A review of neuro-ophthalmic sequelae following COVID-19 infection and vaccination

BackgroundIt has become increasingly clear that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect most organs in the human body, including the neurologic and ophthalmic systems. Vaccination campaigns have been developed at rapid pace around the world to protect the population from the fast-mutating virus. This review seeks to summarise current knowledge of the neuro-ophthalmic manifestations of both COVID-19 infection and vaccination.Evidence acquisitionElectronic searches for published literature were conducted using EMBASE and MEDLINE on the 30th of July 2023. The search strategy comprised of controlled vocabulary and free-text synonyms for the following terms in various combinations: “coronavirus, COVID-19, SARS-CoV-2, 2019-nCoV, vaccination, vaccine, immunisation and neuro-ophthalmology”. No time range limits were set for the literature search. Published English abstracts for articles written in a different language were screened if available.ResultsA total of 54 case reports and case series were selected for use in the final report. 34 articles documenting neuro-ophthalmic manifestations following COVID-19 infection and 20 articles with neuro-ophthalmic complications following COVID-19 vaccination were included, comprising of 79 patients in total. The most commonly occurring condition was optic neuritis, with 25 cases following COVID-19 infection and 27 cases following vaccination against COVID-19.ConclusionsThe various COVID-19 vaccines that are currently available are part of the global effort to protect the most vulnerable of the human population. The incidence of neuro-ophthalmic consequences following infection with COVID-19 is hundred-folds higher and associated with more harrowing systemic effects than vaccination against the virus

Sleep duration and patterns in Chinese older adults: A comprehensive meta-analysis

This meta-analysis examined the mean sleep duration and patterns in Chinese older adult population. A literature search was systematically conducted covering major English (PubMed, Embase and PsycINFO) and Chinese (Chinese National Knowledge Infrastructure (CNKI), WanFang and SinoMed) databases. Data in studies with the mean and standard deviation of sleep duration and/or the proportion of short and long sleep durations in Chinese older adults were extracted and pooled using random-effects models. Subgroup analyses were conducted according to gender, region, area, survey time and sample size. A total of 36 studies with 150,616 subjects were included for analyses. The pooled mean sleep duration of 21 studies with available data was 6.82 hours/day (95% CI: 6.59–7.05 hours/day). The estimated proportions of sleep duration \u3c5 hours/day, \u3c6 hours/day, \u3c7 hours/day were 18.8% (95% CI: 1.7%–35.9%), 26.7% (95% CI: 19.7%–33.7%) and 42.3% (95% CI: 34.8%–49.8%), respectively. The pooled proportions for long sleepers were 22.6% (95% CI: 13.9%–31.4%) (\u3e8 hours/day) and 17.6% (95% CI: 12.4%–22.9%) (\u3e9 hours/day). Given the adverse effects of unhealthy sleep patterns, health professionals should pay more attention to sleep patterns in this population in China

A Microbiome-Based Index for Assessing Skin Health and Treatment Effects for Atopic Dermatitis in Children.

A quantitative and objective indicator for skin health via the microbiome is of great interest for personalized skin care, but differences among skin sites and across human populations can make this goal challenging. A three-city (two Chinese and one American) comparison of skin microbiota from atopic dermatitis (AD) and healthy pediatric cohorts revealed that, although city has the greatest effect size (the skin microbiome can predict the originated city with near 100% accuracy), a microbial index of skin health (MiSH) based on 25 bacterial genera can diagnose AD with 83 to ∼95% accuracy within each city and 86.4% accuracy across cities (area under the concentration-time curve [AUC], 0.90). Moreover, nonlesional skin sites across the bodies of AD-active children (which include shank, arm, popliteal fossa, elbow, antecubital fossa, knee, neck, and axilla) harbor a distinct but lesional state-like microbiome that features relative enrichment of Staphylococcus aureus over healthy individuals, confirming the extension of microbiome dysbiosis across body surface in AD patients. Intriguingly, pretreatment MiSH classifies children with identical AD clinical symptoms into two host types with distinct microbial diversity and treatment effects of corticosteroid therapy. These findings suggest that MiSH has the potential to diagnose AD, assess risk-prone state of skin, and predict treatment response in children across human populations.IMPORTANCE MiSH, which is based on the skin microbiome, can quantitatively assess pediatric skin health across cohorts from distinct countries over large geographic distances. Moreover, the index can identify a risk-prone skin state and compare treatment effect in children, suggesting applications in diagnosis and patient stratification

Probing the mechanisms of electron capture dissociation mass spectrometry with nitrated peptides

Previously we have shown that the presence of 3-nitrotyrosine within a peptide sequence severely depletes the peptide backbone fragments typically observed following electron capture dissociation (ECD) mass spectrometry. Instead, ECD of nitrated peptides is characterised by abundant losses of small neutrals (hydroxyl radicals, water and ammonia). Here, we investigate the origin of ammonia loss by comparing the ECD behaviour of lysine- and arginine-containing nitrated peptides, and their N-acetylated counterparts, and nitrated peptides containing no basic amino acid residues. The results reveal that ammonia loss derives from the N-terminus of the peptides, however, the key finding of this work is the insight provided into the hierarchy of various proposed ECD mechanisms: the Utah-Washington mechanism, the electron predator mechanism and the Oslo mechanism

Evolutionary Conservation of the PA-X Open Reading Frame in Segment 3 of Influenza A Virus

PA-X is a fusion protein of influenza A virus encoded in part from a +1 frameshifted X open reading frame (X-ORF) in segment 3. We show that the X-ORFs of diverse influenza A viruses can be divided into two groups that differ in selection pressure and likely function, reflected in the presence of an internal stop codon and a change in synonymous diversity. Notably, truncated forms of PA-X evolved convergently in swine and dogs, suggesting a strong species-specific effect

Bunyamwera orthobunyavirus glycoprotein precursor is processed by cellular signal peptidase and signal peptide peptidase

This study was supported by Wellcome Trust Grant 099220/B/12/Z (to R.M.E.) and Grant 094476/Z/10/Z that funded the purchase of the TripleTOF 5600 mass spectrometer at the Biomedical Sciences Research Complex (BSRC) of University of St. Andrews.Bunyamwera virus (BUNV) is the prototype of the Orthobunyavirus genus and Bunyaviridae family that contains important human and animal pathogens. The cleavage mechanism of orthobunyavirus glycoprotein precursor (GPC) and the host proteases involved have not been clarified. Here we found that NSm and Gc contain their own internal signal peptides, which mediate the GPC cleavage by host signal peptidase and signal peptide peptidase (SPP). Furthermore, the NSm domain-I plays an important postcleavage role in cell fusion. Our data clarified the implication of host proteases in the processing of the orthobunyavirus GPC. This work identifies SPP as a potential intervention target, and the knowledge we gained will benefit preventive strategies against other orthobunyavirus infections.PostprintPeer reviewe

