Sporadic bovine encephalopathy caused by Chlamydia pecorum secondary to bovine viral diarrhoea virus infection in calves in South Australia.

BACKGROUND: Despite bovine viral diarrhoea virus and Chlamydia pecorum being important endemic diseases of cattle, there are limited reports of theirco-occurrence. CASE REPORT: Several 12-18-week-old, weaned Hereford calves presented with ill-thriftiness and neurological signs on a mixed cattle and sheep farm in South Australia in July 2021. Immune suppression resulting from transient infection with bovine viral diarrhoea virus (BVDV) is implicated in predisposing to infection with Chlamydia pecorum, the causative agent of sporadic bovine encephalopathy (SBE). Chlamydia spp. are difficult to culture in vitro or definitively identify based on current standard molecular based tests. In this case, diagnosis was confirmed by immunohistochemistry. CONCLUSION: To the authors' knowledge, this case report is the first to document BVDV transient infection occurring in conjunction with SBE. Given the current high prevalence of BVDV on Australian farms, such co-infections may have significant future clinical relevance. This case also highlights the need for appropriate tests, such as immunohistochemistry to demonstrate the causative organism in histological lesions and thus reduce the occurrence of false negative diagnosis.

Bedside open tracheostomy in COVID-19 patients - a safe and swift approach.

BACKGROUND: Tracheostomy can be performed as an open surgical procedure, percutaneous, or hybrid and forms an important step in the management of patients infected with coronavirus disease 2019 (COVID-19) requiring weaning from mechanical ventilation. The purpose of this article is to share our experience to performing bedside surgical tracheostomy in COVID-19 patients in a safe and effective manner, whilst minimising the risk of viral transmission, to optimise patient outcomes and reduce risk to healthcare professionals. MATERIAL AND METHODS: As recommended by ENT UK, we prospectively established a COVID Airway Team within the ENT department at Birmingham Heartlands Hospital, consisting of four head and neck consultant surgeons to perform either open-bedside, open-theatre or percutaneous tracheostomy in COVID-19 patients. A specific stepwise method for bedside open surgical tracheostomy was based on ENT UK and British Laryngological Society recommendations. RESULTS: Thirty patients underwent tracheostomy during the study period (14 bedside-open, 5 open-theatre, 11 percutaneous). Mean duration of mechanical intubation prior to bedside-open tracheostomy was 14.5 days. The average time for open-bedside tracheostomy was 9 minutes compared to 31 minutes for open-theatre. There were no significant tracheostomy related complications with bedside-open tracheostomy. No healthcare professional involved reported acute COVID-19 infection. CONCLUSIONS: We describe our effective, safe and swift approach to bedside open tracheostomy during the COVID-19 pandemic. Our experience demonstrated a short mean procedural time, with no tracheostomy-related complications and no reported viral transmission amongst the healthcare members involved.

Body mass index and nutritional intake following Elexacaftor/Tezacaftor/Ivacaftor modulator therapy in adults with cystic fibrosis.

BACKGROUND: Elexacaftor/Tezacaftor/Ivacaftor (ETI) modulator therapy is often associated with increased body mass index (BMI) in people with cystic fibrosis (CF). This is thought to reflect improved clinical stability and increased appetite and nutritional intake. We explored the change in BMI and nutritional intake following ETI modulator therapy in adults with CF. METHODS: Dietary intake, measured with myfood24®, and BMI were collected from adults with CF at baseline and follow-up as part of an observational study. Changes in BMI and nutritional intake in participants who commenced ETI therapy between time points were assessed. To contextualize findings, we also assessed changes in BMI and nutritional intake between study points in a group on no modulators. RESULTS: In the pre and post ETI threapy group (n = 40), BMI significantly increased from 23.0 kg/m2 (IQR 21.4, 25.3) at baseline to 24.6 kg/m2 (IQR 23.0, 26.7) at follow-up (p<0.001), with a median of 68 weeks between time points (range 20-94 weeks) and median duration of ETI therapy was 23 weeks (range 7-72 weeks). There was a significant decrease in energy intake from 2551 kcal/day (IQR 2107, 3115) to 2153 kcal/day (IQR 1648, 2606), p<0.001. In the no modulator group (n = 10), BMI and energy intake did not significantly change between time points (p>0.05), a median of 28 weeks apart (range 20-76 weeks). CONCLUSIONS: These findings tentatively suggest that the increase in BMI with ETI therapy may not simply be attributable to an increase in oral intake. Further exploration into the underlying aetiology of weight gain with ETI therapy is needed.

Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation.

Keratinocytes produce lipids that are critical for the skin barrier, however, little is known about the impact of age on fatty acid (FA) biosynthesis in these cells. We have examined the relationship between keratinocyte FA composition, lipid biosynthetic gene expression, gene promoter methylation and age. Expression of elongase (ELOVL6 and 7) and desaturase (FADS1 and 2) genes was lower in adult versus neonatal keratinocytes, and was associated with lower concentrations of n-7, n-9 and n-10 polyunsaturated FA in adult cells. Consistent with these findings, transient FADS2 knockdown in neonatal keratinocytes mimicked the adult keratinocyte FA profile in neonatal cells. Interrogation of methylation levels across the FADS2 locus (53 genomic sites) revealed differential methylation of 15 sites in neonatal versus adult keratinocytes, of which three hypermethylated sites in adult keratinocytes overlapped with a SMARCA4 protein binding site in the FADS2 promoter.

Measurement of ductions and fields of binocular single vision (BSV): orthoptic practice in the UK and Ireland.

To evaluate the current clinical practice of quantifying ductions and fields of BSV in the UK and Ireland using an online questionnaire. An anonymous online questionnaire with twenty-one questions was distributed in February 2019 via the British and Irish Orthoptic Society (BIOS) members' newsletter. Objectives were to investigate: methods used, frequency of assessment, limiting factors and opinions of importance. Informed consent was gained to include the responses in the study. The data was analyzed using descriptive statistics and Wilcoxon Signed Ranks Testing. The questionnaire was completed by 105 orthoptists. The methods reported to quantify ductions and fields of BSV respectively were: Goldmann (33% and 34%), Aimark (22 and 23%), Lister (7%), Octopus (5 and 4%), Thomson ocular motility analyzer (2 and 3%), Binocular vision analyzer (2%) and no method reported (30% and 32%). The frequency of measuring ductions and fields of BSV per week (median 1-2) was significantly less than the number of patients seen with limited ocular motility per week (median 6-9). The main reasons for never or rarely measuring ductions or fields of BSV were not enough time, no method available and only on selected patients. Respondents indicated that they would measure ductions and fields of BSV more frequently if a quicker portable method was available (median 3-5 times per week). Most agreed that measurements of ductions and fields of BSV are important (89 and 95% respectively). There is no standardized method of quantitively measuring ductions or fields of BSV, with almost a third of respondents not measuring either. Although most orthoptists agreed these measurements are important, they are infrequently performed. The main factors limiting these assessments are insufficient time and lack of a testing method. If a faster portable device was available, orthoptists would measure ductions and fields of BSV more frequently.

Acceptability of childhood screening: a systematic narrative review.

OBJECTIVES: A systematic narrative literature review was undertaken to assess the acceptability of childhood screening interventions to identify factors to consider when planning or modifying childhood screening programs to maximize participation and uptake. STUDY DESIGN: This is a systematic narrative literature review. METHODS: Electronic databases were searched (MEDLINE, EMBASE, PsycINFO via Ovid, CINAHL, and Cochrane Library) to identify primary research studies that assessed screening acceptability. Studies were categorized using an existing theoretical framework of acceptability consisting of seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy. A protocol was developed and registered with PROSPERO (registration no. CRD42018099763) RESULTS: The search identified 4529 studies, and 46 studies met the inclusion criteria. Most studies involved neonatal screening. Programs identified included newborn blood spot screening (n = 22), neonatal hearing screening (n = 13), Duchenne muscular dystrophy screening (n = 4), cystic fibrosis screening (n = 3), screening for congenital heart defects (n = 2), and others (n = 2). Most studies assessed more than one construct of acceptability. The most common constructs identified were affective attitude (how a parent feels about the program) and intervention coherence (parental understanding of the program, and/or the potential consequences of a confirmed diagnosis). CONCLUSIONS: The main acceptability component identified related to parental knowledge and understanding of the screening process, the testing procedure(s), and consent. The emotional impact of childhood screening mostly explored maternal anxiety. Further studies are needed to examine the acceptability of childhood screening across the wider family unit. When planning new (or refining existing) childhood screening programs, it is important to assess acceptability before implementation. This should include assessment of important issues such as information needs, timing of information, and when and where the screening should occur.

