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The COVID-19 pandemic requires mass screening to identify those infected for isolation and quarantine. Individually screening large populations for the novel pathogen, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is costly and requires a lot of resources. Sample pooling methods improve the efficiency of mass screening and consume less reagents by increasing the capacity of testing and reducing the number of experiments performed, and are therefore especially suitable for under-developed countries with limited resources. Here, we propose a simple, reliable pooling strategy for COVID-19 testing using clinical nasopharyngeal (NP) and/or oropharyngeal (OP) swabs. The strategy includes the pooling of 10 NP/OP swabs for extraction and subsequent testing via quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and may also be applied to the screening of other pathogens.

Objective  Early exposure to niche specialities, like neurosurgery, is essential to inform decisions about future training in these specialities. This study assesses the impact of a hands-on simulated aneurysm clipping workshop on medical students' and junior doctors' perceptions of neurosurgery at a student-organized neurosurgical conference. Methods  Ninety-six delegates were sampled from a hands-on workshop involving hydrogel three-dimensional printed aneurysms clipping using surgical microscopes. Consultant neurosurgeons facilitated the workshop. Changes in delegates' perceptions of neurosurgery were collected using Likert scale and free-text responses postconference. Results  Postworkshop, 82% of participants reported a positive impact on their perception of neurosurgery. Thematic analysis revealed that delegates valued the hands-on experience, exposure to microsurgery, and interactions with consultant neurosurgeons. Thirty-six of the 96 delegates (37.5%) expressed that the workshop dispelled preconceived fears surrounding neurosurgery and improved understanding of a neurosurgeon's day-to-day tasks. Several delegates initially apprehensive about neurosurgery were now considering it as a career. Conclusion  Hands-on simulated workshops can effectively influence medical students' and junior doctors' perceptions of neurosurgery, providing valuable exposure to the specialty. By providing a valuable and immersive introduction to the specialty, these workshops can help to dispel misconceptions, fears, and apprehensions associated with neurosurgery, allowing them to consider the specialty to a greater degree than before. This study of a one-time workshop cannot effectively establish its long-term impact on said perceptions, however., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Inner retinal atrophy has been demonstrated in schizophrenia spectrum disorder (SSD) using optical coherence tomography (OCT). This systematic review and meta-analysis investigated the role of contemporary Fourier domain OCT devices in SSD., Methods: MEDLINE, PubMed, Scopus, Embase, PsycInfo, PYSNDEX, World Health Organization, and Cochrane databases were searched from inception until May 2022. All peer-reviewed adult SSD case-control studies using Fourier domain OCT were included. Ocular pathologies known to affect retinal OCT scans were excluded. Search, data appraisal, and summary data extraction were independently performed by 2 authors., Results: The review criteria was met by k = 36 studies, with k = 24 studies (1074 cases, 854 controls) suitable for meta-analysis. The SSD group exhibited a thinner global peripapillary retinal nerve fiber layer (-3.26 μm, 95% CI, -5.07 to -1.45, I 2  = 64%, k = 21), thinner average macular layer (-7.88 μm, 95% CI, -12.73 to -3.04, I 2  = 65%, k = 11), and thinner macular ganglion cell-inner plexiform sublayer (-2.44 μm, 95% CI, -4.13 to -0.76, I 2  = 30%, k = 8) compared with the control group. Retinal nerve fiber layer findings remained significant after exclusion of metabolic disease, low quality, outlier, and influential studies. Studies involving eye examinations to exclude eye disease were associated with greater atrophy in SSD. Except for cardiometabolic disease, most studies did not report clinically significant covariate data known to influence retinal thickness., Conclusions: Individuals with SSD generally exhibited retinal atrophy, possibly paralleling reduced brain volumes documented in clinical imaging. Prospective longitudinal studies that collect clinical data, including various illness phases, and control for confounders will be necessary to evaluate retinal atrophy as a biomarker in SSD., (© 2023 The Authors.)

Background: Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported to occur after cataract surgery. It is not clearly established whether cataract surgery increases the risk of NAION over baseline., Evidence Acquisition: Medline, PubMed, Embase, and Cochrane Central registers were systematically searched for eligible studies reporting on postcataract surgery NAION (psNAION) within 1 year. All peer-reviewed publications with events n ≥ 10 were included. Pooled incidence and odds/hazard ratios and 95% confidence intervals (CIs) were extracted and calculated using random effect models for early and delayed psNAION. Time to event data were pooled for temporal analysis of psNAION events within the first year. This systematic review was registered (PROSPERO CRD42021274383)., Results: Nine articles met the selection criteria with five studies suitable for meta-analysis. A total of 320 psNAION cases, 1,307 spontaneous NAION (sNAION) cases, 1,587,691 cataract surgeries, and 1,538,897 noncataract surgery controls were included. Pooling of 63,823 cataract surgeries and 161,643 controls showed a hazard ratio of 4.6 (95% CI 2.7-7.8) of psNAION within 1 year of surgery. Pooled unadjusted incidence of psNAION within 2 months was 99.92 (95% CI 38.64-161.19) per 100,000/year, psNAION within 1 year was 32.36 (95% CI 9.38-55.34) per 100,000/year, and sNAION was 8.87 (95% CI 2.12-15.62) per 100,000/year. psNAION cases were older by a mean of 7.6 years; otherwise, pooled odds ratios for baseline risk factors in psNAION vs. sNAION cases were not statistically significant. psNAION within the first year peaked within 72 hrs and at 6 weeks after the surgery with 73% of cases occurring within 6 months., Conclusion: The risk of NAION after cataract surgery is four times greater within the first year and usually occurs within 6 months. However, the absolute risk remains low at 1 in 1,000-3,100 surgeries and is unlikely to warrant extra mention for consenting., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Purpose: To explore blinking patterns and sagittal eyelid misalignment in the East Asian eye., Methods: Forty-four participants (22 females; age 26 ± 5 years; 52% of East Asian ethnicity) were enrolled in this pilot study and subdivided, based on upper eyelid crease presence and extent, into single (n = 10), partial (n = 11) or double (n = 23) eyelid crease groups. Blinking was filmed surreptitiously with high-speed video simultaneously from an inferior temporal and frontal view. Spontaneous blink rate and type (incomplete, almost complete, or complete) were assessed over a 30 s period. Sagittal misalignment of the lids on closure was graded during complete spontaneous blinks, voluntary lid closure and voluntary maximal lid contraction (squeezing). A 0.15 µL drop of lissamine green was placed on the central lower lid margin and the number and type of blinks required to eliminate the drop informed complete palpebral apposition during blinking., Results: Mean ± SD blink rates averaged 16.9 ± 10.5 blinks/minute. The proportion of incomplete blinks was 83 ± 22% in single, 58 ± 35% in partial and 59 ± 30% in double eyelid crease groups. The sagittal misalignment of the lid margins during blinking was limited to approximately one-third of the lid margin width; this was similar for all lid morphologies and blink types. The lissamine green drop was eliminated only by voluntary maximal lid contraction, and was similar in all groups (p = 0.97)., Conclusions: Incomplete blinking and sagittal lid misalignment of the central eyelid margin predominate in habitual blinking, irrespective of lid morphology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Aims: To examine the role of early vitrectomy in the management of endophthalmitis from all causes., Methods: Retrospective study of 290 consecutive subjects diagnosed with endophthalmitis at Auckland District Health Board between 1 January 2006 and 31 July 2019. Main outcome measure was visual acuity at 9-month follow-up and proportion of subjects with severe vision loss (≤20/200)., Results: Median age at presentation was 70.4 years and 151 subjects (52.1%) were women. Cataract surgery was the most common cause of endophthalmitis in 92 subjects (31.7%) followed by intravitreal injection in 57 (19.7%), endogenous endophthalmitis in 48 subjects (16.6%), non-surgical trauma in 42 subjects (14.5%), glaucoma surgery in 24 subjects (8.3%), vitrectomy in 22 subjects (7.6%) and corneal in 5 subjects (1.7%). Culture was positive in 136 (46.9%) with gram-positive organisms most common (76.5%). Early vitrectomy was performed in 82 subjects (28.3%). Median visual acuity at 9 months was 20/100 (IQR 20/30 to light perception), and severe vision loss occurred in 100 (43.5%). Retinal detachment occurred in 35 eyes (12.1%) and 26 eyes were enucleated. On multivariate analysis, younger age, poor presenting visual acuity and culture-positive endophthalmitis were associated with worse outcomes, and early vitrectomy was associated with better outcomes., Conclusions: Early vitrectomy (within 24 hours) is associated with better visual outcomes at 9 months, while younger age, poor presenting visual acuity and culture-positive endophthalmitis are associated with poorer visual acuity outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Isolated ischemic ocular cranial nerve palsies (OCNP) involving the 3rd, 4th and 6th cranial nerves (CN) are prevalent conditions in ophthalmic practice. However, it is not clearly established whether such patients are at increased risk of stroke after onset of OCNPs., Methods: Medline, PubMed, Embase and Cochrane Central registers were systematically searched for eligible studies comparing isolated ischemic OCNPs against matched controls on the subsequent development of stroke with at least two years of follow up. Case reports and series were excluded. Appropriate studies were entered for meta-analysis to determine hazard ratios. Search and data extraction was completed on 22 Feb 2021. Random effect models were used to generate pooled hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Three studies were suitable for meta-analysis (total n = 2,756 OCNP cases and 21,239 matched controls). The meta-analysis demonstrated a hazard ratio of 5.96 (4.20-8.46 95% CI) of subsequent stroke after isolated OCNP within the first year. The hazard ratio reduced to 3.27 (2.61-4.10 95% CI) after five years although remains raised at 2.49 (1.53-4.06 95% CI) up to 12 years. The highest risk was demonstrated with 3rd cranial nerve palsies. Two additional studies assessed the risk of stroke with newly diagnosed diabetics and compared OCNPs against lacunar stroke. These studies did not demonstrate a significant increased risk of stroke, although they may be statistically underpowered., Conclusion: Ischemic OCNPs represent a significant risk factor for development of subsequent stroke in a similar magnitude to transient ischemic attack within the first year., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: To assess the agreement and repeatability of horizontal visible iris diameter (HVID) or white-to-white (WTW) measurements between four imaging modalities; combination slit scanning elevation/Placido tomography, infrared biometry, dual rotating scheimpflug camera/Placido tomography, and swept source anterior segment optical coherence tomography (AS-OCT)., Methods: A prospective study of 35 right eyes of healthy volunteers were evaluated using the Orbscan IIz, IOL Master 700, Galilei G2, and DRI Triton OCT devices. The inter-device agreement and repeatability of HVID/WTW measurements for each device were analysed., Results: Mean HVID/WTW values obtained by the Orbscan IIz, IOL Master 700, Galilei G2 and DRI Triton OCT were 11.77 ± 0.40 mm, 12.40 ± 0.43 mm, 12.25 ± 0.42 mm, and 12.42 ± 0.47 mm, respectively. All pairwise comparisons revealed statistically significant differences in mean HVID/WTW measurements (p = <0.01) except for the IOL Master 700-DRI OCT Triton pair (p = 0.56). Mean differences showed that the DRI Triton OCT produced the highest HVID/WTW values, followed by the IOL Master 700, Galilei G2 and Orbscan IIz, respectively. The limits of agreement were large on all device pairs. There was high repeatability for all devices (ICC ≥ 0.980). The highest repeatability was seen in the Galilei G2 (ICC = 0.995) and lowest in the Orbscan IIz (ICC = 0.980)., Conclusions: The four devices exhibit high repeatability, but should not be used interchangeably for HVID/WTW measurements in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Keratoconus progression should be treated with corneal cross-linking (CXL) in a timely manner. This study aimed to investigate patient factors associated with keratoconus progression between time of listing and at time of CXL., Methods: Prospective observational study at a tertiary center. Ninety-six eyes of 96 patients with keratoconus. Demographic, clinical, and tomographic parameters were analyzed to determine the risk factors for keratoconus progression. Analyzed tomographic indices included steepest keratometry, average