The molecular initiators of infection-associated pain are not understood. We recently found that uropathogenic E. coli (UPEC) elicited acute pelvic pain in murine urinary tract infection (UTI). UTI pain was due to E. coli lipopolysaccharide (LPS) and its receptor, TLR4, but pain was not correlated with inflammation. LPS is known to drive inflammation by interactions between the acylated lipid A component and TLR4, but the function of the O-antigen polysaccharide in host responses is unknown. Here, we examined the role of O-antigen in pain using cutaneous hypersensitivity (allodynia) to quantify pelvic pain behavior and using sacral spinal cord excitability to quantify central nervous system manifestations in murine UTI. A UPEC mutant defective for O-antigen biosynthesis induced chronic allodynia that persisted long after clearance of transient infections, but wild type UPEC evoked only acute pain. E. coli strains lacking O-antigen gene clusters had a chronic pain phenotype, and expressing cloned O-antigen gene clusters altered the pain phenotype in a predictable manner. Chronic allodynia was abrogated in TLR4-deficient mice, but inflammatory responses in wild type mice were similar among E. coli strains spanning a wide range of pain phenotypes, suggesting that O-antigen modulates pain independent of inflammation. Spinal cords of mice with chronic allodynia exhibited increased spontaneous firing and compromised short-term depression, consistent with centralized pain. Taken together, these findings suggest that O-antigen functions as a rheostat to modulate LPS-associated pain. These observations have implications for an infectious etiology of chronic pain and evolutionary modification of pathogens to alter host behaviors.

ence of both serotype-specific determinants (3,16,19,20,39,43,60) and cross-reactive determinants (1,3,5,12,13,26,43). The immunological relationships among morphotype E flagellins have been analyzed by using monoclonal antibodies (43,60). In addition to serotype-specific and broadly cross-reactive epitopes, other epitopes were common among subgroups of closely related flagellin serotypes within morphotype E. Immunogold labeling studies demonstrated that serotype-specific determinants tend to be surface exposed in intact flagellar filaments, while cross-reactive determinants tend to be hidden (43,60).DNA sequence analysis of flagellin structural genes from E. coli K-12 (24), Serratia marcescens (10), and several Salmonella serovars (15,48,58,59) demonstrated that the termini of flagellin proteins are conserved. The central region of the flagellin molecule is variable and gives rise to serotype-specific epitopes (6,16,18,19,23,36,45,47,48,58). The flagellin protein therefore possesses several distinct structural domains (34,46,(51)(52)(53)(54)56). These have been mapped on the primary structure of the flagellin molecule and localized within the intact flagellar filament by electron density mapping studies (57). The conserved, terminal regions of flagellin were found to be associated with the inner structure of intact flagellar filaments. The outer surfaceexposed architecture is formed from the folding outward of 5395

Appendiceal carcinomas follow a more protracted clinical course than carcinoids, which usually present as acute appendicitis. Caution is needed when diagnosing simple appendicitis in older patients with longer symptom duration, particularly if a mass is present. Patients with appendiceal carcinoma should be offered completion right-hemicolectomy. Carcinoma has a poor prognosis.

Protein K, a recently described outer membrane protein correlated with encapsulation in Escherichia coli (Paakkanen et al., J. Bacteriol. 139:835-841, 1979), has been purified to apparent homogeneity. Purification was based upon the noncovalent association of protein K with peptidoglycan, and the purified protein was shown to form sodium dodecyl sulfate-resistant oligomers on polyacrylamide gels. Incorporation of small amounts (10-10 to 10-l M) of purified protein K into artificial lipid bilayers resulted in an increase, by many orders of magnitude, in membrane conductance. The increased conductance resulted from the formation of large, water-filled, ion-permeable channels exhibiting singlechannel conductance in 1.0 M KCl of 1.83 nS. The membrane conductance showed a linear relationship between current and applied voltage and was not voltage induced or regulated. The channel was permeable to large organic ions (e.g., Tris+ Cl-) and, based upon a pore length of 7.5 nm, a minimum channel diameter of 1.2 nm was estimated; these properties resemble values for other enteric porins. The possible biological role of the pores produced by protein K is discussed.

It has been over a year since the first known case of coronavirus disease emerged, yet the pandemic is far from over. To date, the coronavirus pandemic has infected over eighty million people and has killed more than 1.78 million worldwide. This study aims to explore "how useful is Reddit social media platform to surveil COVID-19 pandemic?" and "how do people' s concerns/behaviors change over the course of COVID-19 pandemic in North Carolina?". The purpose of this study was to compare people's thoughts, behavior changes, discussion topics, and the number of confirmed cases and deaths by applying natural language processing (NLP) to COVID-19 related data.Methods: In this study, we collected COVID-19 related data from 18 subreddits of North Carolina from March to August 2020. Next, we applied methods from natural language processing and machine learning to analyze collected Reddit posts using feature engineering, topic modeling, custom named-entity recognition (NER), and BERT-based (Bidirectional Encoder Representations from Transformers) sentence clustering. Using these methods, we were able to glean people's responses and their concerns about COVID-19 pandemic in North Carolina. Results:We observed a positive change in attitudes towards masks for residents in North Carolina. The highfrequency words in all subreddit corpora for each of the COVID-19 mitigation strategy categories are: Distancing (DIST)-"social distance/distancing", "lockdown", and "work from home"; Disinfection (DIT)-"(hand) sanitizer/soap", "hygiene", and "wipe"; Personal Protective Equipment (PPE)-"mask/facemask(s)/face shield", "n95(s)/kn95", and "cloth/ gown"; Symptoms (SYM)-"death", "flu/influenza", and "cough/coughed"; Testing (TEST)-"cases", "(antibody) test", and "test results (positive/negative)". Conclusion:The findings in our study show that the use of Reddit data to monitor COVID-19 pandemic in North Carolina (NC) was effective. The study shows the utility of NLP methods (e.g. cosine similarity, Latent Dirichlet Allocation (LDA) topic modeling, custom NER and BERT-based sentence clustering) in discovering the change of the public's concerns/behaviors over the course of COVID-19 pandemic in NC using Reddit data. Moreover, the results show that social media data can be utilized to surveil the epidemic situation in a specific community.