Service.

There are many dimensions to scientific life. We asked investigators about the impact of service to the scientific community and beyond and how service has shaped their experience, perspective, and research path.

Association between surgeon and hospital volume and outcome of first-time revision hip arthroplasty for aseptic loosening.

Aims: This study evaluates the association between consultant and hospital volume and the risk of re-revision and 90-day mortality following first-time revision of primary hip arthroplasty for aseptic loosening.

Methods: We conducted a cohort study of first-time, single-stage revision hip arthroplasties (RHAs) performed for aseptic loosening and recorded in the National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man between 2003 and 2019. Patient identifiers were used to link records to national mortality data, and to NJR data to identify subsequent re-revision procedures.

Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.

Many mouse models of SARS-CoV-2 infection involve expression of the human ACE2 protein, the entry receptor for SARS-CoV-2 Spike protein, in mouse tissues. However, most of these models suffer from nonphysiological regulation of ACE2 expression, which can lead to atypically severe infections and aberrant sites of viral replication. In this report, we developed and characterized an ACE2 gene replacement (ACE2-GR) mouse strain in which the mouse Ace2 genomic locus was replaced by the entire human ACE2 gene locus, and we investigated the ability of these animals to respond to SARS-CoV-2 infection.

Electropenetrography with Alternating Current Reveals In Situ Changes of Probing Behaviors Associated with Dengue Virus Infection.

Human infection with dengue virus (DENV) results in significant morbidity and mortality around the world. Current methods to investigate virus-associated changes in insect feeding behaviors are largely restricted to video analysis of feeding events outside of the host or intravital microscopy. Electropenetrography, a method originally developed for plant-feeding insects, offers a promising alternative by allowing high-resolution recording of voltage changes across the insect bite interface.

The ATP-exporting channel Pannexin 1 promotes CD8 T cell effector and memory responses.

Sensing of extracellular ATP (eATP) controls CD8 T cell function. Their accumulation can occur through export by specialized molecules, such as the release channel Pannexin 1 (Panx1). Whether Panx1 controls CD8 T cell immune responses , however, has not been previously addressed.

Circulating KLRG1 long-lived effector memory T cells retain the flexibility to become tissue resident.

KLRG1 CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against systemic pathogens. Upon secondary infection, these long-lived effector cells (LLECs) are incapable of forming other circulating KLRG1 memory subsets such as central and effector memory T cells. Thus, KLRG1 memory T cells are frequently referred to as a terminally differentiated population that is relatively short lived.

Cardiovascular Outcomes in Fontan Patients With Right vs Left Univentricular Morphology: A Multicenter Study.

Background: There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.

Objectives: The purpose of this study was to compare the incidence of atrial arrhythmias, thromboembolic events, cardiac transplantation, and death following Fontan palliation in patients with uRV vs uLV.

Methods: The Alliance for Adult Research in Congenital Cardiology conducted a multicenter retrospective cohort study on patients with total cavopulmonary connection Fontan palliation across 12 centers in North America.

Steady-state, therapeutic, and helminth-induced IL-4 compromise protective CD8 T cell bystander activation.

Memory CD8 T cells (T) can be activated into innate-like killers by cytokines like IL-12, IL-15, and/or IL-18; but mechanisms regulating this phenomenon (termed bystander activation) are not fully resolved. We found strain-intrinsic deficiencies in bystander activation using specific pathogen-free mice, whereby basal IL-4 signals antagonize IL-18 sensing. We show that therapeutic and helminth-induced IL-4 impairs protective bystander-mediated responses against pathogens.

Collaboration between IL-7 and IL-15 enables adaptation of tissue-resident and circulating memory CD8 T cells.

Interleukin-7 (IL-7) is considered a critical regulator of memory CD8 T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (T) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that loss had only a modest effect on persistence of circulating memory and T subsets and that IL-7Rα was primarily required for normal basal proliferation.

CD8 T cell tolerance: It doesn't translate.

The mechanisms that make and break CD8 T cell tolerance to self-antigens remain unclear. In this issue of Immunity, Van Der Byl et al. show that tolerant CD8 T cells rapidly adopt an epigenetically and transcriptionally distinct cell state and exhibit impaired protein translation.

Artificial Feeding Systems for Vector-Borne Disease Studies.

This review examines the advancements and methodologies of artificial feeding systems for the study of vector-borne diseases, offering a critical assessment of their development, advantages, and limitations relative to traditional live host models. It underscores the ethical considerations and practical benefits of such systems, including minimizing the use of live animals and enhancing experimental consistency. Various artificial feeding techniques are detailed, including membrane feeding, capillary feeding, and the utilization of engineered biocompatible materials, with their respective applications, efficacy, and the challenges encountered with their use also being outlined.

Erratum: AC-DC Electropenetrography as a Tool to Quantify Probing and Ingestion Behaviors of the Yellow Fever Mosquito () on Mice in Biocontainment.

This corrects the article DOI: 10.30802/AALAS-CM-23-000037. When the above article was first published in the Vol 73 No 6 (December 2023) issue of , figure images were incorrectly associated with the figure legends.

Impact of Fontan Fenestration on Adverse Cardiovascular Outcomes: A Multicentre Study.

Background: Fenestrating a Fontan baffle has been associated with improved perioperative outcomes in patients with univentricular hearts. However, longer-term potential adverse effects remain debated. We sought to assess the impact of a fenestrated Fontan baffle on adverse cardiovascular events including all-cause mortality, cardiac transplantation, atrial arrhythmias, and thromboemboli.

Anxiety and Depression in Adults With Congenital Heart Disease.

Background: A comprehensive understanding of adult congenital heart disease outcomes must include psychological functioning. Our multisite study offered the opportunity to explore depression and anxiety symptoms within a global sample.

Objectives: In this substudy of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults With Congenital Heart Disease-International Study), the authors we investigated the prevalence of elevated depression and anxiety symptoms, explored associated sociodemographic and medical factors, and examined how quality of life (QOL) and health status (HS) differ according to the degree of psychological symptoms.

AC-DC Electropenetrography as a Tool to Quantify Probing and Ingestion Behaviors of the Yellow Fever Mosquito () on Mice in Biocontainment.

A detailed understanding of mosquito probing and ingestion behaviors is crucial in developing novel interventions to interrupt the transmission of important human and veterinary pathogens, but these behaviors are difficult to observe as the mouthparts are inserted into the skin of the host. Electropenetrography (EPG) allows indirect observation, recording, and quantification of probing and ingestion behaviors of arthropods by visualizing the electrical waveform associated with these behaviors. The study of mosquito probing and ingestion behaviors has been limited to the use of human hands as host, which is not suitable for pathogen transmission studies.

An electropenetrography waveform library for the probing and ingestion behaviors of Culex tarsalis on human hands.

Culex tarsalis Coquillett (Diptera: Culicidae) mosquitoes are capable of vectoring numerous pathogens affecting public and animal health. Unfortunately, the probing behaviors of mosquitoes are poorly understood because they occur in opaque tissues. Electropenetrography (EPG) has the potential to elucidate these behaviors by recording the electrical signals generated during probing.

Kruppel-like factor 2+ CD4 T cells avert microbiota-induced intestinal inflammation.

Intestinal colonization by antigenically foreign microbes necessitates expanded peripheral immune tolerance. Here we show commensal microbiota prime expansion of CD4 T cells unified by the Kruppel-like factor 2 (KLF2) transcriptional regulator and an essential role for KLF2+ CD4 cells in averting microbiota-driven intestinal inflammation. CD4 cells with commensal specificity in secondary lymphoid organs and intestinal tissues are enriched for KLF2 expression, and distinct from FOXP3+ regulatory T cells or other differentiation lineages.

Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7.

The sirtuins are NAD -dependent lysine deacylases, comprising seven isoforms (SIRT1-7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity.

Dysfunctional T Follicular Helper Cells Cause Intestinal and Hepatic Inflammation in NASH.

Nonalcoholic steatohepatitis (NASH), characterized by hepatic inflammation and cellular damage, is the most severe form of nonalcoholic fatty liver disease and the fastest-growing indication for a liver transplant. The intestinal immune system is a central modulator of local and systemic inflammation. In particular, Peyer's patches (PPs) contain T follicular helper (Tfh) cells that support germinal center (GC) responses required for the generation of high-affinity intestinal IgA and the maintenance of intestinal homeostasis.

Consultant revision hip arthroplasty volumes and new consultant volume trajectories in England, Wales, Northern Ireland, and the Isle of Man.

Aims: This study describes the variation in the annual volumes of revision hip arthroplasty (RHA) undertaken by consultant surgeons nationally, and the rate of accrual of RHA and corresponding primary hip arthroplasty (PHA) volume for new consultants entering practice.

Methods: National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man were received for 84,816 RHAs and 818,979 PHAs recorded between April 2011 and December 2019. RHA data comprised all revision procedures, including first-time revisions of PHA and any subsequent re-revisions recorded in public and private healthcare organizations.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

Background And Aims: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear.

Methods: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained.