The Anomalous Mei-yu Rainfall of Summer 2020 from a Circulation Clustering Perspective: Current and Possible Future Prevalence.

Highly unusual amounts of rainfall were seen in the 2020 summer in many parts of China, Japan, and South Korea. At the intercontinental scale, case studies have attributed this exceptional event to a displacement of the climatological western North Pacific subtropical anticyclone, potentially associated Indian Ocean sea surface temperature patterns and a mid-latitude wave train emanating from the North Atlantic. Using clusters of spatial patterns of sea level pressure, we show that an unprecedented 80% of the 2020 summer days in East Asia were dominated by clusters of surface pressure greater than normal over the South China Sea. By examining the rainfall and water vapor fluxes in other years when these clusters were also prevalent, we find that the frequency of these types of clusters was likely to have been largely responsible for the unusual rainfall of 2020. From two ensembles of future climate projections, we show that summers like 2020 in East Asia may become more frequent and considerably wetter in a warmer world with an enhanced moisture supply.

Improved resolution of bacteria by high throughput sequence analysis of the rRNA internal transcribed spacer.

Current high throughput sequencing (HTS) methods are limited in their ability to resolve bacteria at or below the genus level. While the impact of this limitation may be relatively minor in whole-community analyses, it constrains the use of HTS as a tool for identifying and examining individual bacteria of interest. The limited resolution is a consequence of both short read lengths and insufficient sequence variation within the commonly targeted variable regions of the small-subunit rRNA (SSU) gene. The goal of this work was to improve the resolving power of bacterial HTS. We developed an assay targeting the hypervariable rRNA internal transcribed spacer (ITS) region residing between the SSU and large-subunit (LSU) rRNA genes. Comparisons of the ITS region and two SSU regions using annotated bacterial genomes in GenBank showed much greater resolving power is possible with the ITS region. This report presents a new HTS method for analyzing bacterial composition with improved capabilities. The greater resolving power enabled by the ITS region arises from its high sequence variation across a wide range of bacterial taxa and an associated decrease in taxonomic heterogeneity within its OTUs. Although the method should be adaptable to any HTS platform, this report presents PCR primers, amplification parameters, and protocols for Illumina-based analyses.

T-cell production of matrix metalloproteinases and inhibition of parasite clearance by TIMP-1 during chronic Toxoplasma infection in the brain.

Chronic infection with the intracellular protozoan parasite Toxoplasma gondii leads to tissue remodelling in the brain and a continuous requirement for peripheral leucocyte migration within the CNS (central nervous system). In the present study, we investigate the role of MMPs (matrix metalloproteinases) and their inhibitors in T-cell migration into the infected brain. Increased expression of two key molecules, MMP-8 and MMP-10, along with their inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), was observed in the CNS following infection. Analysis of infiltrating lymphocytes demonstrated MMP-8 and -10 production by CD4+ and CD8+ T-cells. In addition, infiltrating T-cells and CNS resident astrocytes increased their expression of TIMP-1 following infection. TIMP-1-deficient mice had a decrease in perivascular accumulation of lymphocyte populations, yet an increase in the proportion of CD4+ T-cells that had trafficked into the CNS. This was accompanied by a reduction in parasite burden in the brain. Taken together, these findings demonstrate a role for MMPs and TIMP-1 in the trafficking of lymphocytes into the CNS during chronic infection in the brain.

CCR7-dependent immunity during acute Toxoplasma gondii infection.

The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells and T cells. Interactions with its ligands, CCL19 and CCL21, facilitate priming of immune responses in lymphoid tissue, yet CCR7-independent immune responses can be generated in the presence of sufficient antigen. In these studies, we investigated the role of CCR7 signaling in the generation of protective immune responses to the intracellular protozoan parasite Toxoplasma gondii. The results demonstrated a significant increase in the expression of CCL19, CCL21, and CCR7 in peripheral and central nervous system (CNS) tissues over the course of infection. Unexpectedly, despite the presence of abundant antigen, CCR7 was an absolute requirement for protective immunity to T. gondii, as CCR7(-/-) mice succumbed to the parasite early in the acute phase of infection. Although serum levels of interleukin 12 (IL-12), IL-6, tumor necrosis factor alpha (TNF-alpha), and IL-10 remained unchanged, there was a significant decrease in CCL2/monocyte chemoattractant protein 1 (MCP-1) and inflammatory monocyte recruitment to the site of infection. In addition, CCR7(-/-) mice failed to produce sufficient gamma interferon (IFN-gamma), a critical Th1-associated effector cytokine required to control parasite replication. As a result, there was increased parasite dissemination and a significant increase in parasite burden in the lungs, livers, and brains of infected mice. Adoptive-transfer experiments revealed that expression of CCR7 on the T-cell compartment alone is sufficient to enable T-cell priming, increase IFN-gamma production, and allow the survival of CCR7(-/-) mice. These data demonstrate an absolute requirement for T-cell expression of CCR7 for the generation of protective immune responses to Toxoplasma infection.

