Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor-binding-domain-specific memory B cell and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.

An increase in the prevalence of commensal carrying genes among dairy cattle was observed between 2008 and 2012 in Washington State. To study the molecular epidemiology of this change, we selected 126 -positive and 126-negative isolates for determinations of the multilocus sequence types (MLSTs) and antibiotic resistance phenotypes from obtained during a previous study. For 99 isolates, we also determined the alleles using PCR and sequencing and identified the replicon types of -carrying plasmids. The-negative isolates comprised 76 sequence types (STs) compared with 32 STs in-positive isolates. The-positive isolates formed three MLST clonal complexes, accounting for 83% of these isolates; 52% of-negative isolates clustered into 10 clonal complexes, and the remainder were singletons. Overall,-negative isolates had more diverse genotypes that were distinct to farms, whereas-positive isolates had a clonal population structure and were widely disseminated on farms in both regions included in the study. Plasmid replicon types included IncI1 which predominated, followed by IncFIB and IncFIA/FIB. was the predominant CTX-M gene allele, followed by and There was no significant association between plasmid replicon types and bacterial STs, and neither clonal complexes nor major plasmid groups were associated with two discrete dairy-farming regions of Washington State. Infections caused by extended-spectrum β-lactamase (ESBL)-producing occur globally and present treatment challenges because of their resistance to multiple antimicrobial drugs. Cattle are potential reservoirs of ESBL-producing, and so understanding the causes of successful dissemination of genes in commensal bacteria will inform future approaches for the prevention of antibiotic-resistant pathogen emergence.

The HRI is an effective tool for detecting hepatic steatosis. It provides similar accuracy for different methods of ROI placement (except for random placement) and has good interobserver agreement. It, however, is unable to effectively differentiate between absent and mild steatosis. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:580-586, 2016.

c Enterobacteriaceae-associated bla CTX-M genes have become globally widespread within the past 30 years. Among isolates from Washington State cattle, Escherichia coli strains carrying bla CTX-M (CTX-M E. coli strains) were absent from a set of 2008 isolates but present in a set of isolates from 2011. On 30 Washington State dairy farms sampled in 2012, CTX-M E. coli prevalence was significantly higher on eastern than on northwestern Washington farms, on farms with more than 3,000 adult cows, and on farms that recently received new animals. The addition of fresh bedding to calf hutches at least weekly and use of residual fly sprays were associated with lower prevalence of CTX-M E. coli. In Washington State, the occurrence of human pathogens carrying bla CTX-M genes preceded the emergence of bla CTX-M -associated E. coli in cattle, indicating that these resistance determinants and/or their bacterial hosts may have emerged in human populations prior to their dissemination to cattle populations. E mergence and dissemination of antibiotic resistance traits in Gram-negative bacteria can occur rapidly and across wide geographic distances (1). Bacterial strains carrying the bla CTX-M family of extended-spectrum ␤-lactamase (ESBL) genes have spread globally in less than 30 years (2, 3). Unlike other families of ESBL genes which result from point mutations in preexisting, narrower-spectrum ␤-lactamase genes (bla TEM-1 and bla SHV ) (4), bla CTX-M ␤-lactamase genes originated from chromosomal genes of Kluyvera species (2). The earliest Escherichia coli plasmid-associated bla CTX-M was detected from laboratory dogs used in pharmaceutical research in Japan in 1986, followed by isolations from human patients in Munich, Germany (1989), Argentina (1989), France (1989), and Poland (1996) (2). In North America, bla CTX-Mbearing Escherichia coli strains (CTX-M E. coli strains) were detected in humans in Canada in 2000 (5) and in the United States between 2001 and 2002 (6). By 2007 in the United States, 80% of 15 geographically dispersed medical centers reported E. coli or Klebsiella pneumoniae infections with associated bla CTX-M genes (7). In Washington State, the earliest reported clinical human E. coli strain carrying bla CTX-M was isolated in 2001 in Seattle (6). Currently, CTX-M enzymes are considered the most prevalent ESBLs in isolates of E. coli, K. pneumoniae, and Proteus mirabilis associated with human infections globally (8).In the United States, dairy cattle-associated CTX-M E. coli strains were first reported by Wittum and others in Ohio in 2009 (9). This Ohio research group later reported CTX-M in Salmonella enterica isolates from equine, swine, and turkey sources from six different states (10) and from swine finishing barns in 5 states (11). In the current study, we first tested E. coli isolates from Washington State dairy cattle banked from several earlier research projects to determine the time window of CTX-M E. coli emergence in this region and host species. The results of this retrospective study indicated rece...

No abstract