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia

Background: Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in persons who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions may reduce the risk of VAP in these patients. Objectives: To assess the effects of OHC on the incidence of VAP in critically ill patients receiving mechanical ventilation in intensive care units (ICUs) in hospitals. Search methods: We searched the Cochrane Oral Health Group's Trials Register (to 14 January 2013), CENTRAL (The Cochrane Library 2012, Issue 12), MEDLINE (OVID) (1946 to 14 January 2013), EMBASE (OVID) (1980 to 14 January 2013), LILACS (BIREME) (1982 to 14 January 2013), CINAHL (EBSCO) (1980 to 14 January 2013), Chinese Biomedical Literature Database (1978 to 14 January 2013), China National Knowledge Infrastructure (1994 to 14 January 2013), Wan Fang Database (January 1984 to 14 January 2013), OpenGrey and ClinicalTrials.gov (to 14 January 2013). There were no restrictions regarding language or date of publication. Selection criteria: We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation. Data collection and analysis: Two review authors independently assessed all search results, extracted data and undertook risk of bias. We contacted study authors for additional information. Trials with similar interventions and outcomes were pooled reporting odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes using random-effects models unless there were fewer than four studies. Main results: Thirty-five RCTs (5374 participants) were included. Five trials (14%) were assessed at low risk of bias, 17 studies (49%) were at high risk of bias, and 13 studies (37%) were assessed at unclear risk of bias in at least one domain. There were four main comparisons: chlorhexidine (CHX mouthrinse or gel) versus placebo/usual care, toothbrushing versus no toothbrushing, powered versus manual toothbrushing and comparisons of oral care solutions. There is moderate quality evidence from 17 RCTs (2402 participants, two at high, 11 at unclear and four at low risk of bias) that CHX mouthrinse or gel, as part of OHC, compared to placebo or usual care is associated with a reduction in VAP (OR 0.60, 95% confidence intervals (CI) 0.47 to 0.77, P < 0.001, I2 = 21%). This is equivalent to a number needed to treat (NNT) of 15 (95% CI 10 to 34) indicating that for every 15 ventilated patients in intensive care receiving OHC including chlorhexidine, one outcome of VAP will be prevented. There is no evidence of a difference between CHX and placebo/usual care in the outcomes of mortality (OR 1.10, 95% CI 0.87 to 1.38, P = 0.44, I2 = 2%, 15 RCTs, moderate quality evidence), duration of mechanical ventilation (MD 0.09, 95% CI -0.84 to 1.01 days, P = 0.85, I2 = 24%, six RCTs, moderate quality evidence), or duration of ICU stay (MD 0.21, 95% CI -1.48 to 1.89 days, P = 0.81, I2 = 9%, six RCTs, moderate quality evidence). There was insufficient evidence to determine whether there is a difference between CHX and placebo/usual care in the outcomes of duration of use of systemic antibiotics, oral health indices, microbiological cultures, caregivers preferences or cost. Only three studies reported any adverse effects, and these were mild with similar frequency in CHX and control groups. From three trials of children aged from 0 to 15 years (342 participants, moderate quality evidence) there is no evidence of a difference between OHC with CHX and placebo for the outcomes of VAP (OR 1.07, 95% CI 0.65 to 1.77, P = 0.79, I2 = 0%), or mortality (OR 0.73, 95% CI 0.41 to 1.30, P = 0.28, I2 = 0%), and insufficient evidence to determine the effect on the outcomes of duration of ventilation, duration of ICU stay, use of systemic antibiotics, plaque index, microbiological cultures or adverse effects, in children. Based on four RCTs (828 participants, low quality evidence) there is no evidence of a difference between OHC including toothbrushing (- CHX) compared to OHC without toothbrushing (- CHX) for the outcome of VAP (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24, I2 = 64%) and no evidence of a difference for mortality (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I2 = 0%, four RCTs, moderate quality evidence). There is insufficient evidence to determine whether there is a difference due to toothbrushing for the outcomes of duration of mechanical ventilation, duration of ICU stay, use of systemic antibiotics, oral health indices, microbiological cultures, adverse effects, caregivers preferences or cost. Only one trial compared use of a powered toothbrush with a manual toothbrush providing insufficient evidence to determine the effect on any of the outcomes of this review. A range of other oral care solutions were compared. There is some weak evidence that povidone iodine mouthrinse is more effective than saline in reducing VAP (OR 0.35, 95% CI 0.19 to 0.65, P = 0.0009, I2 = 53%) (two studies, 206 participants, high risk of bias). Due to the variation in comparisons and outcomes among the trials in this group there is insufficient evidence concerning the effects of other oral care solutions on the outcomes of this review. Authors' conclusions: Effective OHC is important for ventilated patients in intensive care. OHC that includes either chlorhexidine mouthwash or gel is associated with a 40% reduction in the odds of developing ventilator-associated pneumonia in critically ill adults. However, there is no evidence of a difference in the outcomes of mortality, duration of mechanical ventilation or duration of ICU stay. There is no evidence that OHC including both CHX and toothbrushing is different from OHC with CHX alone, and some weak evidence to suggest that povidone iodine mouthrinse is more effective than saline in reducing VAP. There is insufficient evidence to determine whether powered toothbrushing or other oral care solutions are effective in reducing VAP

Error, reproducibility and sensitivity : a pipeline for data processing of Agilent oligonucleotide expression arrays

Background Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2% of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log2 units ( 6% of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells