Evaluating responses to temperature during pre-metamorphosis and carry-over effects at post-metamorphosis in the wood tiger moth (Arctia plantaginis)

Insect metamorphosis is one of the most recognized processes delimiting transitions between phenotypes. It has been traditionally postulated as an adaptive process decoupling traits between life stages, allowing evolutionary independence of pre- and post-metamorphic phenotypes. However, the degree of autonomy between these life stages varies depending on the species and has not been studied in detail over multiple traits simultaneously. Here, we reared full-sib larvae of the warningly coloured wood tiger moth (Arctia plantaginis) in different temperatures and examined their responses for phenotypic (melanization change, number of moults), gene expression (RNA-seq and qPCR of candidate genes for melanization and flight performance) and life-histories traits (pupal weight, and larval and pupal ages). In the emerging adults, we examined their phenotypes (melanization and size) and compared them at three condition proxies: heat absorption (ability to engage flight), flight metabolism (ability to sustain flight) and overall flight performance. We found that some larval responses, as evidenced by gene expression and change in melanization, did not have an effect on the adult (i.e. size and wing melanization), whereas other adult traits such as heat absorption, body melanization and flight performance were found to be impacted by rearing temperature. Adults reared at high temperature showed higher resting metabolic rate, lower body melanization, faster heating rate, lower body temperature at take-off and inferior flight performance than cold-reared adults. Thus our results did not unambiguously support the environment-matching hypothesis. Our results illustrate the importance of assessing multiple traits across life stages as these may only be partly decoupled by metamorphosis. This article is part of the theme issue 'The evolution of complete metamorphosis'.Peer reviewe

Label-Free Proteomics Approach Characterizes Plasma Protein Signature of Donor Brain Death

Purpose Despite recent advances in donation after circulatory death, transplants from brain-dead donors remain the sole source in heart transplantation (HTx) worldwide. Due to organ shortage, marginal donors are increasingly used and the utilization of transplants becomes markedly more challenging. They undergo invariably brain death that induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of donor brain death on allografts is not well understood. Methods In a separate prospective, blinded single-center trial, we collected donor plasma samples and relevant clinical patient data from 50 HTx brain-dead donors and as controls plasma samples from age- and gender-matched 23 healthy volunteers. Quantitative label-free proteomics in high definition MSE mode (HDMSE) was carried out on the samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most reliably distinguishing proteins, which classify the donors vs controls. Results With two or more unique proteins per identification, 463 proteins were quantified in our pilot study. A complete separation between donors and controls based on a set of 278 proteins (p-valuePeer reviewe

Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Ischemia-Reperfusion Injury

Purpose Numerous studies have shown that statin therapy initiated early after heart transplantation has beneficial effects on the development of cardiac allograft vasculopathy. Recently, we were able to show in a randomized clinical trial that simvastatin treatment of brain-dead donors conditions the heart transplant to withstand ischemia-reperfusion injury and to reduce the need for rejection treatments early after transplantation. In this study, we analyzed myocardial gene expression profiles in cardiac allografts after donor simvastatin treatment. Methods 84 heart transplant donors received 80 mg of simvastatin via nasogastric tube (n=42), or no treatment (n=42) in a prospective, double-blinded randomized controlled trial. Transmural Tru-Cut biopsies were taken from the apex of left ventricle of the donor heart immediately before reperfusion and 1 hour after reperfusion. 20 heart biopsies from donors without treatment and 20 heart biopsies from donors with simvastatin treatment will be analyzed with RNA sequencing. Results The preliminary analysis of RNA sequencing data from myocardial biopsies revealed altogether 137 significantly differentially expressed genes in all pairwise comparisons. The overall biological functions of these genes were related to gene ontology terms such as response to toxic substance, leukocyte migration, neutrophil mediated immunity, response to lipopolysaccharide, and response to oxidative stress. At the KEGG pathway level, our results indicated alterations in IL-17, TNF, MAPK and the AGE-RAGE signaling pathways. Conclusion We have shown in previous studies that donor simvastatin treatment induces protective effects against IRI in heart transplant recipients. In this study, we were able to detect significantly differentially expressed genes related to effects of simvastatin treatment. In order to single out genes that show beneficial effects of simvastatin treatment, further analysis will be conducted by exploring gene expression changes in specific biological functional categories, such as interleukin signaling and neutrophil degranulation. The complete analysis will be presented at the ISHLT 2019 congress.Peer reviewe

Changes in gene DNA methylation and expression networks accompany caste specialization and age-related physiological changes in a social insect

Social insects provide systems for studying epigenetic regulation of phenotypes, particularly with respect to differentiation of reproductive and worker castes, which typically arise from a common genetic background. The role of gene expression in caste specialization has been extensively studied, but the role of DNA methylation remains controversial. Here, we perform well replicated, integrated analyses of DNA methylation and gene expression in brains of an ant (Formica exsecta) with distinct female castes using traditional approaches (tests of differential methylation) combined with a novel approach (analysis of co-expression and co-methylation networks). We found differences in expression and methylation profiles between workers and queens at different life stages, as well as some overlap between DNA methylation and expression at the functional level. Large portions of the transcriptome and methylome are organized into "modules" of genes, some significantly associated with phenotypic traits of castes and developmental stages. Several gene co-expression modules are preserved in co-methylation networks, consistent with possible regulation of caste-specific gene expression by DNA methylation. Surprisingly, brain co-expression modules were highly preserved when compared with a previous study that examined whole-body co-expression patterns in 16 ant species, suggesting that these modules are evolutionarily conserved and for specific functions in various tissues. Altogether, these results suggest that DNA methylation participates in regulation of caste specialization and age-related physiological changes in social insects.Peer reviewe

Frailty and chronic kidney disease: Current evidence and continuing uncertainties

Frailty, the state of increased vulnerability to physical stressors as a result of progressive and sustained degeneration in multiple physiological systems, is common in those with chronic kidney disease (CKD). In fact, the prevalence of frailty in the older adult population is reported to be 11%, whereas the prevalence of frailty has been reported to be greater than 60% in dialysis-dependent CKD patients. Frailty is independently linked with adverse clinical outcomes in all stages of CKD and has been repeatedly shown to be associated with an increased risk of mortality and hospitalization. In recent years there have been efforts to create an operationalized definition of frailty to aid its diagnosis and to categorize its severity. Two principal concepts are described, namely the Fried Phenotype Model of Physical Frailty and the Cumulative Deficit Model of Frailty. There is no agreement on which frailty assessment approach is superior, therefore, for the time being, emphasis should be placed on any efforts to identify frailty. Recognizing frailty should prompt a holistic assessment of the patient to address risk factors that may exacerbate its progression and to ensure that the patient has appropriate psychological and social support. Adequate nutritional intake is essential and individualized exercise programmes should be offered. The acknowledgement of frailty should prompt discussions that explore the future care wishes of these vulnerable patients. With further study, nephrologists may be able to use frailty assessments to inform discussions with patients about the initiation of renal replacement therapy

Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment

ANCA vasculitis induction management during the COVID-19 pandemic

As the severe acute respiratory syndrome coronavirus 2 pandemic evolved and became a global health threat, the safety of immunosuppression in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) became of utmost important for clinicians and patients. Although timely initiation of immunosuppressive therapy is critical to quell the acute inflammation and prevent AAV-associated mortality and morbidity, concerns for increased susceptibility to Coronavirus Disease 2019 (COVID-19), delayed viral clearance, and decreased humoral response to infection led to speculation about modification in induction therapy practices may be deployed by physicians caring for patients with AAV. This international retrospective cohort study investigated the influence of the COVID-19 pandemic on AAV induction therapy and patient outcomes in different parts of the world by studying differences in treatment regimens in the United States, United Kingdom, and Europe

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 m2 (the therapeutic trial window). Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p<0\ub70001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity