopsy showed non-hodgkin B-Cell lymphoma. The patient was started on intravenous Methotrexate and Cytarabine. Repeat vitreous cavity biopsies were performed in order to assess response to therapy. All biopsies to date have revealed evidence of on-going lymphoma. [ABSTRACT FROM AUTHOR]

A twenty-two year old female patient presented with new onset bilateral hard orbital masses and progressively worse tear lake problems. Computed tomography of the orbits revealed poorly differentiated bilateral orbital masses. Laboratory investigation revealed ANCA positivity. Routine biochemical investigations were all within normal limits. CXR was also normal. Biopsy of the orbital masses revealed non-specific histological findings. An initial diagnosis of Granulomatosis with Polyangitis (GPA) was postulated. Oral steroids were given followed by a rapid response to steroid therapy. The working diagnosis of GPA was abandoned and a diagnosis of idiopathic orbital inflammation (IOI), or orbital pseudotumour was made owing to the benign, non-infective, inflammatory pathology with no evident systemic or local cause. Tailoring off of steroids resulted in repeated flare ups, resulting in the initiation of methotrexate therapy. The patient is in remission and is currently on combined steroid and methotrexate treatment. IOI is a diagnosis of exclusion and a rapid response to steroids serves as a diagnostic aid but is not in itself diagnostic. [ABSTRACT FROM AUTHOR]

A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS). We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by "immunogene" nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12) as DNA carrier was conjugated to an antibody (MLR2) to the neurotrophin receptor p75 (p75NTR). We used a plasmid (pVIVO2) designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP). MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice, GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0% of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo. [ABSTRACT FROM AUTHOR]

Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

One of the greatest strengths of artificial intelligence (AI) and machine learning (ML) approaches in health care is that their performance can be continually improved based on updates from automated learning from data. However, health care ML models are currently essentially regulated under provisions that were developed for an earlier age of slowly updated medical devices-requiring major documentation reshape and revalidation with every major update of the model generated by the ML algorithm. This creates minor problems for models that will be retrained and updated only occasionally, but major problems for models that will learn from data in real time or near real time. Regulators have announced action plans for fundamental changes in regulatory approaches. In this Viewpoint, we examine the current regulatory frameworks and developments in this domain. The status quo and recent developments are reviewed, and we argue that these innovative approaches to health care need matching innovative approaches to regulation and that these approaches will bring benefits for patients. International perspectives from the World Health Organization, and the Food and Drug Administration's proposed approach, based around oversight of tool developers' quality management systems and defined algorithm change protocols, offer a much-needed paradigm shift, and strive for a balanced approach to enabling rapid improvements in health care through AI innovation while simultaneously ensuring patient safety. The draft European Union (EU) regulatory framework indicates similar approaches, but no detail has yet been provided on how algorithm change protocols will be implemented in the EU. We argue that detail must be provided, and we describe how this could be done in a manner that would allow the full benefits of AI/ML-based innovation for EU patients and health care systems to be realized. [ABSTRACT FROM AUTHOR]

Related Articles Comment on: https://www.jmir.org/2020/12/e18097 Comment in: https://www.jmir.org/2021/6/e29336 J Med Internet Res 2021;23(6):e26514 doi:10.2196/26514 [ABSTRACT FROM AUTHOR]

This study aimed to describe a case series of patients diagnosed with orbital reactive lymphoid hyperplasia (RLH) at a single tertiary care centre. A retrospective review was conducted by searching electronic medical records at Liverpool University NHS Foundation Trust (LUHFT) from 1 st December 2021 - 1 st December 2023, to identify all patients with a histological diagnosis. Ten patients with an orbital histological diagnosis of RLH were identified. Median age at diagnosis was 56.5 years. Proptosis was the most prevalent presenting symptom, while other signs included palpable mass, ptosis, and diplopia. Eight patients were treated with oral prednisolone, with 20% (two) achieving complete remission. Additional treatments utilised in these cases encompassed doxycycline, mycophenolate, ciclosporin, and azathioprine.This case series represents one of the few reports focusing exclusively on orbital RLH. Notably, bone erosion was observed in this study, a finding that has been scarcely linked to RLH in the literature., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Reproductive health conditions such as endometriosis, uterine fibroids, and polycystic ovary syndrome (PCOS) affect a large proportion of women and people who menstruate worldwide. Prevalence estimates for these conditions range from 5% to 40% of women of reproductive age. Long diagnostic delays, up to 12 years, are common and contribute to health complications and increased health care costs. Symptom checker apps provide users with information and tools to better understand their symptoms and thus have the potential to reduce the time to diagnosis for reproductive health conditions., Objective: This study aimed to evaluate the agreement between clinicians and 3 symptom checkers (developed by Flo Health UK Limited) in assessing symptoms of endometriosis, uterine fibroids, and PCOS using vignettes. We also aimed to present a robust example of vignette case creation, review, and classification in the context of predeployment testing and validation of digital health symptom checker tools., Methods: Independent general practitioners were recruited to create clinical case vignettes of simulated users for the purpose of testing each condition symptom checker; vignettes created for each condition contained a mixture of condition-positive and condition-negative outcomes. A second panel of general practitioners then reviewed, approved, and modified (if necessary) each vignette. A third group of general practitioners reviewed each vignette case and designated a final classification. Vignettes were then entered into the symptom checkers by a fourth, different group of general practitioners. The outcomes of each symptom checker were then compared with the final classification of each vignette to produce accuracy metrics including percent agreement, sensitivity, specificity, positive predictive value, and negative predictive value., Results: A total of 24 cases were created per condition. Overall, exact matches between the vignette general practitioner classification and the symptom checker outcome were 83% (n=20) for endometriosis, 83% (n=20) for uterine fibroids, and 88% (n=21) for PCOS. For each symptom checker, sensitivity was reported as 81.8% for endometriosis, 84.6% for uterine fibroids, and 100% for PCOS; specificity was reported as 84.6% for endometriosis, 81.8% for uterine fibroids, and 75% for PCOS; positive predictive value was reported as 81.8% for endometriosis, 84.6% for uterine fibroids, 80% for PCOS; and negative predictive value was reported as 84.6% for endometriosis, 81.8% for uterine fibroids, and 100% for PCOS., Conclusions: The single-condition symptom checkers have high levels of agreement with general practitioner classification for endometriosis, uterine fibroids, and PCOS. Given long delays in diagnosis for many reproductive health conditions, which lead to increased medical costs and potential health complications for individuals and health care providers, innovative health apps and symptom checkers hold the potential to improve care pathways., (©Kimberly Peven, Aidan P Wickham, Octavia Wilks, Yusuf C Kaplan, Andrei Marhol, Saddif Ahmed, Ryan Bamford, Adam C Cunningham, Carley Prentice, András Meczner, Matthew Fenech, Stephen Gilbert, Anna Klepchukova, Sonia Ponzo, Liudmila Zhaunova. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 05.12.2023.)

Purpose: To compare the clinical outcomes of eye bank preloaded Descemet stripping automated endothelial keratoplasty (DSAEK) grafts and surgeon prepared., Methods: In this retrospective study, the data were obtained from two groups (a) surgeon cut DSAEK where tissue was prepared by the surgeon immediately before surgery, and (b) preloaded DSAEK tissue shipped to the surgeon after preparation by the eye bank. Standard DSAEK preparations using Moria microkeratome with single pass method were performed. For the tissues prepared by the eye banks, they were preloaded in an iGlide device and shipped in transport media. Standard DSAEK surgery using bimanual pull-through technique was performed for all the grafts. Air was used as a tamponade. Main outcome measures included best corrected visual acuity (BCVA) and rebubbling rate., Result: Out of 107 eyes of 101 patients that underwent DSAEK surgery, 33 tissues were prepared by the surgeon (sc-DSAEK), while 74 were prepared by the eye bank (pl-DSAEK). sc-DSAEK showed a rebubbling rate of 9.1%, compared to the 16.2% for the preloaded DSAEK ( p  = 0.11). There was no statistical difference in postoperative BCVA between the two groups. Logistic regression analysis showed no association between detachment rate and cataract surgery, graft preparation method, graft diameter and reason for graft., Conclusion: Preloaded grafts have similar rebubbling rate and visual acuity achieved compared with surgeon prepared grafts.

Objective: To compare clinical outcomes and complications between pre-loaded ultra-thin Descemet stripping automated endothelialkeratoplasty (pl-UT-DSAEK) and pre-loaded Descemet membrane endothelial keratoplasty (pl-DMEK)., Methods and Analysis: Comparative study in patients with endothelial dysfunction associated with Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy who underwent pl-UT-DSAEK or pl-DMEK transplants. For both groups, the tissues were pre-loaded at the Fondazione Banca degli Occhi del Veneto (Venice, Italy) and shipped to The Royal Liverpool University Hospital (Liverpool, UK). Best corrected visual acuity (BCVA) and re-bubbling rates were the main outcome measures., Results: 56 eyes of 56 patients were included. 31 received pl-UT-DSAEK and 25 received pl-DMEK. At 12 months, BCVA (LogMAR) was significantly better for pl-DMEK (0.17±0.20 LogMAR) compared with pl-UT-DSAEK (0.37±0.37 LogMAR, p<0.01). The percentage of people that achieved ≥20/30 was significantly higher in the pl-DMEK group. The rate of re-bubbling, however, was significantly higher for pl-DMEK (44.0%) than for Pl-UT-DSAEK (12.9%), p<0.01., Conclusion: Pl-DMEK offers better BCVA than pl-UT-DSAEK. The higher re-bubbling rate associated with pre-loaded DMEK is of concern., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Imaging and cardiology are the healthcare domains which have seen the greatest number of FDA approvals for novel data-driven technologies, such as artificial intelligence, in recent years. The increasing use of such data-driven technologies in healthcare is presenting a series of important challenges to healthcare practitioners, policymakers, and patients. In this paper, we review ten ethical, social, and political challenges raised by these technologies. These range from relatively pragmatic concerns about data acquisition to potentially more abstract issues around how these technologies will impact the relationships between practitioners and their patients, and between healthcare providers themselves. We describe what is being done in the United Kingdom to identify the principles that should guide AI development for health applications, as well as more recent efforts to convert adherence to these principles into more practical policy. We also consider the approaches being taken by healthcare organizations and regulators in the European Union, the United States, and other countries. Finally, we discuss ways by which researchers and frontline clinicians, in cardiac imaging and more broadly, can ensure that these technologies are acceptable to their patients., (Copyright © 2020 Fenech and Buston.)

This study addressed the suitability of the NSC-34 cell line as a motor neuron-like model for investigating neurotrophin receptor trafficking and associated subcellular processes. Initially, culture conditions were optimized for the use of NSC-34 cells in confocal microscopy. Cell surface markers, as well as markers associated with the regulated endosomal pathway thought to be associated with neurotrophin receptor transport, were identified. The study revealed the presence of a number of molecules previously not described in the literature, including the tropomyosin-like receptor kinase C (TrkC), sortilin, the vesicular acetylcholine transporter (VAChT), and the lipid raft-associated ganglioside GT1b. The presence of both sortilin and Gt1b was of special interest, insofar as these markers have been implicated in direct relationships with the p75NTR receptor. Evidence is provided for neurotrophin-dependent internalization of p75NTR and TrkB. Both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) increased the rate of internalization of p75NTR, with internalization dynamics comparable to those described for other cell lines. Thus, these studies not only describe components of the regulatory process governing the trafficking of this important receptor but also clearly demonstrate the value of NSC-34 cells as a suitable motor neuron model for the study of internalization and trafficking of cell surface molecules., ((c) 2007 Wiley-Liss, Inc.)