A Multi-omic Analysis of the Human Lung Reveals Distinct Cell Specific Aging and Senescence Molecular Programs.

Age is a major risk factor for lung disease. To understand the mechanisms underlying this association, we characterized the changing cellular, genomic, transcriptional, and epigenetic landscape of lung aging using bulk and single-cell RNAseq (scRNAseq) data. Our analysis revealed age-associated gene networks that reflected hallmarks of aging, including mitochondrial dysfunction, inflammation, and cellular senescence. Cell type deconvolution revealed age-associated changes in the cellular composition of the lung: decreased alveolar epithelial cells and increased fibroblasts and endothelial cells. In the alveolar microenvironment, aging is characterized by decreased AT2B cells and reduced surfactant production, a finding that was validated by scRNAseq and IHC. We showed that a previously reported senescence signature, SenMayo, captures cells expressing canonical senescence markers. SenMayo signature also identified cell-type specific senescence-associated co-expression modules that have distinct molecular functions, including ECM regulation, cell signaling, and damage response pathways. Analysis of somatic mutations showed that burden was highest in lymphocytes and endothelial cells and was associated with high expression of senescence signature. Finally, aging and senescence gene expression modules were associated with differentially methylated regions, with inflammatory markers such as IL1B, IL6R, and TNF being significantly regulated with age. Our findings provide new insights into the mechanisms underlying lung aging and may have implications for the development of interventions to prevent or treat age-related lung diseases.

A single-cell regulatory map of postnatal lung alveologenesis in humans and mice.

Ex-utero regulation of the lungs' responses to breathing air and continued alveolar development shape adult respiratory health. Applying single-cell transposome hypersensitive site sequencing (scTHS-seq) to over 80,000 cells, we assembled the first regulatory atlas of postnatal human and mouse lung alveolar development. We defined regulatory modules and elucidated new mechanistic insights directing alveolar septation, including alveolar type 1 and myofibroblast cell signaling and differentiation, and a unique human matrix fibroblast population. Incorporating GWAS, we mapped lung function causal variants to myofibroblasts and identified a pathogenic regulatory unit linked to lineage marker FGF18, demonstrating the utility of chromatin accessibility data to uncover disease mechanism targets. Our regulatory map and analysis model provide valuable new resources to investigate age-dependent and species-specific control of critical developmental processes. Furthermore, these resources complement existing atlas efforts to advance our understanding of lung health and disease across the human lifespan.

Two new species of burrowing crayfish in the genus Lacunicambarus (Decapoda: Cambaridae) from Alabama and Mississippi.

While sampling for the Rusty Gravedigger, Lacunicambarus miltus, Taylor et al. (2011) found one or more potentially undescribed burrowing crayfish species in the genus Lacunicambarus inhabiting the area between the Pascagoula River and Mobile Bay in southern Alabama and Mississippi. Molecular analyses by Glon et al. (2018) confirmed that samples from this area were genetically distinct from other Lacunicambarus crayfishes. These findings prompted a dedicated sampling trip in January 2020. We used morphological and molecular analyses to investigate the specimens we collected and, based on our results, we describe two new crayfish species: the Lonesome Gravedigger, L. mobilensis sp. nov. and the Banded Mudbug, L. freudensteini sp. nov. Lacunicambarus mobilensis sp. nov. is sister to the Rusty Gravedigger, L. miltus, while L. freudensteini sp. nov. is sister to the Painted Devil Crayfish, L. ludovicianus. Both new species are currently known from a small number of sites in southern Alabama and Mississippi and may require conservation attention. In addition, we provide an updated key to Lacunicambarus crayfishes that includes these new species.

Intraoperative autologous transfusion of hemolyzed blood.

During two cases of lumbar spine surgery with instrumentation, we used intraoperative autologous transfusion (IAT), resulting in hemolysis during collection and hemoglobinuria and coagulation abnormalities after transfusion. Hemolysis during IAT collection can lead to hemoglobinuria and binding of nitric oxide, leading to vasoconstriction. The literature suggests that stroma from damaged cells and contact of the blood with the IAT device can lead to coagulation abnormalities and other morbidities, including adult respiratory distress syndrome.

The US military experience with fresh whole blood during the conflicts in Iraq and Afghanistan.

Since its introduction in the early part of the last century, fresh whole blood (FWB) has been used by the US military as a battlefield expedient resuscitation method, even after the development of component therapy in the 1960s. In the recent conflicts in Iraq and Afghanistan, FWB was used once more, often collected in the setting of a walking blood bank (WBB). Considerable research and opinion from military circles has cited these experiences and sparked renewed interest in FWB as an effective resuscitation tool in the setting of trauma. Despite efforts by the US military to improve the effectiveness and safety of FWB through a series of widely published guidelines, transfusion transmitted infections (TTI) remain a vexing challenge. These experiences in Iraq and Afghanistan will help inform a larger discussion regarding the reintroduction of FWB in civilian trauma resuscitation.

Trauma and thrombelastography: how changes in the understanding of coagulopathy, testing, and hospital systems have changed one group's practice.

Bleeding disorders associated with trauma are of paramount importance when dealing with the acutely injured individual. Statistically, up to 40% of trauma related deaths are assumed to be related to hemorrhage. Historically, there have been many varying positions on the way to handle this entity. Ironically, it is not always the injury but the physiologic sequelae of that injury that lead to trauma associated deaths. Over time, newer theories have been developed to help the clinician begin to understand the etiology and treatment of this process. The purpose of this paper is to review current literature and explain how these new concepts helped change practice in an urban, academic, Level One Trauma Center.