Interactions between microsporidia and other members of the microbiome.

The microbiome is the collection of microbes that are associated with a host. Microsporidia are intracellular eukaryotic parasites that can infect most types of animals. In the last decade, there has been much progress to define the relationship between microsporidia and the microbiome. In this review, we cover an increasing number of reports suggesting that microsporidia are common components of the microbiome in both invertebrates and vertebrates. These microsporidia infections can range from mutualistic to pathogenic, causing several physiological phenotypes, including death. Infection with microsporidia often causes a disruption in the normal microbiome, with both increases and decreases of bacterial, fungal, viral, and protozoan species being observed. This impact on the microbiome can occur through upregulation and downregulation of innate immunity as well as morphological changes to tissues that impact interactions with these microbes. Other microbes, particularly bacteria, can inhibit microsporidia and have been exploited to control microsporidia infections. These bacteria can function through regulating immunity, secreting anti-microsporidia compounds, and, in engineered versions, expressing double-stranded RNA targeting microsporidia genes. We end this review by discussing potential future directions to further understand the complex interactions between microsporidia and the other members of the microbiome.

Cep55 regulation of PI3K/Akt signaling is required for neocortical development and ciliogenesis.

Homozygous nonsense mutations in CEP55 are associated with several congenital malformations that lead to perinatal lethality suggesting that it plays a critical role in regulation of embryonic development. CEP55 has previously been studied as a crucial regulator of cytokinesis, predominantly in transformed cells, and its dysregulation is linked to carcinogenesis. However, its molecular functions during embryonic development in mammals require further investigation. We have generated a Cep55 knockout (Cep55-/-) mouse model which demonstrated preweaning lethality associated with a wide range of neural defects. Focusing our analysis on the neocortex, we show that Cep55-/- embryos exhibited depleted neural stem/progenitor cells in the ventricular zone as a result of significantly increased cellular apoptosis. Mechanistically, we demonstrated that Cep55-loss downregulates the pGsk3ß/ß-Catenin/Myc axis in an Akt-dependent manner. The elevated apoptosis of neural stem/progenitors was recapitulated using Cep55-deficient human cerebral organoids and we could rescue the phenotype by inhibiting active Gsk3ß. Additionally, we show that Cep55-loss leads to a significant reduction of ciliated cells, highlighting a novel role in regulating ciliogenesis. Collectively, our findings demonstrate a critical role of Cep55 during brain development and provide mechanistic insights that may have important implications for genetic syndromes associated with Cep55-loss.

Commentary on packing vs non-packing of pilonidal sinus cavities after incision and drainage.

Pilonidal sinus disease (PSD) manifests as an inflammatory skin condition typically emerging within the anal cleft. The prevalence of this disease varies in high income countries. This disease is associated with significant physical and psychosocial distress. Surgery is an option for managing PSD; yet, surgical methods vary, and a universally accepted gold standard approach is lacking, leading to current practices that are diverse and subject to ongoing debate. One such point of contention revolves around the decision to use packing or opt for a non-packing approach following surgery. Mohamedahmed et al (2021) conducted a systematic review to evaluate the comparative outcomes of packing versus non-packing of an abscess cavity following incision and drainage of cutaneous abscess on any part of the body. This commentary aims to critically appraise the methods used within the review by Mohamedahmed et al (2021) and expand upon the findings in the context of treatment and management of PSD.

What defines a chemokine? - The curious case of CXCL17.

Chemotactic cytokines (chemokines) are a group of around 40 small proteins which share a similar protein fold and are well known for their ability to direct the migration of leukocytes to a variety of tissue locations. CXCL17 was the last member of the chemokine family to be assigned and was admitted to the family based on theoretical modelling of the CXCL17 structure and chemotactic activity for monocytes and dendritic cells. Of Interest, CXCL17 expression appears to be restricted to mucosal tissues such as the tongue, stomach and lung, suggestive of specific roles at these locations. A putative CXCL17 receptor, GPR35 was reportedly identified and mice deficient in CXCL17 were generated and characterised. More recently, however, some apparent contradictions regarding aspects of CXCL17 biology have been raised by ourselves and others. Notably, GPR35 appears to be a receptor for the serotonin metabolite 5-hydroxyindoleacetic acid rather than for CXCL17 and modelling of CXCL17 using a variety of platforms fails to identify a chemokine-like fold. In this article, we summarize the discovery of CXCL17 and discuss key papers describing the subsequent characterisation of this protein. Ultimately, we pose the question, 'What defines a chemokine?' (185 words).

ERAP1 Controls the Autoimmune Response against Melanocytes in Psoriasis by Generating the Melanocyte Autoantigen and Regulating Its Amount for HLA-C*06:02 Presentation.

Autoimmune diseases develop when autoantigens activate previously quiescent self-reactive lymphocytes. Gene-gene interaction between certain HLA class I risk alleles and variants of the endoplasmic reticulum aminopeptidase ERAP1 controls the risk for common immune-mediated diseases, including psoriasis, ankylosing spondylitis, and Behçet disease. The functional mechanisms underlying this statistical association are unknown. In psoriasis, HLA-C*06:02 mediates an autoimmune response against melanocytes by autoantigen presentation. Using various genetically modified cell lines together with an autoreactive psoriatic TCR in a TCR activation assay, we demonstrate in this study that in psoriasis, ERAP1 generates the causative melanocyte autoantigen through trimming N-terminal elongated peptide precursors to the appropriate length for presentation by HLA-C*06:02. An ERAP1 risk haplotype for psoriasis produced the autoantigen much more efficiently and increased HLA-C expression and stimulation of the psoriatic TCR by melanocytes significantly more than a protective haplotype. Compared with the overall HLA class I molecules, cell surface expression of HLA-C decreased significantly more upon ERAP1 knockout. The combined upregulation of ERAP1 and HLA-C on melanocytes in psoriasis lesions emphasizes the pathogenic relevance of their interaction in patients. We conclude that in psoriasis pathogenesis, the increased generation of an ERAP1-dependent autoantigen by an ERAP1 risk haplotype enhances the likelihood that autoantigen presentation by HLA-C*06:02 will exceed the threshold for activation of potentially autoreactive T cells, thereby triggering CD8+ T cell-mediated autoimmune disease. These data identify ERAP1 function as a central checkpoint and promising therapeutic target in psoriasis and possibly other HLA class I-associated diseases with a similar genetic predisposition.

Diffuse Correlation Spectroscopy: A Review of Recent Advances in Parallelisation and Depth Discrimination Techniques.

Diffuse correlation spectroscopy is a non-invasive optical modality used to measure cerebral blood flow in real time, and it has important potential applications in clinical monitoring and neuroscience. As such, many research groups have recently been investigating methods to improve the signal-to-noise ratio, imaging depth, and spatial resolution of diffuse correlation spectroscopy. Such methods have included multispeckle, long wavelength, interferometric, depth discrimination, time-of-flight resolution, and acousto-optic detection strategies. In this review, we exhaustively appraise this plethora of recent advances, which can be used to assess limitations and guide innovation for future implementations of diffuse correlation spectroscopy that will harness technological improvements in the years to come.

Effectiveness of zinc therapy for the treatment of pressure ulcers.

Pressure ulcers are a significant burden in healthcare settings, impacting patients' lives and incurring substantial costs. Nutrition, including the micronutrient zinc, plays a role in wound healing. However, controversy exists regarding zinc supplementation for pressure ulcer management. Further research is needed to determine the efficacy, optimal dosages, and safety of oral zinc supplementation. This commentary provides a critical appraisal of the systematic review conducted by Song et al (2020), which evaluates the efficacy of zinc therapy in the treatment of pressure sores, focusing on the implementation of the nutritional recommendations in context to practice.

Cognitive frailty in older adults with diabetes: prevalence and risk factors.

In older adults living with diabetes, there is a higher prevalence of frailty and a greater risk of cognitive impairment. Cognitive frailty is defined by the presence of both and is associated with an increased risk of mortality. A systematic review was undertaken to estimate the prevalence of cognitive frailty in community-dwelling older adults living with diabetes and associated risk factors. This commentary critically appraises the review and explores the implications of the findings for community practice.

Repositioning for pressure injury prevention in adults: a commentary on a Cochrane review.

Repositioning is regarded as an important intervention to prevent the development of pressure injuries in patients who are immobile. However, there is uncertainty as to the optimal regimen in terms of frequency and method of repositioning. This commentary summarises and critically appraises a Cochrane systematic review that assessed the clinical and costeffectiveness of different repositioning regimens on the prevention of pressure injuries in adults in any setting.

Advancing pressure ulcer prevention: evaluating the impact of patient and lay carer education.

Decubitus ulcers, also known as bed ulcers or pressure ulcers, result from prolonged pressure on the skin, with contributing factors such as shear forces, friction and excessive moisture. Pressure ulcers have significant physical, social and psychological consequences for patients and impose a substantial financial burden on healthcare providers. Patient and caregiver education has been suggested as a potential approach for preventing pressure ulcers. In order to investigate the potential preventive impact, O'Connor et al (2021) conducted a Cochrane systematic review. Their study aimed to assess the effectiveness of educational interventions for patients and caregivers in preventing pressure ulcers. This commentary aims to critically appraise the methods used within the Cochrane systematic review by O'Connor et al (2022) and expand on the findings in the context of clinical practice.

Wound cleansing and care in treating leg ulcers: a commentary on a Cochrane systematic review.

Leg ulcers pose a significant challenge to healthcare services, requiring effective wound cleansing strategies to promote healing and prevent complications. Large amounts of nursing time is spent managing patients with venous leg ulcers (VLUs), with an average appointment time of approximately 30 minutes. Yet, there is a lack of clear guidance for the treatment of VLUs, with nurses adopting a wide range of cleansing practices. This commentary provides an overview of existing evidence on wound cleansing and care in treating leg ulcers, for the benefit of healthcare professionals working within clinical practice.

Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG).

Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.

A potent virucidal activity of functionalized TiO2 nanoparticles adsorbed with flavonoids against SARS-CoV-2.

The coronavirus SARS-CoV-2 has caused a pandemic with > 550 millions of cases and > 6 millions of deaths worldwide. Medical management of COVID-19 relies on supportive care as no specific targeted therapies are available yet. Given its devastating effects on the economy and mental health, it is imperative to develop novel antivirals. An ideal candidate will be an agent that blocks the early events of viral attachment and cell entry, thereby preventing viral infection and spread. This work reports functionalized titanium dioxide (TiO2)-based nanoparticles adsorbed with flavonoids that block SARS-CoV-2 entry and fusion. Using molecular docking analysis, two flavonoids were chosen for their specific binding to critical regions of the SARS-CoV-2 spike glycoprotein that interacts with the host cell angiotensin-converting enzyme-2 (ACE-2) receptor. These flavonoids were adsorbed onto TiO2 functionalized nanoparticles (FTNP). This new nanoparticulate compound was assayed in vitro against two different coronaviruses; HCoV 229E and SARS-CoV-2, in both cases a clear antiviral effect was observed. Furthermore, using a reporter-based cell culture model, a potent antiviral activity is demonstrated. The adsorption of flavonoids to functionalized TiO2 nanoparticles induces a ~ threefold increase of that activity. These studies also indicate that FTNP interferes with the SARS-CoV-2 spike, impairing the cell fusion mechanism. KEY POINTS/HIGHLIGHTS: • Unique TiO2 nanoparticles displaying flavonoid showed potent anti-SARS-CoV-2 activity. • The nanoparticles precisely targeting SARS-CoV-2 were quantitatively verified by cell infectivity in vitro. • Flavonoids on nanoparticles impair the interactions between the spike glycoprotein and ACE-2 receptor.

