Understanding the lived experience research priorities for improving health-related quality of life in people living with HIV with cognitive impairment.

BACKGROUND: People living with HIV experience higher rates of cognitive impairment (CI), and at younger ages, than the general population. These individuals report poor health-related quality of life (HRQL), however, interventions aimed at assisting people living with HIV to live well with CI do not currently exist and represent an important un-met need in this population. OBJECTIVE: This study aimed to identify the lived experience research priorities for improving HRQL and identify interventions to support priority areas. METHODS: A Research Advisory Group was established with 15 lived experience, academic, healthcare, and third sector professionals. Additionally, two semi-structured focus groups were undertaken, with health and third sector professionals and people living with HIV with CI. Participants were asked to rank factors impacting HRQL, identified in prior research, in terms of priority and intervention development. Findings were analysed using a combination of conventional and summative content analysis. Study findings were feedback to our Research Advisory Group. RESULTS: Five people living with HIV with CI, recruited through third sector agencies [Male 80%; median age 59 (range 56-78); White British 60%; homosexual 60%], and three healthcare and third sector participants (66% third sector professionals from two local HIV charities; 33% HIV-specific clinical psychologist) took part in two focus groups and ranked interventions targeting improvement in physical function, social connectedness, cognition and perceived control over cognitive health as priority areas. Findings were then fed back to the Research Advisory Group who recommended the development of an illness-specific cognitive rehabilitation programme and improved information provision as important avenues for intervention development. CONCLUSION: Given the absence of meaningful patient and public involvement, intervention, and support guidelines for people living with HIV with CI, this provides a roadmap for future research in this important and growing area of HIV clinical care.

UCHL1-dependent control of Hypoxia-Inducible Factor Transcriptional Activity during Liver Fibrosis.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most  chronic liver diseases.  At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic.  HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation, however, the cellular targets of its deubiquitinating activity are poorly defined.     Here we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis.  HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease.  Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies.

Overexpression of oilseed rape trehalose-6-phosphate synthesis gene BnaC02.TPS8 confers sensitivity to low nitrogen and high sucrose-induced anthocyanin accumulation in Arabidopsis.

MAIN CONCLUSION: Overexpression of BnaC02.TPS8 increased low N and high sucrose-induced anthocyanin accumulation. Anthocyanin plays a crucial role in safeguarding photosynthetic tissues against high light, UV radiation, and oxidative stress. Their accumulation is triggered by low nitrogen (N) stress and elevated sucrose levels in Arabidopsis. Trehalose-6-phosphate (T6P) serves as a pivotal signaling molecule, sensing sucrose availability, and carbon (C) metabolism. However, the mechanisms governing the regulation of T6P synthase (TPS) genes responsible for anthocyanin accumulation under conditions of low N and high sucrose remain elusive. In a previous study, we demonstrated the positive impact of a cytoplasm-localized class II TPS protein 'BnaC02.TPS8' on photosynthesis and seed yield improvement in Brassica napus. The present research delves into the biological role of BnaC02.TPS8 in response to low N and high sucrose. Ectopic overexpression of BnaC02.TPS8 in Arabidopsis seedlings resulted in elevated shoot T6P levels under N-sufficient conditions, as well as an increased carbon-to-nitrogen (C/N) ratio, sucrose accumulation, and starch storage under low N conditions. Overexpression of BnaC02.TPS8 in Arabidopsis heightened sensitivity to low N stress and high sucrose levels, accompanied by increased anthocyanin accumulation and upregulation of genes involved in flavonoid biosynthesis and regulation. Metabolic profiling revealed increased levels of intermediate products of carbon metabolism, as well as anthocyanin and flavonoid derivatives in BnaC02.TPS8-overexpressing Arabidopsis plants under low N conditions. Furthermore, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses demonstrated that BnaC02.TPS8 interacts with both BnaC08.TPS9 and BnaA01.TPS10. These findings contribute to our understanding of how TPS8-mediated anthocyanin accumulation is modulated under low N and high sucrose conditions.

Proteomics reveals the significance of vacuole Pi transporter in the adaptability of Brassica napus to Pi deprivation.

