Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches.

Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant .

The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant .

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.

Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.

Role of RpoS in Regulating Stationary Phase Salmonella Typhimurium Pathogenesis-Related Stress Responses under Physiological Low Fluid Shear Force Conditions.

The discovery that biomechanical forces regulate microbial virulence was established with the finding that physiological low fluid shear (LFS) forces altered gene expression, stress responses, and virulence of the enteric pathogen Salmonella enterica serovar Typhimurium during the log phase. These log phase LFS-induced phenotypes were independent of the master stress response regulator, RpoS (σ). Given the central importance of RpoS in regulating stationary-phase stress responses of S.

Spaceflight Analogue Culture Enhances the Host-Pathogen Interaction Between and a 3-D Biomimetic Intestinal Co-Culture Model.

Physical forces associated with spaceflight and spaceflight analogue culture regulate a wide range of physiological responses by both bacterial and mammalian cells that can impact infection. However, our mechanistic understanding of how these environments regulate host-pathogen interactions in humans is poorly understood. Using a spaceflight analogue low fluid shear culture system, we investigated the effect of Low Shear Modeled Microgravity (LSMMG) culture on the colonization of Typhimurium in a 3-D biomimetic model of human colonic epithelium containing macrophages.

Longitudinal characterization of multispecies microbial populations recovered from spaceflight potable water.

While sequencing technologies have revolutionized our knowledge of microbial diversity, little is known about the dynamic emergent phenotypes that arise within the context of mixed-species populations, which are not fully predicted using sequencing technologies alone. The International Space Station (ISS) is an isolated, closed human habitat that can be harnessed for cross-sectional and longitudinal functional microbiome studies. Using NASA-archived microbial isolates collected from the ISS potable water system over several years, we profiled five phenotypes: antibiotic resistance, metabolism, hemolysis, and biofilm structure/composition of individual or multispecies communities, which represent characteristics that could negatively impact astronaut health and life-support systems.

Evaluating the effect of spaceflight on the host-pathogen interaction between human intestinal epithelial cells and Salmonella Typhimurium.

Spaceflight uniquely alters the physiology of both human cells and microbial pathogens, stimulating cellular and molecular changes directly relevant to infectious disease. However, the influence of this environment on host-pathogen interactions remains poorly understood. Here we report our results from the STL-IMMUNE study flown aboard Space Shuttle mission STS-131, which investigated multi-omic responses (transcriptomic, proteomic) of human intestinal epithelial cells to infection with Salmonella Typhimurium when both host and pathogen were simultaneously exposed to spaceflight.

Study of the impact of long-duration space missions at the International Space Station on the astronaut microbiome.

Over the course of a mission to the International Space Station (ISS) crew members are exposed to a number of stressors that can potentially alter the composition of their microbiomes and may have a negative impact on astronauts' health. Here we investigated the impact of long-term space exploration on the microbiome of nine astronauts that spent six to twelve months in the ISS. We present evidence showing that the microbial communities of the gastrointestinal tract, skin, nose and tongue change during the space mission.

Evaluation of Acquired Antibiotic Resistance in Exposed to Long-Term Low-Shear Modeled Microgravity and Background Antibiotic Exposure.

The long-term response of microbial communities to the microgravity environment of space is not yet fully understood. Of special interest is the possibility that members of these communities may acquire antibiotic resistance. In this study, cells were grown under low-shear modeled microgravity (LSMMG) conditions for over 1,000 generations (1000G) using chloramphenicol treatment between cycles to prevent contamination.

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age.

Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g.

Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions.

Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered.

Laparoscopic Common Bile Duct Exploration for Choledocholithiasis: Analysis of Practice Patterns of Intermountain HealthCare.

Background: The ideal management of common bile duct (CBD) stones remains controversial, whether with single-stage management using laparoscopic CBD exploration (LCBDE) during laparoscopic cholecystectomy, or with 2-stage management using preoperative or postoperative ERCP. We wished to elucidate the practice patterns within our health system, which includes both large urban referral centers and small rural critical access hospitals.

Study Design: We conducted a retrospective data analysis from our 22-hospital, not-for-profit, integrated healthcare system.

Spaceflight modulates gene expression in the whole blood of astronauts.

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight.

Physiological fluid shear alters the virulence potential of invasive multidrug-resistant non-typhoidal Typhimurium D23580.

serovar Typhimurium strains belonging to sequence type ST313 are a major cause of fatal bacteremia among HIV-infected adults and children in sub-Saharan Africa. Unlike "classical" non-typhoidal (NTS), gastroenteritis is often absent during ST313 infections and isolates are most commonly recovered from blood, rather than from stool. This is consistent with observations in animals, in which ST313 strains displayed lower levels of intestinal colonization and higher recovery from deeper tissues relative to classic NTS isolates.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

Objective: To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals.

Background: Curative-intent surgery for potentially resectable PDAC is underutilized in the United States.

Methods: Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database.

The adaptation of cells grown in simulated microgravity for an extended period is both phenotypic and genomic.

Microorganisms impact spaceflight in a variety of ways. They play a positive role in biological systems, such as waste water treatment but can be problematic through buildups of biofilms that can affect advanced life support. Of special concern is the possibility that during extended missions, the microgravity environment will provide positive selection for undesirable genomic changes.

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study colonization patterns.

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by , we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds.

Incidence of clinical symptoms during long-duration orbital spaceflight.

Background: The environment of spaceflight may elevate an astronaut's clinical risk for specific diseases. The purpose of this study was to derive, as accurately as currently possible, an assessment of in-flight clinical "incidence" data, based on observed clinical symptoms in astronauts on board the International Space Station (ISS).

Methods: Electronic medical records were examined from 46 long-duration ISS crew members, each serving approximately a 6-month mission on board the ISS, constituting 20.

Primary Caregiver Perception of Pain Control following Pediatric Adenotonsillectomy: A Cross-Sectional Survey.

Objectives: To (1) review pain medications prescribed following pediatric adenotonsillectomy (T&A), (2) identify pain medications reported to be helpful, and (3) compare parent-reported outcomes among various combinations of pain medications.

Study Design: Case series with planned data collection.

Setting: Multihospital network.

Variation in costs among surgeons and hospitals in Pediatric tympanostomy tube placement.

Objectives/hypothesis: 1) Identify the major expenses for outpatient pediatric tympanostomy tube placement in a multihospital network. 2) Compare differences for variations in costs among hospitals and surgeons.

Methods: An observational cohort study in a multihospital network using a standardized activity-based accounting system to determine hospital costs for tympanostomy tube placement from February 2011 to January 2015.

Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.

A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens.

Hospital and Surgeon Adherence to Pediatric Tonsillectomy Guidelines Regarding Perioperative Dexamethasone and Antibiotic Administration.

Objectives: To (1) determine adherence to American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines for pediatric tonsillectomy recommending routine administration of perioperative dexamethasone and against routine antibiotic administration among surgeons and hospitals in a multihospital network and (2) evaluate the impact of adherence on the risk of complications.

Study Design: Case series with chart review.

Setting: Multihospital network.

Draft Genome Sequences of Ralstonia pickettii Strains SSH4 and CW2, Isolated from Space Equipment.

Ralstonia pickettii SSH4 and CW2 were isolated from space equipment. Here, we report their draft genome sequences with the aim of gaining insight into their potential to adapt to these environments.