N,N-dimethyltryptamine and Amazonian ayahuasca plant medicine.

OBJECTIVE: Reports have indicated possible uses of ayahuasca for the treatment of conditions including depression, addictions, post-traumatic stress disorder, anxiety and specific psychoneuroendocrine immune system pathologies. The article assesses potential ayahuasca and N,N-dimethyltryptamine (DMT) integration with contemporary healthcare. The review also seeks to provide a summary of selected literature regarding the mechanisms of action of DMT and ayahuasca; and assess to what extent the state of research can explain reports of unusual phenomenology. DESIGN: A narrative review. RESULTS: Compounds in ayahuasca have been found to bind to serotonergic receptors, glutaminergic receptors, sigma-1 receptors, trace amine-associated receptors, and modulate BDNF expression and the dopaminergic system. Subjective effects are associated with increased delta and theta oscillations in amygdala and hippocampal regions, decreased alpha wave activity in the default mode network, and stimulations of vision-related brain regions particularly in the visual association cortex. Both biological processes and field of consciousness models have been proposed to explain subjective effects of DMT and ayahuasca, however, the evidence supporting the proposed models is not sufficient to make confident conclusions. Ayahuasca plant medicine and DMT represent potentially novel treatment modalities. CONCLUSIONS: Further research is required to clarify the mechanisms of action and develop treatments which can be made available to the general public. Integration between healthcare research institutions and reputable practitioners in the Amazon is recommended.

The prevalence of mental health conditions in healthcare workers during and after a pandemic: Systematic review and meta-analysis.

AIMS: This review aims to explore the prevalence and incidence rates of mental health conditions in healthcare workers during and after a pandemic outbreak and which factors influence rates. BACKGROUND: Pandemics place considerable burden on care services, impacting on workers' health and their ability to deliver services. We systematically reviewed the prevalence and incidence of mental health conditions in care workers during pandemics. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of MEDLINE, Embase, Cochrane Library and PsychINFO for cohort, cross-sectional and case-control studies were undertaken on the 31 March 2020 (from inception to 31 March 2020). REVIEW METHODS: Only prevalence or incidence rates for mental health conditions from validated tools were included. Study selection, data extraction and quality assessment were carried out by two reviewers. Meta-analyses and subgroup analyses were produced for pandemic period (pre- and post), age, country income, country, clinical setting for major depression disorder (MDD), anxiety disorder and post-traumatic stress disorder (PTSD). RESULTS: No studies of incidence were found. Prevalence estimates showed that the most common mental health condition was PTSD (21.7%) followed by anxiety disorder (16.1%), MDD (13.4%) and acute stress disorder (7.4%) (low risk of bias). For symptoms of these conditions there was substantial variation in the prevalence estimates for depression (95% confidence interval [CI]:31.8%; 60.5%), anxiety (95% CI:34.2%; 57.7%) and PTSD symptoms (95% CI,21.4%; 65.4%) (moderate risk of bias). Age, level of exposure and type of care professional were identified as important moderating factors. CONCLUSION: Mental disorders affect healthcare workers during and after infectious disease pandemics, with higher proportions experiencing symptoms. IMPACT: This review provides prevalence estimates of mental health conditions during and after a pandemic which could be used to inform service staffing impact and formulation of preventative strategies, by identifying clinical populations who may be at high risk of developing mental health symptoms and conditions.

Scoping review of the use of virtual reality in intensive care units.

BACKGROUND: A wide range of reviews have demonstrated the effectiveness and tolerability of Virtual Reality (VR) in a range of clinical areas and subpopulations. However, no previous review has explored the current maturity, acceptability, tolerability, and effectiveness of VR with intensive care patients. AIMS: To identify the range of uses of VR for intensive care patients, classify their current phase of development, effectiveness, acceptability, and tolerability. METHODS: A scoping review was conducted. A multi-database search was undertaken (inception to January 2021). Any type of study which examined the use of VR with the target application population of intensive care patients were included. Screening, data extraction, and assessment of quality were undertaken by a single reviewer. A meta-analysis and a descriptive synthesis were undertaken. RESULTS: Six hundred and forty-seven records were identified, after duplicate removal and screening 21 studies were included (weak quality). The majority of studies for relaxation, delirium, and Post Traumatic Stress Disorder (PTSD) were at the early stages of assessing acceptability, tolerability, and initial clinical efficacy. Virtual Reality for relaxation and delirium were well-tolerated with completion rates of target treatment of 73.6%, (95% CI:51.1%-96%, I2  = 98.52%) 52.7% (95% CI:52.7%-100%, I2  = 96.8%). The majority of reasons for non-completion were due to external clinical factors. There were some potential benefits demonstrated for the use of VR for relaxation, delirium, and sleep. CONCLUSION: Virtual Reality for intensive care is a new domain of research with the majority of areas of application being in the early stages of development. There is great potential for the use of VR in this clinical environment. Further robust assessment of effectiveness is required before any clinical recommendations can be made. RELEVANCE TO CLINICAL PRACTICE: Virtual reality for ICU patients is in its infancy and is not at a stage where it should be used as routine practice. However, there is early evidence to suggest that virtual reality interventions have good acceptability and tolerability in intensive care patients for relaxation, delirium, and improving sleep.

Interventions for the treatment and prevention of pressure ulcers.

Pressure ulcers can affect multiple aspects of an individual's life. Though preventable, pressure ulcers place a substantial economic burden on healthcare services. Countries around the world have set pressure ulcer prevention and treatment as a high priority. National Clinical Guidelines recommend a wide range of preventative and curative treatments. However, there is still much uncertainty regarding the effectiveness of preventative and curative treatments. This overview of systematic reviews aims to describe the findings of 15 Cochrane reviews on the treatment and prevention of pressure ulcers included in a previous umbrella review and to expand upon their findings in the context of clinical practice.

Simulation of statistically accurate time-integrated dynamic speckle patterns in biomedical optics.

The simulation of statistically accurate time-integrated dynamic speckle patterns using a physics-based model that accounts for spatially varying sample properties is yet to be presented in biomedical optics. In this Letter, we propose a solution to this important problem based on the Karhunen-Loève expansion of the electric field and apply our method to the formalisms of both laser speckle contrast imaging and diffuse correlation spectroscopy. We validate our technique against solutions for speckle contrast for different forms of homogeneous field and also show that our method can readily be extended to cases with spatially varying sample properties.

The genome sequence of the grape phylloxera provides insights into the evolution, adaptation, and invasion routes of an iconic pest.

BACKGROUND: Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150 years, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture. RESULTS: Using a combination of genome, RNA, and population resequencing, we found grape phylloxera showed high duplication rates since its common ancestor with aphids, but similarity in most metabolic genes, despite lacking obligate nutritional symbioses and feeding from parenchyma. Similarly, no enrichment occurred in development genes in relation to viviparity. However, phylloxera evolved > 2700 unique genes that resemble putative effectors and are active during feeding. Population sequencing revealed the global invasion began from the upper Mississippi River in North America, spread to Europe and from there to the rest of the world. CONCLUSIONS: The grape phylloxera genome reveals genetic architecture relative to the evolution of nutritional endosymbiosis, viviparity, and herbivory. The extraordinary expansion in effector genes also suggests novel adaptations to plant feeding and how insects induce complex plant phenotypes, for instance galls. Finally, our understanding of the origin of this invasive species and its genome provide genetics resources to alleviate rootstock bottlenecks restricting the advancement of viticulture.

Correction to: The genome sequence of the grape phylloxera provides insights into the evolution, adaptation, and invasion routes of an iconic pest.

An amendment to this paper has been published and can be accessed via the original article.