Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia as a Presentation of a Novel DNMT1 Mutation.

A 50-year-old woman with a 20-year history of gait instability presented with new-onset vertigo and oscillopsia. Examination revealed bilateral vestibular loss, cerebellar ataxia, sensory neuropathy, a "yes-yes" head tremor, nystagmus and a family history of a similar syndrome. Genetic testing for cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (RFC1) was negative, but whole exome sequencing identified a novel mutation in the DNA methyltransferase 1 (DNMT1) gene, broadening the differential diagnosis for this phenotype.

Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons.

Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques ().

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis.

Decoding the hallmarks of allograft dysfunction with a comprehensive pan-organ transcriptomic atlas.

The pathogenesis of allograft (dys)function has been increasingly studied using 'omics'-based technologies, but the focus on individual organs has created knowledge gaps that neither unify nor distinguish pathological mechanisms across allografts. Here we present a comprehensive study of human pan-organ allograft dysfunction, analyzing 150 datasets with more than 12,000 samples across four commonly transplanted solid organs (heart, lung, liver and kidney, n = 1,160, 1,241, 1,216 and 8,853 samples, respectively) that we leveraged to explore transcriptomic differences among allograft dysfunction (delayed graft function, acute rejection and fibrosis), tolerance and stable graft function. We identified genes that correlated robustly with allograft dysfunction across heart, lung, liver and kidney transplantation.

Exploring the Mechanisms of Traditional Chinese Herbal Therapy in Gastric Cancer: A Comprehensive Network Pharmacology Study of the Tiao-Yuan-Tong-Wei decoction.

The use of herbal medicine as an adjuvant therapy in the management of gastric cancer has yielded encouraging outcomes, notably in enhancing overall survival rates and extending periods of disease remission. Additionally, herbal medicines have demonstrated potential anti-metastatic effects in gastric cancer. Despite these promising findings, there remains a significant gap in our understanding regarding the precise pharmacological mechanisms, the identification of specific herbal compounds, and their safety and efficacy profiles in the context of gastric cancer therapy.

Inhibition of MERTK reduces organ fibrosis in mouse models of fibrotic disease.

Transforming growth factor-β (TGFβ) drives fibrosis and disease progression in a number of chronic disorders, but targeting this ubiquitously expressed cytokine may not yield a viable and safe antifibrotic therapy. Here, we sought to identify alternative ways to inhibit TGFβ signaling using human hepatic stellate cells and macrophages from humans and mice in vitro, as well as mouse models of liver, kidney, and lung fibrosis. We identified Mer tyrosine kinase (MERTK) as a TGFβ-inducible effector of fibrosis that was up-regulated during fibrosis in multiple organs in three mouse models.

Intragraft memory-like CD127hiCD4+Foxp3+ Tregs maintain transplant tolerance.

CD4+Foxp3+ regulatory T cells (Tregs) play an essential role in suppressing transplant rejection, but their role within the graft and heterogeneity in tolerance are poorly understood. Here, we compared phenotypic and transcriptomic characteristics of Treg populations within lymphoid organs and grafts in an islet xenotransplant model of tolerance. We showed Tregs were essential for tolerance induction and maintenance.

Human HLA-DR+CD27+ regulatory T cells show enhanced antigen-specific suppressive function.

Regulatory T cells (Tregs) have potential for the treatment of autoimmune diseases and graft rejection. Antigen specificity and functional stability are considered critical for their therapeutic efficacy. In this study, expansion of human Tregs in the presence of porcine PBMCs (xenoantigen-expanded Tregs, Xn-Treg) allowed the selection of a distinct Treg subset, coexpressing the activation/memory surface markers HLA-DR and CD27 with enhanced proportion of FOXP3+Helios+ Tregs.

A metabolic role for CD47 in pancreatic β cell insulin secretion and islet transplant outcomes.

Diabetes is a global public health burden and is characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate insulin secretion and improve insulin sensitivity are in high demand as treatment options. CD47 is a cell surface glycoprotein implicated in multiple cellular functions including recognition of self, angiogenesis, and nitric oxide signaling; however, its role in the regulation of insulin secretion remains unknown.

Surgical Education.

This paper summarizes the proceedings of the joint European Surgical Association ESA/American Surgical Association symposium on Surgical Education that took place in Bordeaux, France, as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on the use of quantitative metrics to understand technical decisions, coaching during training and beyond, and entrustable professional activities were presented by American Surgical Association members and discussed by ESA members in a symposium attended by members of both associations.

Upper gastrointestinal bleeding due to Dieulafoy's lesion of the stomach: a rare case report.

Dieulafoy's lesion is a life-threatening and rare vascular malformation of the submucosal vessel that protrudes to the mucosa of the gastrointestinal tract. The vessel is abnormally dilated, and if it ruptures, it can cause severe acute gastrointestinal bleeding. We report an upper GI bleeding case due to Dieulafoy's lesion in the gastric fundus of the stomach in a 76-year-old female.

Career Needs Assessment for Early Career Academic Surgeons Using a Modified Accelerated Delphi Process.

Introduction: Over the past 2 decades, physicians' wellbeing has become a topic of interest. It is currently unclear what the current needs are of early career academic surgeons (ECAS).

Methods: Consensus statements on academic needs were developed during a Delphi process, including all presenters from the previous European Surgical Association (ESA) meetings (2018-2022).

Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

Background: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content.

Recurrent Pouch Volvulus Following Ileoanal J-Pouch Anastomosis: A Case Report.

For individuals suffering from severe refractory ulcerative colitis (UC) who are unresponsive to medical treatment, a total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery is the gold-standard treatment. However, its complications include anastomotic leaks, pelvic or perianal abscesses, and rare complications such as pouch volvulus. To our knowledge, there is a scarcity of case reports on patients with, specifically, a recurrent pouch volvulus.

The impact of the cytoplasmic ubiquitin ligase TNFAIP3 gene variation on transcription factor NF-κB activation in acute kidney injury.

Nuclear factor κB (NF-κB) activation is a deleterious molecular mechanism that drives acute kidney injury (AKI) and manifests in transplanted kidneys as delayed graft function. The TNFAIP3 gene encodes A20, a cytoplasmic ubiquitin ligase and a master negative regulator of the NF- κB signaling pathway. Common population-specific TNFAIP3 coding variants that reduce A20's enzyme function and increase NF- κB activation have been linked to heightened protective immunity and autoimmune disease, but have not been investigated in AKI.

Intracutaneous Transplantation of Islets Within a Biodegradable Temporizing Matrix as an Alternative Site for Islet Transplantation.

Unlabelled: Intrahepatic islet transplantation for type 1 diabetes is limited by the need for multiple infusions and poor islet viability posttransplantation. The development of alternative transplantation sites is necessary to improve islet survival and facilitate monitoring and retrieval. We tested a clinically proven biodegradable temporizing matrix (BTM), a polyurethane-based scaffold, to generate a well-vascularized intracutaneous "neodermis" within the skin for islet transplantation.