Bacterial particle endocytosis by epithelial cells is selective and enhanced by tumor necrosis factor receptor ligands.

Bacterial pathogens use virulence strategies to invade epithelial barriers, but active processes of epithelial cells may also contribute to the endocytosis of microbial particles. To focus on the latter, we studied the uptake of fixed and fluorescently labeled bacterial particles in intestinal and bronchoepithelial cell cultures and found it to be enhanced in Caco-2BBe and NCI-H292 cells after treatment with tumor necrosis factor alpha and an agonist antibody against the lymphotoxin beta receptor. Confocal fluorescence microscopy, flow cytometry, and transmission electron microscopy revealed that Staphylococcus aureus and Yersinia enterocolitica were readily endocytosed, although there was scant uptake of Shigella sonnei, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae particles. Endocytosed Staphylococcus was often associated with cytoplasmic claudin-4 vesicles; this was not found for Yersinia, suggesting that cytokine treatment upregulated two distinct endocytosis pathways. Interestingly, when Staphylococcus and Yersinia were coincubated with epithelial monolayers, the cells were unlikely to take up Yersinia unless they had also endocytosed large numbers of Staphylococcus particles, although the two bacteria were apparently processed in distinct compartments. Cytokine treatment induced an upregulation and redistribution of beta1 integrin to the apical surface of NCI-H292 cells; consistent with this effect, treatment with anti-beta1 integrin antibody blocked uptake of both Yersinia and Staphylococcus in NCI-H292 and Caco-2BBe cells. Our results suggest that capture of bacterial particles by mucosal epithelial cells is selective and that different endocytic mechanisms are enhanced by proinflammatory cytokines.

Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality.

OBJECTIVE: The purpose of this study was to examine the outcome implications of implementing a severe sepsis bundle in an emergency department as a quality indicator set with feedback to modify physician behavior related to the early management of severe sepsis and septic shock. DESIGN: Two-year prospective observational cohort. SETTING: Academic tertiary care facility. PATIENTS: Patients were 330 patients presenting to the emergency department who met criteria for severe sepsis or septic shock. INTERVENTIONS: Five quality indicators comprised the bundle for severe sepsis management in the emergency department: a) initiate central venous pressure (CVP)/central venous oxygen saturation (Scvo2) monitoring within 2 hrs; b) give broad-spectrum antibiotics within 4 hrs; c) complete early goal-directed therapy at 6 hrs; d) give corticosteroid if the patient is on vasopressor or if adrenal insufficiency is suspected; and e) monitor for lactate clearance. MEASUREMENTS AND MAIN RESULTS: Patients had a mean age of 63.8 +/- 18.5 yrs, Acute Physiology and Chronic Health Evaluation II score 29.6 +/- 10.6, emergency department length of stay 8.5 +/- 4.4 hrs, hospital length of stay 11.3 +/- 12.9 days, and in-hospital mortality 35.2%. Bundle compliance increased from zero to 51.2% at the end of the study period. During the emergency department stay, patients with the bundle completed received more CVP/Scvo2 monitoring (100.0 vs. 64.8%, p < .01), more antibiotics (100.0 vs. 89.7%, p = .04), and more corticosteroid (29.9 vs. 16.2%, p = .01) compared with patients with the bundle not completed. In a multivariate regression analysis including the five quality indicators, completion of early goal-directed therapy was significantly associated with decreased mortality (odds ratio, 0.36; 95% confidence interval, 0.17-0.79; p = .01). In-hospital mortality was less in patients with the bundle completed compared with patients with the bundle not completed (20.8 vs. 39.5%, p < .01). CONCLUSIONS: Implementation of a severe sepsis bundle using a quality improvement feedback to modify physician behavior in the emergency department setting was feasible and was associated with decreased in-hospital mortality.

The removal of coins from the upper esophageal tract of children by emergency physicians: a pilot study.

OBJECTIVE: There are few reports in the medical literature describing removal of a coin from the upper esophageal tract of a child by an emergency physician. However, given the nature of their training and practice, emergency physicians are well suited to perform this common procedure. We describe our experience with this procedure. METHODS: This was a retrospective review of a continuous quality improvement data set from a university-based tertiary care pediatric emergency department between Nov. 1, 2003, and Mar. 31, 2004. RESULTS: Thirteen children, with a median age of 20 months, underwent rapid sequence intubation and had coins successfully removed from their upper esophageal tract by emergency physicians. In 10 cases, the coin was visible at laryngoscopy and removed with Magill forceps. In 3 cases this approach failed and a Foley catheter was used to remove the coin. One child suffered a tonsillar abrasion and two sustained minor lip trauma, but all were extubated and discharged home from the emergency department with no significant complications. Eleven of the 13 patients were successfully followed up, and the parents reported no problems. CONCLUSIONS: This pilot study suggests that the removal of a coin from the upper esophageal tract by an emergency physician can be both safe and effective. A larger study is needed before this procedure can be generally recommended.