keratometry, cornea thinnest point, index of surface variance, index of vertical asymmetry, keratoconus index, center keratoconus index, index of height asymmetry, and index of height decentration., Results: A total of 38 eyes (39.6%) were found to have keratoconus progression during an average waiting time of 153 ± 101 days. There were significant differences in preoperative tomographic parameters such as index of surface variance (111.3 ± 36.6 vs. 88.3 ± 31.8; P = 0.002), index of vertical asymmetry (1.1 ± 0.4 vs. 0.9 ± 0.4; P = 0.005), keratoconus index (1.31 ± 0.12 vs. 1.22 ± 0.11; P < 0.001), and index of height decentration (0.16 ± 0.07 vs. 0.11 ± 0.06; P = 0.015) between eyes that progressed and those that remained stable. There were no significant differences in steepest keratometry, average keratometry, cornea thinnest point, and center keratoconus index. Multivariate analysis did not reveal age, presence of atopy/atopic keratoconjunctivitis, eye rubbing, or waiting time to be a significant risk factor for progression; however, Maori ethnicity was a risk factor (odds ratio = 3.89; P = 0.02)., Conclusions: A significant proportion of eyes were found to be progressing while waiting for CXL. A risk stratification score for patients awaiting CXL may reduce the risk of progression.

The trial-to-trial response variability in sensory cortices and the extent to which this variability can be coordinated among cortical units have strong implications for cortical signal processing. Yet, little is known about the relative contributions and dynamics of defined sources to the cortical response variability and their correlations across cortical units. To fill this knowledge gap, here we obtained and analyzed multisite local field potential (LFP) recordings from visual cortex of turtles in response to repeated naturalistic movie clips and decomposed cortical across-trial LFP response variability into three defined sources, namely, input, network, and local fluctuations. We found that input fluctuations dominate cortical response variability immediately following stimulus onset, whereas network fluctuations dominate the response variability in the steady state during continued visual stimulation. Concurrently, we found that the network fluctuations dominate the correlations of the variability during the ongoing and steady-state epochs, but not immediately following stimulus onset. Furthermore, simulations of various model networks indicated that (i) synaptic time constants, leading to oscillatory activity, and (ii) synaptic clustering and synaptic depression, leading to spatially constrained pockets of coherent activity, are both essential features of cortical circuits to mediate the observed relative contributions and dynamics of input, network, and local fluctuations to the cortical LFP response variability and their correlations across recording sites. In conclusion, these results show how a mélange of multiscale thalamocortical circuit features mediate a complex stimulus-modulated cortical activity that, when naively related to the visual stimulus alone, appears disguised as high and coordinated across-trial response variability.

Competing Interests: Nil.

The three-layered visual cortex of turtle is characterized by extensive intracortical axonal projections and receives non-retinotopic axonal projections from lateral geniculate nucleus. What spatiotemporal transformation of visual stimuli into cortical activity arises from such tangle of malleable cortical inputs and intracortical connections? To address this question, we obtained band-pass filtered extracellular recordings of neural activity in turtle dorsal cortex during visual stimulation of the retina. We discovered important spatial and temporal features of stimulus-modulated cortical local field potential (LFP) recordings. Spatial receptive fields span large areas of the visual field, have an intricate internal structure, and lack directional tuning. The receptive field structure varies across recording sites in a distant-dependent manner. Such composite spatial organization of stimulus-modulated cortical activity is accompanied by an equally multifaceted temporal organization. Cortical visual responses are delayed, persistent, and oscillatory. Further, prior cortical activity contributes globally to adaptation in turtle visual cortex. In conclusion, these results demonstrate convoluted spatiotemporal transformations of visual stimuli into stimulus-modulated cortical activity that, at present, largely evade computational frameworks.

