Electrostatically Cross-Linked Bioinks for Jetting-Based Bioprinting of 3D Cell Cultures.

It has been acknowledged that thousands of drugs that passed two-dimensional (2D) cell culture models and animal studies often fail when entering human clinical trials. Despite the significant development of three-dimensional (3D) models, developing a high-throughput model that can be reproducible on a scale remains challenging. One of the main challenges is precise cell deposition and the formation of a controllable number of spheroids to achieve more reproducible results for drug discovery and treatment applications. Furthermore, when transitioning from manually generated structures to 3D bioprinted structures, the choice of material is limited due to restrictions on materials that are applicable with bioprinters. Herein, we have shown the capability of a fast-cross-linking bioink that can be used to create a single spheroid with varying diameters (660, 1100, and 1340 µm) in a high-throughput manner using a commercialized drop-on-demand bioprinter. Throughout this work, we evaluate the physical properties of printable ink with and without cells, printing optimization, cytocompatibility, cell sedimentation, and homogeneity in ink during the printing process. This work showcases the importance of ink characterization to determine printability and precise cell deposition. The knowledge gained from this work will accelerate the development of next-generation inks compatible with a drop-on-demand 3D bioprinter for various applications such as precision models to mimic diseases, toxicity tests, and the drug development process.

Cascade screening for glaucoma in high-risk family members of African-Caribbean glaucoma patients in an urban population in London.

BACKGROUND/AIMS: Cascade screening has been used successfully in relatives of patients with inherited cancers and other genetic diseases to identify presymptomatic disease. This study was designed to examine if this approach would be successful in a high-risk group: first-degree relatives (FDR) of African-Caribbean glaucoma patients resident in London. METHODS: African-Caribbean patients (probands) with glaucoma from an inner London hospital setting in a deprived area were asked to disseminate personalised information to their FDR over the age of 30 and to arrange a free hospital-based screening. Data collected, including optical coherence tomography imaging, were reviewed by a glaucoma specialist and if glaucoma was diagnosed or suspected, local specialist referral via family doctor was made. RESULTS: 203 probands were recruited from glaucoma clinics. 248 suitable FDR were identified as potentially eligible to attend screening. 57 (23%) FDR made contact with the research team of whom 18 (7%) attended a subsequent screening visit. No patients were diagnosed with glaucoma; one participant was diagnosed as glaucoma suspect. Reasons for poor uptake included reluctance by probands to involve their family members, and retirees spending significant time abroad. CONCLUSION: Cascade screening of FDR of African-Caribbean glaucoma patients in inner city London was unsuccessful. Research confidentiality guidance prohibiting research teams directly contacting family members was a barrier. Greater community engagement, community-based screening and permission to contact FDR directly might have improved uptake.

Feasibility and acceptability of a home-based resistance training intervention in adolescent and young adult hematopoietic cell transplant survivors.

BACKGROUND: Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness, and reduce risk of cardiovascular disease. PROCEDURE: Eligible participants ages 13-39 years, 80-120 days post-HCT, transfusion independent, and prednisone dose ≤1 mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics, and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were (a) 60% enrollment of approached patients, (b) 80% completion of weekly phone calls, and (c) 80% completion of the RT intervention and FU1 assessments. Acceptability was based on positive responses in qualitative interviews. RESULTS: Twenty of 31 (65%) eligible AYAs enrolled. Three participants failed to complete baseline measurements (2 = scheduling barriers, 1 = passive refusal) and four participants who completed baseline assessments did not receive the intervention (1 = medical reasons, 2 = no longer interested). Of those who completed baseline assessments, 13 received the intervention, completed 88.5% of coaching calls, and 11 (65%) completed FU1. LBM (kg) increased or remained unchanged in nine of nine participants with complete body composition data at FU1 (mean 1.1 kg; 95%CI: 0.4, 1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. CONCLUSIONS: A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.

Anisocoria in an intubated patient with COVID-19.

The effects of COVID-19 on the eye are still widely unknown. We describe a case of a patient who was intubated and proned in the intensive care unit (ICU) for COVID-19 and developed unilateral anisocoria. CT venogram excluded a cavernous sinus thrombosis. MRI of the head showed microhaemorrhages in the midbrain where the pupil reflex nuclei are located. After the patient was stepped down from ICU, intraocular pressure (IOP) was found to be raised in that eye. A diagnosis of subacute closed angle glaucoma was made. It is important for clinicians to rule out thrombotic causes in patients who develop acute anisocoria. It is also crucial to measure IOP in patients who develop ophthalmic pathology and have been proned for extended periods.

Pituitary apoplexy and associated cranial nerve palsies secondary to bleeding caused by immune thrombocytopaenia in a patient with known pituitary macroadenoma.

An 84-year-old man presented with a frontal headache and easy bruising. He had a background history of a pituitary macroadenoma, diagnosed incidentally a year earlier. Investigations showed haemorrhage into the pituitary macroadenoma leading to a diagnosis of pituitary apoplexy in the context of low platelet count secondary to immune thrombocytopaenia. He was treated with intravenous hydrocortisone, platelet transfusion, intravenous immunoglobulin and high-dose steroid. Neurosurgical intervention was not indicated initially. Five days into his admission, he developed bilateral ptosis and ophthalmoplegia. MRI confirmed further haemorrhage associated with compression of the optic chiasm. He was transferred to a tertiary neurosurgical centre where he underwent urgent surgical decompression. To date, there has been minor improvement in his neurological symptoms. Management of this patient required considerable multidisciplinary teamwork between the clinics of endocrinology, haematology, neurosurgery, ophthalmology and geriatrics.

Human naive epiblast cells possess unrestricted lineage potential.

Classic embryological experiments have established that the early mouse embryo develops via sequential lineage bifurcations. The first segregated lineage is the trophectoderm, essential for blastocyst formation. Mouse naive epiblast and derivative embryonic stem cells are restricted accordingly from producing trophectoderm. Here we show, in contrast, that human naive embryonic stem cells readily make blastocyst trophectoderm and descendant trophoblast cell types. Trophectoderm was induced rapidly and efficiently by inhibition of ERK/mitogen-activated protein kinase (MAPK) and Nodal signaling. Transcriptome comparison with the human embryo substantiated direct formation of trophectoderm with subsequent differentiation into syncytiotrophoblast, cytotrophoblast, and downstream trophoblast stem cells. During pluripotency progression lineage potential switches from trophectoderm to amnion. Live-cell tracking revealed that epiblast cells in the human blastocyst are also able to produce trophectoderm. Thus, the paradigm of developmental specification coupled to lineage restriction does not apply to humans. Instead, epiblast plasticity and the potential for blastocyst regeneration are retained until implantation.

Recorded infection control messages delay inter-professional communication but are not associated with COVID-19 prevalence or mortality: insights from a national switchboard analysis.

Appropriate dissemination of information to the general public is a key component of the pandemic response. In 2018, recorded infection control advice messages were affixed to 30% of England's automated hospital switchboards during the seasonal influenza and norovirus outbreaks. As the majority of messages were mandatory for all callers, healthcare professionals using the hospital switchboard - including during time-critical emergencies - had their enquiries significantly delayed by these measures. Importantly, published analyses did not demonstrate an association between these messages and patient outcomes. As of May 2020, 85% of NHS trusts made use of infection control messages; on average, these delayed healthcare professionals by 59.4 seconds per call, but had no clear association with patient outcomes from COVID-19. An ongoing national switchboard quality improvement project seeks to establish a gold standard whereby healthcare professionals with urgent enquiries can press 'X' to skip past infection control messages and have their calls triaged immediately.

Comparing the clinical profile of adults and children with Behçet's syndrome in the UK.

OBJECTIVES: Behçet's syndrome (BS) is a rare multi-system inflammatory disorder. Clinical phenotypic variance across geographical regions is recognised but UK BS patients' variance by age groups and gender has not been studied. This study compares the clinical features of adult and juvenile onset Behçet's Syndrome (JBS) in a UK population. METHODS: Two clinical databases of BS patients were compared. The JBS database was collected at the Great Ormond Street Hospital for Children, London (n=46). The adult database was collected at the Hammersmith Hospital, London (n=560). RESULTS: Oro-genital aphthosis had high prevalence in both the JBS and the adult cohort (oral: 97.8% vs. 96.6%, genital: 73.9% vs. 75.7%). The JBS cohort was more likely to have gastrointestinal involvement (21.7% vs. 4.5%, p<0.001) and arthritis (21.7% vs. 9.6%, p=0.021) compared to adults. The JBS cohort was less likely to have eye involvement (4.3% vs. 37%, p<0.001), skin (21.7% vs. 55.4%, p<0.001) and vascular involvement (6.5% vs. 17.5% p=0.063). JBS females had a higher rate of genital aphthosis than JBS males (87.5% vs. 59.1%, p=0.044). Adult females had higher rates of genital (85.2% vs. 64.5%, p<0.001) and oral (99.0% vs. 93.8%, p=0.001) aphthosis than adult males. Adult males were more likely to have ophthalmological (44.9% vs. 30.3%, p<0.001) and vascular (23.0% vs. 12.8%, p=0.002) manifestations than adult females. CONCLUSIONS: UK JBS patients displayed less ocular and skin manifestations compared to the adult BS patients. This information will aid clinicians in diagnosing BS in UK adult and paediatric populations.

Orbital blowout fracture from nose blowing.

Orbital blowout fractures are nearly always caused by acute trauma. Non-traumatic cases of orbital blowout fractures have only been rarely described. In this case study, we discuss an orbital blowout fracture directly caused by nose blowing. The patient developed unilateral eye swelling and orbital emphysema. It is important for the clinician to investigate all suspected orbital blowout fractures with imaging and full ophthalmological examination regardless of a trauma history. Most cases of orbital emphysema resolve spontaneously, however one must always exclude compression of the central retinal artery. This may present as acute loss of vision and/or ophthalmoplegia.