The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade.

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.

Correction: Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management.

Prion disease and recommended procedures for flexible endoscope reprocessing - a review of policies worldwide and proposal for a simplified approach.

Several guidelines recommend specific treatments for endoscopes, procedures of quarantine for endoscopes, or additional treatments for the endoscope washer disinfector (EWD) in suspected or confirmed cases of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD) but vary in many details. This study therefore reviewed guidelines on reprocessing flexible endoscopes after use in patients with suspected or confirmed prion disease. In addition, a literature search was performed in Medline on prion, CJD, vCJD, chemical inactivation, transmission healthcare, epidemiology healthcare, concentration tissue human and endoscope. Thus far, no case of CJD or vCJD transmitted by flexible endoscope has been reported. In animals it has been shown that oral uptake of 0.1-5 g of bovine spongiform encephalopathy (BSE)-infected brain homogenate is necessary for transmission. The maximum prion concentration in other tissues (e.g., terminal ileum) is at least 100-fold lower. Automated cleaning of endoscopes alone results in very low total residual protein ≤5.6 mg per duodenoscopes. Recommendations vary between countries, sometimes with additional cleaning, use of alkaline cleaners, no use of cleaners with fixative properties, use of disinfectants without fixative properties or single-use disinfectants. Sodium hydroxide (1 M) and sodium hypochlorite (10,000 and 25,000 mg/L) are very effective in preventing transmission via contaminated wires implanted into animal brains, but their relevance for endoscopes is questionable. Based on circumstantial evidence, it is proposed to consider validated reprocessing as appropriate in the case of delayed suspected prion disease when immediate bedside cleaning, routine use of alkaline cleaners, no fixative agents anywhere prior to disinfection and single use brushes and cleaning solutions can be assured.

Evaluating the impact of information and support for people with nystagmus in the digital age: A patient and carer questionnaire study.

Background: Nystagmus is a disorder of rhythmic, involuntary oscillations of the eyes and can be classified as either infantile or acquired. Whether it occurs in isolation or as a part of other visual or neurological disorders, it causes significant visual dysfunction and problems with social functioning. In this study, we seek to understand ways in which people with nystagmus are currently supported across the UK and identify any geographical variations or disconnects between current practice and best practice, as judged by patients and their carers.Methods: A nationwide, qualitative, cross-sectional, questionnaire study of people with nystagmus and their carers. Recruitment was achieved through specialist clinics, charity events, online advertisements and social media calls. Data was gathered using five, age-appropriate questionnaires which were completed and returned to the research team between November 2016 and August 2018.Results: 184 respondents were included (89 carers, 47 patients aged 4-10 years, 5 aged 11-14 years, 4 aged 15-17 years and 39 > 18 years). Notably, respondents rated social media as the best source of information they have received, even compared with face-to-face consultation with medical professionals. Additionally, only 33% of the respondents had been offered visual impairment support. Notably, patterns of clinical practice and patient experience emerged according to geographical location, particularly provision of initial information and ongoing VI support.Conclusions: This study highlights a significant variation in the support and information received by people in the UK with nystagmus. It also supports the role of charities and increasingly, social media in the provision of patient information. The study also highlights the need for standardized guidelines for the management of patients with nystagmus, particularly with regard to support and information.

Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration.

So far, the investigation in cancer cell lines of the modulation of cancer growth and progression by oxysterols, in particular 27-hydroxycholesterol (27HC), has yielded controversial results. The primary aim of this study was the quantitative evaluation of possible changes in 27HC levels during the different steps of colorectal cancer (CRC) progression in humans. A consistent increase in this oxysterol in CRC mass compared to the tumor-adjacent tissue was indeed observed, but only in advanced stages of progression (TNM stage III), a phase in which cancer has spread to nearby sites. To investigate possible pro-tumor properties of 27HC, its effects were studied in vitro in differentiated CaCo-2 cells. Relatively high concentrations of this oxysterol markedly increased the release of pro-inflammatory interleukins 6 and 8, monocyte chemoattractant protein-1, vascular endothelial growth factor, as well as matrix metalloproteinases 2 and 9. The up-regulation of all these molecules, which are potentially able to favor cancer progression, appeared to be dependent upon a net stimulation of Akt signaling exerted by supra-physiological amounts of 27HC.

