Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells.

Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.

A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed alternative lengthening of telomeres (ALT). ALT uses homologous recombination to maintain telomere length and exhibits features of break-induced DNA replication.

Cutaneous Arsenical Exposure Induces Distinct Metabolic Transcriptional Alterations of Kidney Cells.

Arsenicals are deadly chemical warfare agents that primarily cause death through systemic capillary fluid leakage and hypovolemic shock. Arsenical exposure is also known to cause acute kidney injury, a condition that contributes to arsenical-associated death due to the necessity of the kidney in maintaining whole-body fluid homeostasis. Because of the global health risk that arsenicals pose, a nuanced understanding of how arsenical exposure can lead to kidney injury is needed.

Simulation of the COVID-19 handling policy in Indonesia.

Background: This study's background was inspired by the current COVID-19 handling policy, which focuses on the balance of public health and social economy. However, there is a knowledge gap on the dynamic complexity of balancing public health and social economy during the new normal period of COVID-19 handling policy. A system dynamics simulation of the COVID-19 handling policy could be used to understand that gap.

Spatiotemporal immune atlas of the first clinical-grade, gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells.

Functional consequence of myeloid ferritin heavy chain on acute and chronic effects of rhabdomyolysis-induced kidney injury.

Acute kidney injury (AKI) is a serious complication of rhabdomyolysis that significantly impacts survival. Myoglobin released from the damaged muscle accumulates in the kidney, causing heme iron-mediated oxidative stress, tubular cell death, and inflammation. In response to injury, myeloid cells, specifically neutrophils and macrophages, infiltrate the kidneys, and mediate response to injury.

Resident macrophage subpopulations occupy distinct microenvironments in the kidney.

The kidney contains a population of resident macrophages from birth that expands as it grows and forms a contiguous network throughout the tissue. Kidney-resident macrophages (KRMs) are important in homeostasis and the response to acute kidney injury. While the kidney contains many microenvironments, it is unknown whether KRMs are a heterogeneous population differentiated by function and location.

Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19-Associated AKI.

Background: AKI is a common sequela of infection with SARS-CoV-2 and contributes to the severity and mortality from COVID-19. Here, we tested the hypothesis that kidney alterations induced by COVID-19-associated AKI could be detected in cells collected from urine.

Methods: We performed single-cell RNA sequencing (scRNAseq) on cells recovered from the urine of eight hospitalized patients with COVID-19 with (=5) or without AKI (=3) as well as four patients with non-COVID-19 AKI (=4) to assess differences in cellular composition and gene expression during AKI.

First clinical-grade porcine kidney xenotransplant using a human decedent model.

A radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. In preparation for a clinical trial of xenotransplantation, we developed an in vivo pre-clinical human model to test safety and feasibility tenets established in animal models. After performance of a novel, prospective compatible crossmatch, we performed bilateral native nephrectomies in a human brain-dead decedent and subsequently transplanted two kidneys from a pig genetically engineered for human xenotransplantation.

Policy innovation and emergence of innovative health technology: The system dynamics modelling of early COVID-19 handling in Indonesia.

This article examines policy innovation, emergence of innovative health technology and its implication for a health system. The complexity of policy innovation implementation resulting from mixing public health resolution and economic interest will trigger the emergence of innovative health technology, which implies a health system improvement. The findings revealed that: policy innovation based on a science-mix category created the complexity of policy enforcement, affected the scale and speed of COVID-19 transmissions, and triggered the emergence of health innovative technology.

Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance.

Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n = 25), WM (n = 16), and MGUS (n = 18) and in age-matched controls (n = 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls.

[Clinical trial of safety and immunogenicity of new influenza vaccine Grifor in children].

Aim: Assessment of reactogenicity, safety and immunogenicity after single intramuscular immunization of children with Grifor vaccine.

Materials And Methods: Reactogenicity, safety, and immunogenicity of Grifor vaccine compared with Vaxigrip vaccine was evaluated during phase III clinical trial in the Institute of Influenza. Thirty-six children aged 12 - 17 years, divided on 2 groups, participated in single blind comparative prospective randomized trial.

Efficiency of interferon inductor anaferon (pediatric formulation) in prophylaxis of acute respiratory infections in sickly children.

Prophylactic efficiency and safety of anaferon (pediatric formulation) in children aging 1?month to 4 years, including sickly children, was proven. The use of the preparation in children reduced the incidence of acute respiratory infections, alleviated the course of the disease, and decreased the incidence of detection of viral antigens in nasal meatuses.