Micro-Meta App: an interactive tool for collecting microscopy metadata based on community specifications.

For quality, interpretation, reproducibility and sharing value, microscopy images should be accompanied by detailed descriptions of the conditions that were used to produce them. Micro-Meta App is an intuitive, highly interoperable, open-source software tool that was developed in the context of the 4D Nucleome (4DN) consortium and is designed to facilitate the extraction and collection of relevant microscopy metadata as specified by the recent 4DN-BINA-OME tiered-system of Microscopy Metadata specifications. In addition to substantially lowering the burden of quality assurance, the visual nature of Micro-Meta App makes it particularly suited for training purposes.

Promoting padawans: a survey examining the state of mentorship in neurosurgical training in the United Kingdom.

BACKGROUND: Mentorship has long since been acknowledged as an integral part of Neurosurgical training. The authors sought to evaluate the state of mentorship in Neurosurgical training in the United Kingdom (UK). METHODS: A 28-point questionnaire was sent to all neurosurgical trainees in the UK and Ireland via the British Neurosurgical Trainee's Association (BNTA), comprising 180 trainees. RESULTS: There were 75 responses (180 trainees on the mailing list, 42% response rate). Despite all respondents reporting it to be at least somewhat important to have a mentor, 16% felt they had no mentors. The mean number of mentors was 2.91 with 72% of respondents having more than 1 mentor. In terms of the content of mentorship relationships, 63% were comfortable discussing career related topics with their mentor to a high or very high degree but only 29% felt comfortable discussing their general wellbeing. With regards to allocated educational supervisors, 43% thought this person to be a 'low' or 'very low' source of mentorship. The three most important traits of the ideal mentor as reported by respondents were: someone chosen by them (48%), working in the same hospital (44%) and having received formal mentorship training (36%). CONCLUSIONS: The current perception of mentorship in Neurosurgery from the surveyed trainees is mixed. A healthy majority of trainees benefit from mentorship of some kind, whilst a significant minority feel underserved. The surveyed trainees feel mentorship is slanted more towards clinical and professional aspects of development than it is towards personal ones. Suggestions for future insight would be an evaluation of senior registrar and consultant sentiments towards mentorship, whilst exploration into more flexible models for establishing mentoring relationships may help to address the heavy importance of trainee choice which is voiced by this survey's results.

Burnout amongst neurosurgical trainees in the UK and Ireland.

INTRODUCTION: Burnout is becoming an increasingly recognised phenomenon within the medical profession. This study aims to investigate the presence of burnout amongst neurosurgical trainees in the UK and Ireland as well as investigating potential exacerbating and protective factors. METHOD: An online survey was sent to all neurosurgical trainees in the UK and Ireland via the British Neurosurgical Trainees' Association (BNTA) mailing list. Responding participants anonymously completed the Copenhagen Burnout Inventory (CBI) and answered questions about known risk factors for burnout including workplace environment, workplace bullying, time spent on leisure activities and sleep and reported likelihood of leaving neurosurgery. We also collated data on responders' demographics. We compared CBI scores for participants with and without risk factors to determine correlation with CBI. RESULTS: There were 75 respondents (response rate 42%) from a range of ages and all training grades, 72% of whom were male. The median CBI score was 38.85 (IQR 17.76). Participants showed a higher degree of personal and workplace burnout (median CBIs of 47.02, IQR 25.00; and 49.14, IQR 19.64, respectively) compared with patient-related burnout (median CBI 18.67, IQR 25.00). Participants with the following self-reported risk factors were significantly more likely to have higher CBIs: workplace bullying (p = 0.01), getting on less well with colleagues (p < 0.05), working longer hours (p < 0.05) and insufficient sleep, exercise and leisure time (all p < 0.01). Those with higher CBI scores were more likely to consider leaving neurosurgical training (p = 0.01). CONCLUSION: We identified a high burnout incidence in a cohort representative of UK neurosurgical trainees, although our results may have been skewed somewhat by selection bias. We determined potential risk factors for burnout related to specific workplace stressors and time for non-work activities. In the future, changes to training curricula should address these issues, aiming to improve training, enhance patient care and reduce attrition rates.

Acute bilateral foot drop with or without cauda equina syndrome-a case series.

INTRODUCTION: Isolated acute bilateral foot drop due to degenerative spine disease is an extremely rare neurosurgical presentation, whilst the literature is rich with accounts of chronic bilateral foot drop occurring as a sequela of systemic illnesses. We present, to our knowledge, the largest case series of acute bilateral foot drop, with trauma and relevant systemic illness excluded. METHODS: Data from three different centres had been collected at the time of historic treatment, and records were subsequently reviewed retrospectively, documenting the clinical presentation, radiological level of compression, timing of surgery, and degree of neurological recovery. RESULTS: Seven patients are presented. The mean age at presentation was 52.1 years (range 41-66). All patients but one were male. All had a painful radiculopathic presentation. Relevant discopathy was observed from L2/3 to L5/S1, the commonest level being L3/4. Five were treated within 24 h of presentation, and two within 48 h. Three had concomitant cauda equina syndrome; of these, the first two made a full motor recovery, one by 6 weeks follow-up and the second on the same-day post-op evaluation. Overall, five out of seven cases had full resolution of their ankle dorsiflexion pareses. One patient with 1/5 power has not improved. Another with 1/5 weakness improved to normal on the one side and to 3/5 on the other. CONCLUSION: When bilateral foot drop occurs acutely, we encourage the consideration of degenerative spinal disease. Relevant discopathy was observed from L2/3 to L5/S1; aberrant innervation may be at play. Cauda equina syndrome is not necessarily associated with acute bilateral foot drop. The prognosis seems to be pretty good with respect to recovery of the foot drop, especially if partial at presentation and if treated within 48 h.

Genetic manipulation allows in vivo tracking of the life cycle of the son-killer symbiont, Arsenophonus nasoniae, and reveals patterns of host invasion, tropism and pathology.

Maternally heritable symbionts are common in arthropods and represent important partners and antagonists. A major impediment to understanding the mechanistic basis of these symbioses has been lack of genetic manipulation tools, for instance, those enabling transgenic GFP expression systems for in vivo visualization. Here, we transform the 'son-killer' reproductive parasite Arsenophonus nasoniae that infects the parasitic wasp Nasonia vitripennis with the plasmid pOM1-gfp, re-introduce this strain to N. vitripennis and then used this system to track symbiont life history in vivo. These data revealed transfer of the symbiont into the fly pupa by N. vitripennis during oviposition and N. vitripennis larvae developing infection over time through feeding. A strong tropism of A. nasoniae to the N. vitripennis ovipositor developed during wasp pupation, which aids onward transmission. The symbiont was also visualized in diapause larvae. Occasional necrotic diapause larvae were observed which displayed intense systemic infection alongside widespread melanotic nodules indicative of an active but failed immune response. Our results provide the foundation for the study of this symbiosis through in vivo tracking of the fate of symbionts through host development, which is rarely achieved in heritable microbe/insect interactions.

Core-Shell Crystals of Porous Organic Cages.

The first examples of core-shell porous molecular crystals are described. The physical properties of the core-shell crystals, such as surface hydrophobicity, CO2 /CH4 selectivity, are controlled by the chemical composition of the shell. This shows that porous core-shell molecular crystals can exhibit synergistic properties that out-perform materials built from the individual, constituent molecules.

Controlling the network type in self-assembled dipeptide hydrogels.

We show that the same low molecular weight gelator can form gels using three different methods. Gels were formed from a high pH solution either by adding a salt or by adding an acid; gels were also formed by adding water to a solution of the gelator in an organic solvent. The mechanical properties for the gels formed by the different methods are different from one another. We link this to the network type that is formed, as well as the fibrous structures that are formed. The salt-triggered gels show a significant number of fibres that tend to align. The acid-triggered gels contain many thin fibres, which form an entangled network. The solvent-triggered gels show the presence of spherulitic domains. We show that it is tractable to vary the trigger mechanism for an established, robust gelator to prepare gels with targeted properties as opposed to synthesising new gelators.

Live Imaging of Cell Invasion Using a Multicellular Spheroid Model and Light-Sheet Microscopy.

Three-dimensional cellular assays are becoming increasingly popular as a fundamental tool to bridge the gap between tissue culture systems and in vivo tissue. In particular, spheroids are recognised today as a necessary intermediate model between testing in monolayer cultures and testing in animals. This chapter describes a straightforward protocol, from sample preparation to image acquisition and initial post-processing, based on one of most widely used commercial light-sheet fluorescence microscopy platform, the Zeiss Lightsheet Z.1.

A case of conservatively managed idiopathic spinal cord herniation presenting with low-pressure headache.

Idiopathic spinal cord herniation presenting with low-pressure headache is extremely rare. We present a case of thoracic ventral spinal cord herniation in a 35-year-old lady who presented with low-pressure headaches. To our knowledge, this is only the fourth case described in the literature of spontaneous ventral cord herniation presenting in this way. The patient was managed conservatively with no manifestation of focal neurological symptoms at 12-month follow-up. The proposed aetiology of spontaneous ventral cord herniation is an initial CSF leak via a dural defect, through which the cord subsequently also enters blocking the CSF leak. We endorse a conservative approach for patients who present similarly, secondary to the above pathophysiology.

Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion.

CCK is secreted by endocrine cells of the proximal intestine in response to dietary components, including amino acids. CCK plays a variety of roles in digestive processes, including inhibition of food intake, consistent with a role in satiety. In the lingual epithelium, the sensing of a broad spectrum of L-amino acids is accomplished by the heteromeric amino acid (umami) taste receptor (T1R1-T1R3). T1R1 and T1R3 subunits are also expressed in the intestine. A defining characteristic of umami sensing by T1R1-T1R3 is its potentiation by IMP or GMP. Furthermore, T1R1-T1R3 is not activated by Trp. We show here that, in response to L-amino acids (Phe, Leu, Glu, and Trp), but not D-amino acids, STC-1 enteroendocrine cells and mouse proximal small intestinal tissue explants secrete CCK and that IMP enhances Phe-, Leu-, and Glu-induced, but not Trp-induced, CCK secretion. Furthermore, small interfering RNA inhibition of T1R1 expression in STC-1 cells results in significant diminution of Phe-, Leu-, and Glu-stimulated, but not Trp-stimulated, CCK release. In STC-1 cells and mouse intestine, gurmarin inhibits Phe-, Leu-, and Glu-induced, but not Trp-stimulated, CCK secretion. In contrast, the Ca(2+)-sensing receptor antagonist NPS2143 inhibits Phe-stimulated CCK release partially and Trp-induced CCK secretion totally in mouse intestine. However, NPS2143 has no effect on Leu- or Glu-induced CCK secretion. Collectively, our data demonstrate that functional characteristics and cellular location of the gut-expressed T1R1-T1R3 support its role as a luminal sensor for Phe-, Leu-, and Glu-induced CCK secretion.

What is the quality of the information available on the internet for patients suffering with sciatica?

BACKGROUND: Sciatica is a common neurological condition with a wide variety of clinical specialists and allied health professionals involved, and a broad range of treatment options. We sought to assess the quality of information available on the internet. METHODS: An internet search for 'sciatica' was performed using 'Google'. The first fifty links were assessed using the DISCERN instrument, a validated questionnaire for health consumers and providers. RESULTS: After exclusions, 44 websites were assessed. Only 37% of sites had clear aims and objectives; 79% provided relevant information; 81% did not provide clear sources of their information; 67% had no indication of when the information was compiled or updated; 63% clarified that more than one treatment option was available; only 28% described in moderate to extensive detail how the various treatment modalities might work; only 14% informed patients of potential risks and complications for each treatment. The biased and/or unbalanced websites amounted to 40%, offering greater detail about one treatment modality over others. Overall, 93% of assessed websites did not inform patients of the consequences/natural history if no treatment were undertaken; and 91% did not describe the potential impact of treatment and how it could affect quality of life. CONCLUSIONS: Despite the role that the internet plays in everyday life, information on the common and debilitating condition of sciatica is mostly of low-to-moderate quality, and with serious shortcomings. Healthcare stakeholders ought to be aware of the risks of misinformation and ensure that health-related internet website design and upkeep is guided by instruments such as DISCERN.

Comparison of External Ventricular Drains with Ventricular Access Devices for the Emergency Management of Adult Hydrocephalus.

OBJECTIVE: We compared external ventricular drains (EVDs) with percutaneous continuous cerebrospinal fluid (CSF) drainage via ventricular access devices (VADs) for the acute management of hydrocephalus in adults. METHODS: This was a retrospective review of all ventricular drains inserted for a new diagnosis of hydrocephalus into noninfected CSF over four years. We compared infection rates, return to theatre, and patient outcome between EVDs and VADs. We explored the effect of duration of drainage, frequency of sampling, hydrocephalus aetiology, and catheter location on these outcomes using multivariable logistic regression modelling. RESULTS: We included 179 drains (76 EVDs and 103 VADs). EVDs were associated with a higher rate of unplanned return to theatre for replacement or revision (27/76, 36%, vs. 4/103, 4%, OR: 13.4 95%CI: 4.3-55.8). However, infection rates were higher in VADs (13/103, 13% vs. 5/76, 7%, OR: 2.0, 95%CI: 0.65-7.7). EVDs were 91% antibiotic impregnated whereas VADs were 98% nonimpregnated. In multivariable analysis, infection was associated with duration of drainage (median: 11 days prior to infection for infected drains vs. 7 days total for noninfected drains), but not drain type (VADs vs. EVDs OR: 1.6, 95%CI: 0.5-6). CONCLUSIONS: EVDs had a higher rate of unplanned revisions but a lower infection rate compared to VADs. However, in multivariable analysis choice of drain type was not associated with infection. We suggest a prospective comparison of antibiotic impregnated VADs and EVDs using similar sampling protocols to assess whether VADs or EVDs for acute hydrocephalus have a lower overall complication rate.

Intra-arterial lidocaine therapy via the middle meningeal artery for migraine headache: Theory, current practice and future directions.

Recent developments in neurointerventional research have seen the emergence of the middle meningeal artery (MMA) as an effective conduit for intra-arterial (IA) therapy for a number of pathologies. Here, we review the anatomical, pathophysiological and experimental basis for utilisation of the MMA for IA treatment of migraine headache. We explore the in-human case literature for the treatment of headaches with IA lidocaine and discuss considerations and challenges for future research.

Management of traumatic atlanto-occipital dislocation in a 10-year-old with noninvasive halo immobilization: A case report.

Background: Traumatic atlanto-occipital dislocation is an unstable injury of the craniocervical junction. For pediatric patients, surgical arthrodesis of the occipitocervical junction is the recommended management. While having a high success rate for stabilization, the fusion comes with obvious morbidity of limitation in cervical spine flexion, extension, and rotation. An alternative is external immobilization with a conventional halo. Case Description: We describe the case of a 10-year-old boy who was treated successfully for traumatic AOD with a noninvasive pinless halo. Following initial brain trauma management, we immobilized the craniocervical junction with a pinless halo after reducing the atlanto-occipital dislocation. The pinless halo was kept on at all times for the next 3 months. The craniocervical junction alignment was monitored with weekly cervical spine X-rays and CT craniocervical junction on day 15th, day 30th, and day 70th. A follow-up MRI C-spine 3 months from presentation confirmed resolution of the soft-tissue injury and the pinless halo was removed. Dynamic cervical spine X-rays revealed satisfactory alignment in both flexion and extension views. The patient has been followed up for 2 years postinjury and no issues were identified. Conclusion: Noninvasive pinless halo is a potential treatment option for traumatic pediatric atlanto-occipital dislocation. This should be considered bearing in mind multiple factors including age and weight of the patient, severity of the atlanto-occipital dislocation (Grade I vs. Grade II and incomplete vs. complete), concomitant skull and scalp injury, and patient's ability to tolerate the halo. It is vital to emphasize that this necessitates close clinicoradiological monitoring.

Adult WHO grade II ependymomas: is Ki67 a sex-specific proliferation marker?

Ki67 is a marker for proliferation of a given cell population. Low expression of Ki67 may be associated with a favourable outcome. We investigate how the proliferation index correlates with the location, morphology and behaviour of WHO grade II ependymomas with a single-centre cohort study of adult patients admitted for surgery of WHO grade II ependymomas between 2008 and 2018. Seventeen patients were included, seven had supratentorial and 10 had infratentorial tumours. Three patients died and eight had recurrent disease. Age, gender, location, extent of resection, chemotherapy, radiotherapy and histological markers were not associated with tumour progression. Both unadjusted and adjusted analysis confirmed a higher Ki67 index in male patients. Sensitivity analysis further supported the correlation between Ki67 and male gender. Ki67 may be sex specific but does not seem to correlate with survival and time to recurrence in this series.

Madin-Darby canine kidney cells are increased in aerobic glycolysis when cultured on flat and stiff collagen-coated surfaces rather than in physiological 3-D cultures.

We investigate the influence of the dimensionality and the biochemistry of the culture system on the cellular functionality by analyzing the protein expression levels in Madin-Darby canine kidney (MDCK) cells grown in 3-D and 2-D substrates. We cultured MDCK cells on a hard and flat 2-D uncoated plastic surface, on a 2-D collagen-coated plastic surface and in 3-D collagen gel and employed 2-D gel electrophoresis, MALDI-TOF-MS, and LC-MS/MS analysis to identify the differentially regulated proteins. We found significant differences in the expression of antioxidant proteins, actin-binding proteins, glycolytic enzymes, and heat-shock proteins/chaperons among the three types of cultures. While MDCK cells cultured in 3-D collagen up-regulate antioxidant proteins and proteins involved in the dynamic remodeling of the actin cytoskeleton, 2-D collagen-coated plastic surfaces induce the up-regulation of glycolytic enzymes. Our data shows that the culture conditions have profound effects on the physiology of the cell. Culture in 3-D collagen induces a differentiated polarized phenotype. In contrast, collagen-coated 2-D substrates favor a tumor-like phenotype with increased glycolysis. Thus, the suitability of 2-D cultures to study the physiological behavior of cells, especially in drug discovery, bioprocessing, and toxicology, should be carefully reconsidered.

Spatial and temporal information coding and noise in the NF-κB system.

NF-κB (nuclear factor κB) regulates cellular stress and the immune responses to infection. Its activation results in oscillations in nuclear NF-κB abundance. We treated cells with repeated short pulses of TNFα (tumour necrosis factor α) at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals analysed, we observed synchronous cycles of NF-κB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave translocations with reduced amplitude, indicating that the system failed to reset completely. Deterministic and stochastic mathematical models predicted how negative feedback loops might regulate both system resetting and cellular heterogeneity. Altering the stimulation interval gave different patterns of NF-κB-dependent gene expression, supporting a functional role for oscillation frequency. The causes of cell-to-cell variation and the possible functions of these processes in cells and tissues are discussed. The NF-κB system is just one of a number of known biological oscillators that include calcium signalling, transcription cycles, p53, the segmentation clock, the circadian clock, the cell cycle and seasonal rhythms. The way such cycles are integrated could be part of the answer as to how organisms achieve complexity while retaining the robustness of cellular decision-making processes.

Interactive segmentation of clustered cells via geodesic commute distance and constrained density weighted Nyström method.

An interactive method is proposed for complex cell segmentation, in particular of clustered cells. This article has two main contributions: First, we explore a hybrid combination of the random walk and the geodesic graph based methods for image segmentation and propose the novel concept of geodesic commute distance to classify pixels. The computation of geodesic commute distance requires an eigenvector decomposition of the weighted Laplacian matrix of a graph constructed from the image to be segmented. Second, by incorporating pairwise constraints from seeds into the algorithm, we present a novel method for eigenvector decomposition, namely a constrained density weighted Nyström method. Both visual and quantitative comparison with other semiautomatic algorithms including Voronoi-based segmentation, grow cut, graph cuts, random walk, and geodesic method are given to evaluate the performance of the proposed method, which is a powerful tool for quantitative analysis of clustered cell images in live cell imaging.

Trypanosoma brucei colonizes the tsetse gut via an immature peritrophic matrix in the proventriculus.

The peritrophic matrix of blood-feeding insects is a chitinous structure that forms a protective barrier against oral pathogens and abrasive particles1. Tsetse flies transmit Trypanosoma brucei, which is the parasite that causes human sleeping sickness and is also partially responsible for animal trypanosomiasis in Sub-Saharan Africa. For this parasite to establish an infection in flies, it must first colonize the area between the peritrophic matrix and gut epithelium called the ectoperitrophic space. Although unproven, it is generally accepted that trypanosomes reach the ectoperitrophic space by penetrating the peritrophic matrix in the anterior midgut2-4. Here, we revisited this event using fluorescence- and electron-microscopy methodologies. We show that trypanosomes penetrate the ectoperitrophic space in which the newly made peritrophic matrix is synthesized by the proventriculus. Our model describes how these proventriculus-colonizing parasites can either migrate to the ectoperitrophic space or become trapped within peritrophic matrix layers to form cyst-like bodies that are passively pushed along the gut as the matrix gets remodelled. Furthermore, early proventricular colonization seems to be promoted by factors in trypanosome-infected blood that cause higher salivary gland infections and potentially increase parasite transmission.