Vacuolar Pi transporters (VPTs) have recently been identified as important regulators of cellular Pi status in Arabidopsis thaliana and Oryza sativa. In the oil crop Brassica napus, BnA09PHT5;1a and BnC09PHT5;1a are two homologs of AtPHT5;1, the vacuolar Pi influx transporter in Arabidopsis. Here, we show that Pi deficiency induces the transcription of both homologs of PHT5;1a genes in B. napus leaves. Brassica PHT5;1a double mutants (DM) had smaller shoots and higher cellular Pi concentrations than wild-type (WT, Westar 10), suggesting the potential role of BnPHT5;1a in modulating cellular Pi status in B. napus. A proteomic analysis was performed to estimate the role of BnPHT5;1a in Pi fluctuation. Results show that Pi deprivation disturbs the abundance of proteins in the physiological processes involved in carbohydrate metabolism, response to stimulus and stress in B. napus, while disruption of BnPHT5;1a genes may exacerbate these processes. Besides, the processes of cell redox homeostasis, lipid metabolic and proton transmembrane transport are supposed to be unbalanced in BnPHT5;1a DM under the -Pi condition. Noteworthy, disruption of BnPHT5;1a genes severely alters the abundance of proteins related to ATP biosynthesis, and proton/inorganic cation transmembrane under normal Pi condition, which might contribute to B. napus growth limitations. Additionally, seven new protein markers of Pi homeostasis are identified in B. napus. Taken together, this study characterizes the important regulatory role of BnPHT5;1a genes as vacuolar Pi influx transporters in Pi homeostasis in B. napus.

Overcoming barriers to equality, diversity, inclusivity, and sense of belonging in healthcare education: the Underrepresented Groups' Experiences in Osteopathic Training (UrGEnT) mixed methods study.

BACKGROUND: Individuals from minority groups have historically faced social injustices. Those from underrepresented groups have been less likely to access both healthcare services and higher education. Little is known about the experiences of underrepresented students during their undergraduate studies in osteopathy in the UK. The aim of this project was to explore awareness of cultural diversity and beliefs about patients from underrepresented groups in current osteopathic educational environments and evaluate students' preparedness to manage patients from diverse groups. The project also aimed to investigate the educational experiences of students from underrepresented backgrounds during their training and their opinions on changes that could support better levels of recruitment and achievement. The findings were discussed with stakeholders in interactive workshops with the aim to develop recommendations for action and change. METHODS: A transformative action research paradigm informed this mixed methods project. It included: 1/ a survey of students from all seven osteopathic educational providers in the UK using the Multidimensional Cultural Humility Scale (MCHS); 2/ a series of focus groups with students from underrepresented groups (women, students with disabilities, students from minority ethnic backgrounds, and students identifying as LGBTQIA+); and 3/ a workshop forum to discuss findings. RESULTS: A total of 202 participants completed the MCHS and demographic questionnaire and seven focus groups were conducted. A model was developed to describe participants' training experiences comprising two main themes: institutional contextual obstacles (with four sub-themes) and underrepresented students' conceptual understanding of Equity, Diversity and Inclusion (EDI). Recommendations for change identified in the workshops were based on three topics: institutions, staff, and students. CONCLUSION: Our findings confirm conclusions from other institutions that staff education is urgently needed to create and maintain equitable, inclusive environments in osteopathic educational institutions in the UK to support all students, particularly those from underrepresented groups. Institutional EDI processes and policies also need to be clarified or modified to ensure their usefulness, accessibility, and implementation.

Trade-offs between root-secreted acid phosphatase and root morphology traits, and their contribution to phosphorus acquisition in Brassica napus.

Oilseed rape (Brassica napus) is one of the most important oil crops in the world and shows sensitivity to low phosphorus (P) availability. In many soils, organic P (Po) is the main component of the soil P pool. Po must be mineralised to Pi through phosphatases, and then taken up by plants. However, the relationship between root-secreted acid phosphatases (APase) and root morphology traits, two important P-acquisition strategies in response to P deficiency, is unclear among B. napus genotypes. This study aimed to understand their relationship and how they affect P acquisition, which is crucial for the sustainable utilisation of agricultural P resources. This study showed significant genotypic variations in root-secreted APase activity per unit root fresh weight (SAP) and total root-secreted APase activity per plant (total SAP) among 350 B. napus genotypes. Seed yield was positively correlated with total SAP but not significantly correlated with SAP. Six root traits of 18 B. napus genotypes with contrasting root biomass were compared under normal Pi, low Pi and Po. Genotypes with longer total root length (TRL) reduced SAP, but those with shorter TRL increased SAP under P deficiency. Additionally, TRL was important in P-acquisition under three P treatments, and total SAP was also important in P-acquisition under Po treatment. In conclusion, trade-offs existed between the two P-acquisition strategies among B. napus genotypes under P-deficient conditions. Total SAP was an important root trait under Po conditions. These results might help to breed B. napus with greater P-acquisition ability under low P availability conditions.

Meta-Transcriptomic Analysis Uncovers the Presence of Four Novel Viruses and Multiple Known Virus Genera in a Single Hibiscus rosa-sinensis Plant in Colombia.

Hibiscus is not native to Colombia but well suited to its arid soil and dry climates. A single hibiscus plant from Risaralda, showing black spots on upper and lower sides of its leaves, was collected for virome analysis using meta-transcriptomic high-throughput sequencing technology. Bioinformatic analysis identified 12.5% of the total reads in the Ribo-Zero cDNA library which mapped to viral genomes. BLAST searches revealed the presence of carlavirus, potexvirus, and of known members of the genera Betacarmovirus, Cilevirus, Nepovirus, and Tobamovirus in the sample; confirmed by RT-PCR with virus-specific primers followed by amplicon sequencing. Furthermore, in silico analysis suggested the possibility of a novel soymovirus, and a new hibiscus strain of citrus leprosis virus C2 in the mixed infection. Both RNA dependent RNA polymerase and coat protein gene sequences of the potex and carla viruses shared less than 72% nucleotide and 80% amino acid identities with any alphaflexi- and betaflexi-virus sequences available in GenBank, identifying three novel carlavirus and one potexvirus species in the Hibiscus rosa-sinensis plant. The detection of physalis vein necrosis nepovirus and passion fruit green spot cilevirus in hibiscus are also new reports from Colombia. Overall, the meta-transcriptome analysis identified the complex virome associated with the black spot symptoms on hibiscus leaves and demonstrated the diversity of virus genera tolerated in the mixed infection of a single H. rosa-sinensis plant.

Trehalose-6-phosphate synthase 8 increases photosynthesis and seed yield in Brassica napus.

Trehalose-6-phosphate (T6P) functions as a vital proxy for assessing carbohydrate status in plants. While class II T6P synthases (TPS) do not exhibit TPS activity, they are believed to play pivotal regulatory roles in trehalose metabolism. However, their precise functions in carbon metabolism and crop yield have remained largely unknown. Here, BnaC02.TPS8, a class II TPS gene, is shown to be specifically expressed in mature leaves and the developing pod walls of Brassica napus. Overexpression of BnaC02.TPS8 increased photosynthesis and the accumulation of sugars, starch, and biomass compared to wild type. Metabolomic analysis of BnaC02.TPS8 overexpressing lines and CRISPR/Cas9 mutants indicated that BnaC02.TPS8 enhanced the partitioning of photoassimilate into starch and sucrose, as opposed to glycolytic intermediates and organic acids, which might be associated with TPS activity. Furthermore, the overexpression of BnaC02.TPS8 not only increased seed yield but also enhanced seed oil accumulation and improved the oil fatty acid composition in B. napus under both high nitrogen (N) and low N conditions in the field. These results highlight the role of class II TPS in impacting photosynthesis and seed yield of B. napus, and BnaC02.TPS8 emerges as a promising target for improving B. napus seed yield.

Distinct effector functions mediated by Fc regions of bovine IgG subclasses and their interaction with Fc gamma receptors.

Cattle possess three IgG subclasses. However, the key immune functions, including complement and NK cell activation, and enhancement of phagocytosis, are not fully described for bovine IgG1, 2 and 3. We produced chimeric monoclonal antibodies (mAbs) consisting of a defined variable region linked to the constant regions of bovine IgG1, 2 and 3, and expressed His-tagged soluble recombinant bovine Fc gamma receptors (FcγRs) IA (CD64), IIA (CD32A), III (CD16) and Fcγ2R. Functional assays using bovinized mAbs were developed. IgG1 and IgG3, but not IgG2, activated complement-dependent cytotoxicity. Only IgG1 could activate cattle NK cells to mobilize CD107a after antigen crosslinking, a surrogate assay for antibody-dependent cell cytotoxicity. Both IgG1 and IgG2 could trigger monocyte-derived macrophages to phagocytose fluorescently labelled antigen-expressing target cells. IgG3 induced only weak antibody-dependent cellular phagocytosis (ADCP). By contrast, monocytes only exhibited strong ADCP when triggered by IgG2. IgG1 bound most strongly to recombinant FcγRs IA, IIA and III, with weaker binding by IgG3 and none by IgG2, which bound exclusively to Fcγ2R. Immune complexes containing IgG1, 2 and 3 bound differentially to leukocyte subsets, with IgG2 binding strongly to neutrophils and monocytes and all subclasses binding platelets. Differential expression of the FcγRs on leukocyte subsets was demonstrated by surface staining and/or RT-qPCR of sorted cells, e.g., Fcγ2R mRNA was expressed in monocytes/macrophages, neutrophils, and platelets, potentially explaining their strong interactions with IgG2, and FcγRIII was expressed on NK cells, presumably mediating IgG1-dependent NK cell activation. These data reveal differences in bovine IgG subclass functionality, which do not correspond to those described in humans, mice or pigs, which is relevant to the study of these IgG subclasses in vaccine and therapeutic antibody development.

IgMAT: immunoglobulin sequence multi-species annotation tool for any species including those with incomplete antibody annotation or unusual characteristics.

BACKGROUND: The advent and continual improvement of high-throughput sequencing technologies has made immunoglobulin repertoire sequencing accessible and informative regardless of study species. However, to fully map dynamic changes in polyclonal responses precise framework and complementarity determining region annotation of rearranging genes is pivotal. Most sequence annotation tools are designed primarily for use with human and mouse antibody sequences which use databases with fixed species lists, applying very specific assumptions which select against unique structural characteristics. For this reason, data agnostic tools able to learn from presented data can be very useful with new species or with novel datasets. RESULTS: We have developed IgMAT, which utilises a reduced amino acid alphabet, that incorporates multiple HMM alignments into a single consensus to automatically annotate immunoglobulin sequences from most organisms. Additionally, the software allows the incorporation of user defined databases to better represent the species and/or antibody class of interest. To demonstrate the accuracy and utility of IgMAT, we present analysis of sequences extracted from structural data and immunoglobulin sequence datasets from several different species. CONCLUSIONS: IgMAT is fully open-sourced and freely available on GitHub ( https://github.com/TPI-Immunogenetics/igmat ) for download under GPLv3 license. It can be used as a CLI application or as a python module to be integrated in custom scripts.

First report of Hibiscus soymovirus in Hibiscus rosa-sinensis in Colombia in mixed infection.

Hibiscus is native to southeast Asia but well suited to Colombia's arid soil and dry climates from the coast to the mountains of Bogotá. Viruses infecting hibiscus in Colombia are largely unexplored, with four viruses previously known: hibiscus chlorotic ringspot virus (HCRSV), hibiscus latent Fort Pierce virus (HLFPV), hibiscus latent Singapore virus (HLSV), and citrus leprosis virus C2 (CiLV-C2) (Padmanabhan et al., 2023). Mixed infections between these viruses were frequently detected. A recent virome analysis of a single hibiscus plant from Colombia revealed multiple viruses in mixed infection; : HCRSV, HLFPV, passion fruit green spot virus (PFGSV), a strain of physalis vein necrosis nepovirus, four novel carlavirus, one new potexvirus and a mitovirus. In addition, few smaller contigs of blunervirus and soymovirus were also identified in the high throughput sequencing (HTS) data, but their presence in the mixed infection could not be validated (A. Roy et al. 2023unpublish data). During Brevipalpus-transmitted virus (BTV) surveys, two asymptomatic and 15 hibiscus foliar samples showing green ringspots with central chlorotic spots in senescing areas, mosaic, and black or chlorotic spots were collected from six departments (states) in three geographical regions of Colombia: Tolima (n=4) and Cauca Valley (n=2) (Andean region), Meta (n=6) and Casanare (n=1) (Orinoquia region), and Quindío (n=1) and Risaralda (n=1) (coffee growing region). About 100 mg of 17 hibiscus leaf samples were separately processed for RNA isolation without DNase I treatment and tested for known BTVs, and for newly discovered hibiscus soymovirus (HSV; genus Soymovirus family Caulimoviridae) using PCR assays (Padmanabhan et al. 2023, Wang et al. 2023). To identify potential HSV infection in the samples, published SVF1/SVR1 and newly designed primer pairs (HSV-REP-F/-R and HSV-CPG-F/-R) were used to amplify the 430 nt transactivation (ORF-VI), 631 nt replicase (REP) and 401 nt coat protein gene (CPG), respectively (Supplementary 1). Of 17 samples tested, three from Tolima and one each from Meta and Quindío yielded all three expected size amplicons. Bi-directional sequencing followed by BLASTn analysis revealed 95-98% nt identity with the CPG, REP, and ORF-VI genes of HSV (OP757659). Ribo-depleted libraries were prepared using the RNA extracts of five HSV PCR positive samples. HTS yielded 11.6 to 50.3 million raw reads per sample library. Adapters were trimmed and filtered from the raw reads with Trimmomatic v0.39 and then assembled using SPAdes v3.15.5 (Padmanabhan et al., 2023). Contigs were blasted against the Arabidopsis proteome and a RefSeq-based viral protein database. Potential viral sequences were then blasted against the complete NCBI nr database. Assembled soymo contigs covered 99-100% of the HSV genome, with per-nucleotide read depths of 23.8 to 393. Contigs from the Tolima (Accessions; OR621030- OR621032 and Quindío samples (OR621033) covered 99-100% of the HSV genome and had >96-98% nt identity to Hawaiian isolate (OP757659) whereas the Meta sample contigs covered 78% of the genome with 9495% nt identity. HTS contigs shared >98-99% nt identities with their PCR amplicons. Along with HSV, other virus sequences (HCRSV, HLFPV, PFGSV, CiLV-C2, and mycoviruses) were variously detected from all five libraries. Due to mixed infection no symptom similarity was noticed among these 5 samples. The findings in hibiscus in Tolima, Meta and Quindío represent the first confirmed report of HSV infection in hibiscus in Colombia. The widespread distribution suggests the possibility of HSV dispersion via movement of planting material, and potential further spread to another hibiscus growing region.

British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 3: special circumstances.

The prevalence of cirrhosis has risen significantly over recent decades and is predicted to rise further. Widespread use of non-invasive testing means cirrhosis is increasingly diagnosed at an earlier stage. Despite this, there are significant variations in outcomes in patients with cirrhosis across the UK, and patients in areas with higher levels of deprivation are more likely to die from their liver disease. This three-part best practice guidance aims to address outpatient management of cirrhosis, in order to standardise care and to reduce the risk of progression, decompensation and mortality from liver disease. Part 1 addresses outpatient management of compensated cirrhosis: screening for hepatocellular cancer, varices and osteoporosis, vaccination and lifestyle measures. Part 2 concentrates on outpatient management of decompensated disease including management of ascites, encephalopathy, varices, nutrition as well as liver transplantation and palliative care. In this, the third part of the guidance, we focus on special circumstances encountered in managing people with cirrhosis, namely surgery, pregnancy, travel, managing bleeding risk for invasive procedures and portal vein thrombosis.

British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 1: compensated cirrhosis.

The prevalence of cirrhosis has risen significantly over recent decades and is predicted to rise further. Widespread use of non-invasive testing means cirrhosis is increasingly diagnosed at an earlier stage. Despite this, there are significant variations in outcomes in patients with cirrhosis across the UK, and patients in areas with higher levels of deprivation are more likely to die from their liver disease. This three-part best practice guidance aims to address outpatient management of cirrhosis, in order to standardise care and to reduce the risk of progression, decompensation and mortality from liver disease. Here, in part one, we focus on outpatient management of compensated cirrhosis, encompassing hepatocellular cancer surveillance, screening for varices and osteoporosis, vaccination and lifestyle measures. We also introduce a compensated cirrhosis care bundle for use in the outpatient setting. Part two concentrates on outpatient management of decompensated disease including management of ascites, encephalopathy, varices, nutrition as well as liver transplantation and palliative care. The third part of the guidance covers special circumstances encountered in managing people with cirrhosis: surgery, pregnancy, travel, managing bleeding risk for invasive procedures and portal vein thrombosis.

British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 2: decompensated cirrhosis.

There are two distinct phases in the natural history of cirrhosis: compensated disease (corresponding to Child Pugh A and early Child Pugh B disease), where the patient may be largely asymptomatic, progressing with increasing portal hypertension and liver dysfunction to decompensated disease (corresponding to Child Pugh late B-C), characterised by the development of overt clinical signs, including jaundice, hepatic encephalopathy (HE), ascites, renal dysfunction and variceal bleeding. The transition from compensated cirrhosis to decompensated cirrhosis (DC) heralds a watershed in the nature and prognosis of the disease. DC is a systemic disease, characterised by multiorgan/system dysfunction, including haemodynamic and immune dysfunction. In this second part of our three-part series on the outpatient management of cirrhosis, we address outpatient management of DC, including management of varices, ascites, HE, nutrition, liver transplantation and palliative care. We also introduce an outpatient DC care bundle. For recommendations on screening for osteoporosis, hepatocellular carcinoma surveillance and vaccination see part one of the guidance. Part 3 of the guidance focusses on special circumstances encountered in patients with cirrhosis, including surgery, pregnancy, travel, management of bleeding risk for invasive procedures and portal vein thrombosis.

Outcomes after emergency appendicectomy in patients with liver cirrhosis: a population-based cohort study from England.

INTRODUCTION: The mortality risk after appendicectomy in patients with liver cirrhosis is predicted to be higher than in the general population given the associated risk of perioperative bleeding, infections and liver decompensation. This population-based cohort study aimed to determine the 90-day mortality risk following emergency appendicectomy in patients with cirrhosis. METHODS: Adult patients undergoing emergency appendicectomy in England between January 2001 and December 2018 were identified from two linked primary and secondary electronic healthcare databases, the clinical practice research datalink and hospital episode statistics data. Length of stay, re-admission, case fatality and the odds ratio of 90-day mortality were calculated for patients with and without cirrhosis, adjusting for age, sex and co-morbidity using logistic regression. RESULTS: A total of 40,353 patients underwent appendicectomy and of these 75 (0.19%) had cirrhosis. Patients with cirrhosis were more likely to be older (p < 0.0001) and have comorbidities (p < 0.0001). Proportionally, more patients with cirrhosis underwent an open appendicectomy (76%) compared with 64% of those without cirrhosis (p = 0.03). The 90-day case fatality rate was 6.67% in patients with cirrhosis compared with 0.56% in patients without cirrhosis. Patients with cirrhosis had longer hospital length of stay (4 (IQR 3-9) days versus 3 (IQR 2-4) days and higher readmission rates at 90 days (20% vs 11%, p = 0.019). Most importantly, their odds of death at 90 days were 3 times higher than patients without cirrhosis, adjusted odds ratio 3.75 (95% CI 1.35-10.49). CONCLUSION: Patients with cirrhosis have a threefold increased odds of 90-day mortality after emergency appendicectomy compared to those without cirrhosis.

Co-producing principles to guide health research: an illustrative case study from an eating disorder research clinic.

BACKGROUND: There is significant value in co-produced health research, however power-imbalances within research teams can pose a barrier to people with lived experience of an illness determining the direction of research in that area. This is especially true in eating disorder research, where the inclusion of co-production approaches lags other research areas. Appealing to principles or values can serve to ground collaborative working. Despite this, there has not been any prior attempt to co-produce principles to guide the work of a research group and serve as a basis for developing future projects. METHODS: The aim of this piece of work was to co-produce a set of principles to guide the conduct of research within our lived experience led research clinic, and to offer an illustrative case for the value of this as a novel co-production methodology. A lived experience panel were recruited to our eating disorder research group. Through an iterative series of workshops with the members of our research clinic (composed of a lived experience panel, clinicians, and researchers) we developed a set of principles which we agreed were important in ensuring both the direction of our research, and the way in which we wanted to work together. RESULTS: Six key principles were developed using this process. They were that research should aim to be: 1) real world-offering a clear and concrete benefit to people with eating disorders, 2) tailored-suitable for marginalised groups and people with atypical diagnoses, 3) hopeful-ensuring that hope for recovery was centred in treatment, 4) experiential-privileging the 'voice' of people with eating disorders, 5) broad-encompassing non-standard therapeutic treatments and 6) democratic-co-produced by people with lived experience of eating disorders. CONCLUSIONS: We reflect on some of the positives as well as limitations of the process, highlighting the importance of adequate funding for longer-term co-production approaches to be taken, and issues around ensuring representation of minority groups. We hope that other health research groups will see the value in co-producing principles to guide research in their own fields, and will adapt, develop, and refine this novel methodology.

It important that when researchers are trying to understand illnesses they do this together with people who have experienced them. This can be difficult, because researchers often take over­even if everyone is meant to be working as a team. We are a group of people trying to understand eating disorders and help people who have them get better. In our group there are some people that have experienced an eating disorder, health workers and researchers.We thought it might be helpful if we could start by working out what things were most important to us as a group, and then try to stick by them. We talked a lot together to come up with a list of principles.The six principles we thought were the most important were that research should make a difference to people's lives, see people as individuals, be hopeful, make sure that people have a voice, look at things that aren't traditional therapies, and always work together as equals.There are some issues with what we did; we found it hard to get a good mix of people in our group, and we were lucky in having enough money to pay people to do what we wanted to do, which is not always true. Despite this, we still hope that other teams might look at what we have done, and see if they could build on it, or change it, so it would work for them.

Maternal risk factors for low birthweight and macrosomia: a cross-sectional study in Northern Region, Ghana.

BACKGROUND: Abnormal birthweights are critical public health challenges accountable for most non-communicable diseases and perinatal mortalities. Regardless of the myriad of mixed evidence on maternal factors responsible for abnormal birthweight globally, most of these findings are attained from urban and rural settings. This study serves as one of the key pieces of evidence in view of the increasing prevalence of abnormal birthweight particularly in some parts of semi-rural Ghana. The study, therefore, aims to estimate the prevalence of abnormal birthweight and identify some possible maternal risk factors for abnormal birthweight in Northern Ghana. METHODS: A retrospective cross-sectional study was conducted in Savelugu municipality from February-March 2022. A total of 356 mothers aged 16-46 years, having a neonate and attending postnatal care service, were recruited as study participants. Data were collected from maternal and child health record books and through structured interviews. To identify the maternal risk factors for abnormal birthweight, chi-square/Fischer's exact test and multinomial logistic regression were employed as bivariate and multivariate analyses, respectively, at 95% confidence level. RESULTS: Prevalence rates of low birthweight and macrosomia were 22.2% and 8.7%, respectively. Maternal anaemia in first trimester (AOR 3.226; 95% CI 1.372-7.784) and third trimester (AOR 23.94; 95% CI 7.442-70.01) of gestation was strong predictors for low birthweight. Mothers belonging to minority ethnic groups (AOR 0.104; 95% CI 0.011-0.995); mothers who had ≥ 8 antenatal care visits (AOR 0.249; 95% CI 0.103-0.602); and mothers having neonates whose birth length > 47.5 cm (AOR 0.271; 95% CI 0.113-0.651) had reduced odds for low birthweight. Alternatively, mothers with gestational weeks ≥ 42 (AOR 23.21; 95% CI 4.603-56.19) and mothers from the richest households (highest socioeconomic homes) (AOR 14.25; 95% CI 1.638-23.91) were more likely to birth to macrosomic infants. CONCLUSION: The prevalence rates of low birthweight and macrosomia were relatively high. Anaemia in the first and third trimesters was strong determinants of low birthweight. Being minority ethnic group, frequency of antenatal visits, and childbirth length reduced the risk of low-weight births. Advanced gestational age and socioeconomic status of mothers were also predictors of macrosomia. Hence, nutrition counselling, community health education, and promotion of lifestyle improvement coupled with strengthening of health service delivery are recommended interventions.

Cattle killer immunoglobulin-like receptor expression on leukocyte subsets suggests functional divergence compared to humans.

Cattle, sheep, and goats are the only species outside primates known to have an expanded and diversified family of killer immunoglobulin-like receptors (KIR). Primate KIR are expressed on the surface of NK and T cells and bind MHC-I to control activation. However, the surface expression, ligands and function of bovid KIR remain unknown. Cattle botaKIR2DL1 is the only functional KIR of the same DL-lineage as the expanded KIR in primates and we examined if leukocyte expression patterns were consistent with human. We raised a specific mouse anti-botaKIR2DL1 monoclonal antibody and assessed its utility in flow cytometry, ELISA, and western blot. Unlike primates, cattle DL-lineage KIR (botaKIR2DL1) is present on B cells and monocytes in addition to T cells and low-level expression on NK cells. Expression decreases after in vitro PBMC stimulation with IL-2. This suggests that botaKIR2DL1 has different functions, and potentially ligands, compared to primate KIR.