Bursts of oscillatory neural activity have been hypothesized to be a core mechanism by which remote brain regions can communicate. Such a hypothesis raises the question to what extent oscillations are coherent across spatially distant neural populations. To address this question, we obtained local field potential (LFP) and membrane potential recordings from the visual cortex of turtle in response to visual stimulation of the retina. The time-frequency analysis of these recordings revealed pronounced bursts of oscillatory neural activity and a large trial-to-trial variability in the spectral and temporal properties of the observed oscillations. First, local bursts of oscillations varied from trial to trial in both burst duration and peak frequency. Second, oscillations of a given recording site were not autocoherent; i.e., the phase did not progress linearly in time. Third, LFP oscillations at spatially separate locations within the visual cortex were more phase coherent in the presence of visual stimulation than during ongoing activity. In contrast, the membrane potential oscillations from pairs of simultaneously recorded pyramidal neurons showed smaller phase coherence, which did not change when switching from black screen to visual stimulation. In conclusion, neuronal oscillations at distant locations in visual cortex are coherent at the mesoscale of population activity, but coherence is largely absent at the microscale of the membrane potential of neurons. NEW & NOTEWORTHY Coherent oscillatory neural activity has long been hypothesized as a potential mechanism for communication across locations in the brain. In this study we confirm the existence of coherent oscillations at the mesoscale of integrated cortical population activity. However, at the microscopic level of neurons, we find no evidence for coherence among oscillatory membrane potential fluctuations. These results raise questions about the applicability of the communication through coherence hypothesis to the level of the membrane potential., (Copyright © 2017 the American Physiological Society.)

The cortex is spontaneously active, even in the absence of any particular input or motor output. During development, this activity is important for the migration and differentiation of cortex cell types and the formation of neuronal connections. In the mature animal, ongoing activity reflects the past and the present state of an animal into which sensory stimuli are seamlessly integrated to compute future actions. Thus, a clear understanding of the organization of ongoing i.e. spontaneous activity is a prerequisite to understand cortex function. Numerous recording techniques revealed that ongoing activity in cortex is comprised of many neurons whose individual activities transiently sum to larger events that can be detected in the local field potential (LFP) with extracellular microelectrodes, or in the electroencephalogram (EEG), the magnetoencephalogram (MEG), and the BOLD signal from functional magnetic resonance imaging (fMRI). The LFP is currently the method of choice when studying neuronal population activity with high temporal and spatial resolution at the mesoscopic scale (several thousands of neurons). At the extracellular microelectrode, locally synchronized activities of spatially neighbored neurons result in rapid deflections in the LFP up to several hundreds of microvolts. When using an array of microelectrodes, the organizations of such deflections can be conveniently monitored in space and time. Neuronal avalanches describe the scale-invariant spatiotemporal organization of ongoing neuronal activity in the brain. They are specific to the superficial layers of cortex as established in vitro, in vivo in the anesthetized rat, and in the awake monkey. Importantly, both theoretical and empirical studies suggest that neuronal avalanches indicate an exquisitely balanced critical state dynamics of cortex that optimizes information transfer and information processing. In order to study the mechanisms of neuronal avalanche development, maintenance, and regulation, in vitro preparations are highly beneficial, as they allow for stable recordings of avalanche activity under precisely controlled conditions. The current protocol describes how to study neuronal avalanches in vitro by taking advantage of superficial layer development in organotypic cortex cultures, i.e. slice cultures, grown on planar, integrated microelectrode arrays (MEA).