Mon2 predicts poor outcome in ST-elevation myocardial infarction.

AIMS: There are limited data on the role of human monocyte subsets in ST-elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI. METHODS: Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase ß (IKKß, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow-up of 46 months. RESULTS: Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43-8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19-7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKß levels were associated with 10-fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6-month follow-up (P < 0.001). CONCLUSIONS: Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.

Termites mitigate the effects of drought in tropical rainforest.

Termites perform key ecological functions in tropical ecosystems, are strongly affected by variation in rainfall, and respond negatively to habitat disturbance. However, it is not known how the projected increase in frequency and severity of droughts in tropical rainforests will alter termite communities and the maintenance of ecosystem processes. Using a large-scale termite suppression experiment, we found that termite activity and abundance increased during drought in a Bornean forest. This increase resulted in accelerated litter decomposition, elevated soil moisture, greater soil nutrient heterogeneity, and higher seedling survival rates during the extreme El Niño drought of 2015-2016. Our work shows how an invertebrate group enhances ecosystem resistance to drought, providing evidence that the dual stressors of climate change and anthropogenic shifts in biotic communities will have various negative consequences for the maintenance of rainforest ecosystems.

UK guidelines on oesophageal dilatation in clinical practice

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.

Cross-disciplinarity in the advance of Antarctic ecosystem research.

The biodiversity, ecosystem services and climate variability of the Antarctic continent and the Southern Ocean are major components of the whole Earth system. Antarctic ecosystems are driven more strongly by the physical environment than many other marine and terrestrial ecosystems. As a consequence, to understand ecological functioning, cross-disciplinary studies are especially important in Antarctic research. The conceptual study presented here is based on a workshop initiated by the Research Programme Antarctic Thresholds - Ecosystem Resilience and Adaptation of the Scientific Committee on Antarctic Research, which focussed on challenges in identifying and applying cross-disciplinary approaches in the Antarctic. Novel ideas and first steps in their implementation were clustered into eight themes. These ranged from scale problems, through risk maps, and organism/ecosystem responses to multiple environmental changes and evolutionary processes. Scaling models and data across different spatial and temporal scales were identified as an overarching challenge. Approaches to bridge gaps in Antarctic research programmes included multi-disciplinary monitoring, linking biomolecular findings and simulated physical environments, as well as integrative ecological modelling. The results of advanced cross-disciplinary approaches can contribute significantly to our knowledge of Antarctic and global ecosystem functioning, the consequences of climate change, and to global assessments that ultimately benefit humankind.

Global biogeographic patterns in bipolar moss species.

A bipolar disjunction is an extreme, yet common, biogeographic pattern in non-vascular plants, yet its underlying mechanisms (vicariance or long-distance dispersal), origin and timing remain poorly understood. Here, combining a large-scale population dataset and multiple dating analyses, we examine the biogeography of four bipolar Polytrichales mosses, common to the Holarctic (temperate and polar Northern Hemisphere regions) and the Antarctic region (Antarctic, sub-Antarctic, southern South America) and other Southern Hemisphere (SH) regions. Our data reveal contrasting patterns, for three species were of Holarctic origin, with subsequent dispersal to the SH, while one, currently a particularly common species in the Holarctic (Polytrichum juniperinum), diversified in the Antarctic region and from here colonized both the Holarctic and other SH regions. Our findings suggest long-distance dispersal as the driver of bipolar disjunctions. We find such inter-hemispheric dispersals are rare, occurring on multi-million-year timescales. High-altitude tropical populations did not act as trans-equatorial 'stepping-stones', but rather were derived from later dispersal events. All arrivals to the Antarctic region occurred well before the Last Glacial Maximum and previous glaciations, suggesting that, despite the harsh climate during these past glacial maxima, plants have had a much longer presence in this southern region than previously thought.

Lipid (per) oxidation in mitochondria: an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease.

Phospholipid oxidation and carotenoid supplementation in Alzheimer's disease patients.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10mg meso-zeaxanthin, 10mg lutein, 2mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=-0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.