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Effects of mode of assessment, person, and situational variables on the accuracy of self-reports of sexual behavior remain uncertain. To evaluate these influences, 190 young women completed measures of erotophilia and social desirability and then monitored their health-related behaviors with a diary for 8 weeks. They returned on two occasions to complete either a face-to-face interview (FTFI) or a self-administered questionnaire (SAQ) regarding their behavior over the same interval. To check the apparent accuracy of participants' retrospective self-reports, a difference score was calculated by subtracting responses obtained on the FTFI or SAQ from the diary card. Results indicated that both modes of assessment were reliable; reliability did not differ as a function of mode of assessment. However, SAQs elicited less discrepant responses for protected vaginal sex; SAQ and FTFI reports for unprotected sexual behaviors were equivalent. Situational and person variables did not predict accuracy scores, which were impaired at higher frequencies of behavior. Results suggest that both modes of assessment were reliable and SAQs may be more accurate for some sexual behaviors. [ABSTRACT FROM AUTHOR]

The trustworthiness of self-reported sexual behavior data has been questioned since Kinsey's pioneering surveys of sexuality in the United States (Kinsey et al., 1948, 1953). In the era of HIV and AIDS, researchers and practitioners have employed a diversity of assessment techniques but they have not escaped the fundamental problem of measurement error. We review the empirical literature produced since Catania et al.'s (1990) review regarding reliability and validity of self-administered and automated questionnaires, face-to-face interviews, telephone interviews, and self-monitoring approaches. We also provide specific recommendations for improving sexual behavior assessment. It is imperative that standardized self-report instruments be developed and used for sexual risk-behavior assessment. [ABSTRACT FROM AUTHOR]

In 2014, Physostegia chlorotic mottle virus (PhCMoV) was discovered in Austria in Physostegia virginiana . Subsequent collaborative efforts established a link between the virus and severe fruit symptoms on important crops such as tomato, eggplant, and cucumber across nine European countries. Thereafter, specific knowledge gaps, which are crucial to assess the risks PhCMoV can pose for production and how to manage it, needed to be addressed. In this study, the transmission, prevalence, and disease severity of PhCMoV were examined. This investigation led to the identification of PhCMoV presence in a new country, Switzerland. Furthermore, our research indicates that the virus was already present in Europe 30 years ago. Bioassays demonstrated PhCMoV can result in up to 100% tomato yield losses depending on the phenological stage of the plant at the time of infection. PhCMoV was found to naturally infect 12 new host plant species across eight families, extending its host range to 21 plant species across 15 plant families. The study also identified a polyphagous leafhopper (genus Anaceratagallia ) as a natural vector of PhCMoV. Overall, PhCMoV was widespread in small-scale diversified vegetable farms in Belgium where tomato is grown in soil under tunnels, occurring in approximately one-third of such farms. However, outbreaks were sporadic and were associated at least once with the cultivation in tomato tunnels of perennial plants that can serve as a reservoir host for the virus and its vector. To further explore this phenomenon and manage the virus, studying the ecology of the vector would be beneficial., Competing Interests: The author(s) declare no conflict of interest.

Background: Nearly 30% of neuroendocrine tumors (NETs) have evidence of immunohistochemical (IHC) expression of estrogen (ER) and/or progesterone (PR) receptors. Therefore, targeting ER/PR may offer an effective NET-directed treatment to select patients., Methods: We conducted a multicenter Simon two-stage single-arm phase II trial of tamoxifen in patients with metastatic, progressive NETs. Eligible patients had positive IHC expression of ER and/or PR ⩾ 1%. Prior therapy with somatostatin analogs was required for progressing/functioning cases. Main exclusion criterion was aggressive disease requiring cytotoxic therapy. The primary end point was disease control rate (DCR) at week 24 by Response Evaluation Criteria in Solid Tumors version 1.1. We planned to enroll 23 patients in the first stage, to reach a DCR at week 24 of 70% ( versus 50%); if ⩾12 patients reached the primary end point, a total of 37 would be included., Results: From February 2019 to February 2022, 23 out of 59 patients were eligible and enrolled: 15 (65%) were females; the most common sites were pancreas (11; 48%) and small bowel (6; 26%). In all, 13 patients (56.5%) had G2 NETs. At a median follow-up of 27 months, 13 patients (56.5%) had stable disease at week 24 and median progression-free survival (PFS) was 7.9 months [interquartile range (IQR): 3.7-12.1]. The best response was stable disease in 13 patients, with most patients experiencing minor tumor growth. Median PFS times were not significantly different according to ER/PR < or ⩾30% ( p  = 0.49) or ER versus PR expression ( p  = 0.19). One patient experienced grade 2 constipation., Conclusion: Tamoxifen for ER-/PR-positive NETs patients is safe but offers modest antitumor effects., Trial Registry Name: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET)., Url: https://clinicaltrials.gov/ct2/show/NCT03870399?term=03870399&draw=2&rank=1., Registration Number: NCT03870399., Competing Interests: MJB: none; JS: Honoraria from Ipsen and Tersera; TAT: none; LD: none; MDD: honoraria from Novartis and Ipsen; CAM: none; VHFJ: none; TCF: none; RGT: none; RPR: honoraria from Novartis and Ipsen., (© The Author(s), 2023.)

The role of microbiota:immune system dysregulation in the etiology of colorectal cancer (CRC) is poorly understood. CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype, were found at lower frequencies in the colonic tissue of CRC donors compared to healthy controls. Patterns of T cell proliferative responses to a panel of commensal bacteria were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals., (© 2022. Crown.)

Introduction: Familial adenomatous polyposis (FAP) is a condition caused by a constitutional pathogenic variant of the adenomatous polyposis coli gene that results in intestinal adenoma formation and colorectal cancer, necessitating pre-emptive colectomy. We sought to examine interaction between the mucosal immune system and commensal bacteria in FAP to test for immune dysfunction that might accelerate tumorigenesis., Methods: Colonic biopsies were obtained from macroscopically normal mucosal tissue from 14 healthy donors and 13 patients with FAP during endoscopy or from surgical specimens. Intraepithelial and lamina propria lymphocytes were phenotyped. Intraepithelial microbes were labeled with anti-IgA/IgG and analyzed by flow cytometry., Results: Proportions of resident memory CD103-expressing CD8 + and γδ T-cell receptor + intraepithelial lymphocytes were dramatically reduced in both the left and right colon of patients with FAP compared with healthy controls. In lamina propria, T cells expressed less CD103, and CD4 + CD103 + cells expressed less CD73 ectonucleotidase. IgA coating of epithelia-associated bacteria, IgA + peripheral B cells, and CD4 T-cell memory responses to commensal bacteria were increased in FAP., Discussion: Loss of resident memory T cells and γδ T cells in mucosal tissue of patients with FAP accompanies intestinal microbial dysbiosis previously reported in this precancerous state and suggests impaired cellular immunity and tumor surveillance. This may lead to barrier dysfunction, possible loss of regulatory T-cell function, and excess IgA antibody secretion. Our data are the first to implicate mucosal immune dysfunction as a contributing factor in this genetically driven disease and identify potentially critical pathways in the etiology of CRC., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: Strength training is frequently utilized by physical therapists; however, there has been discussion about whether physical therapists utilize strength training adequately. The purpose of this study was to describe and compare the strength training attitudes, behaviors, and knowledge of physical therapists and physical therapy students and to determine how participant characteristics influenced knowledge scores., Methods: An anonymous survey was created in 3 rounds. For round 1, researchers used textbooks to create items assessing demographics, attitudes, behaviors, and knowledge regarding strength training. Rounds 2 and 3 consisted of feedback from 7 content experts until 80% consensus was reached; items were added, removed, or edited based on feedback. The final survey was distributed through social media, list servs, and email targeting physical therapists and students based in the United States. Response frequencies for all items were reported. Overall knowledge scores were calculated by summing correct responses for each item, with a maximum score of 13; scores <70% were considered low. Binomial logistic regression determined which characteristics (demographics, attitudes, or behaviors) influenced whether participants adequately utilized strength training principles (scored ≥70% on knowledge items)., Results: There were 777 physical therapist and 648 student participants. Nearly 90% of therapists and students reported frequently prescribing strength training. Over 48% of therapists felt their professional education did not prepare them to apply strength training (compared with 24% of students), and 68% believed that strength training is inadequately applied in physical therapy (compared with 40% of students). Sixty-two percent of therapists and 55% of students scored ≥70% for knowledge items. Additional strength training education and regular participation in strength training increased the odds of scoring ≥70% on knowledge items., Conclusion: Physical therapists and physical therapy students frequently prescribe strength training despite similarly low knowledge scores. To increase knowledge, greater emphasis on strength training in professional education, continuing education, participation in strength training, or all 3 is warranted., Impact: Strength training is an important intervention used in physical therapy and must be used appropriately to improve the health of patients. According to these findings, strength training education may not currently be optimal, as demonstrated by low knowledge scores by both therapists and students. Further work is needed to determine how knowledge of strength training relates to patient outcomes and also how best to implement strength training in physical therapy education and practice., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo . We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei , by co-culture with syngeneic B. pseudomallei- pulsed dendritic cells. Additionally, we have enriched the DC fraction such that a study of the differential response induced by pulsed DCs of either myeloid or plasmacytoid lineage in syngeneic human T cells was achievable. Whilst both mDCs and pDCs were activated by pulsing, the mDCs contributed the major response to B. pseudomallei with the expression of the migration marker CCR7 and a significantly greater secretion of the proinflammatory TNFα and IL1β. When these DC factions were combined and used to prime syngeneic T cells, a significant proliferation was observed in the CD4 + fraction. Here, we have achieved human T cell priming in vitro with unadjuvanted B. pseudomallei , the causative organism of melioidosis, for which there is currently no approved vaccine. We propose that the approach we have taken could be used to screen for the human cellular response to candidate vaccines and formulations, in order to enhance the cell-mediated immunity required to protect against this intracellular pathogen and potentially more broadly against other, difficult-to-treat intracellular pathogens. To date, the polysaccharide capsule of B. pseudomallei , fused to a standard carrier protein, e.g., Crm, looks a likely vaccine candidate. Dendritic cells (DCs), providing, as they do, the first line of defence to infection, process and present microbial products to the immune system to direct downstream immune responses. Here, we have sought to use DCs ex vivo to identify immunogenic products from heat-killed B. pseudomallei . Using practical volumes of fresh human donor blood, we show that heat-killed B. pseudomallei activated and stimulated the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 from both myeloid and plasmacytoid DCs. Furthermore, B. pseudomallei- pulsed DCs cultured with naïve syngeneic T cells ex vivo , induced the activation and proliferation of the CD4 + T-cell population, which was identified by cell surface marker staining using flow cytometry. Thus, both DC subsets are important for driving primary T helper cell responses to B. pseudomallei in healthy individuals and have the potential to be used to identify immunogenic components of B. pseudomallei for future therapies and vaccines.

During the coronavirus 2019 pandemic we converted our liver transplant waitlist candidate education and support program to a virtual format and expanded it to include ongoing engagement sessions aimed to educate and empower patients to maximize opportunity for live donor liver transplantation. Over a period of 6 months from April 2020 to Sept 2020 we included 21 patients in this pilot quality improvement program. We collected data regarding patient response and potential donor referral activity. Overall, patient response was positive, and some patients saw progress toward live donor liver transplantation by fostering inquiry of potential live liver donors. Optimization of logistical aspects of the program including program flow, technology access, and utilization is required to enhance patient experience. Long-term follow-up is needed to assess impact on the outcome of transplantation rates. Future data collection and analysis should focus on assessment of any potential disparity that may result from utilization of virtual programming. Herein we provide a framework for this type of virtual program and describe our experience., (Copyright © 2021. Published by Elsevier Inc.)

Background: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC)., Results: In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103 + DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD)., Conclusions: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients. Video Abstract.

Background and Aims: The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD]., Methods: Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed., Results: Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses., Conclusions: A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology., (© European Crohn’s and Colitis Organisation 2019.)

Background: Assessing nutritional intake in all-you-care-to-eat dining facilities poses unique challenges. New methods that streamline accurate data collection would facilitate better nutrition intervention research in this dining hall environment, which is common on university campuses., Objective: To compare nutrient and food group intake data of university undergraduate students from a single visit to an all-you-care-to-eat campus dining hall, collected by two methods: multiple-pass dietary recall interview and self-administered, electronic survey., Participants/setting: Undergraduate students (n=42) ages 18 and older were recruited as they exited the dining hall during lunch service hours during 1 week., Design: Using a cross-sectional design, participants completed two dietary assessment methods in random order: an electronic tablet-based exit survey listing the available menu items at that service with drop-down menus to report portion size consumed and a multiple-pass structured dietary interview by a single, trained interviewer., Statistical Analyses Performed: Agreement of nutrients and food groups between the two methods was assessed by Pearson and Spearman correlations and paired t tests. Significance was set at P<0.05., Results: Respondents were primarily underclassmen and women who lived on campus, with 16 of 42 students identifying as white. Students reported an average of 1.1 additional food items via the diet interview method compared with the survey. Average kilocalorie intake by the interview and survey methods was 837±561 and 860±586, respectively. Mean intake of all measured nutrients and all food groups except total and lean protein was not significantly different across the two methods. Spearman correlations between method results ranged across nutrients from r=0.541 to r=0.998 and across food groups from r=0.507 to r=0.948; all were significant at P<0.001. However, mean differences between methods exhibited notable variation., Conclusions: The electronic survey method performs similar to a multiple-pass dietary interview in assessing mean nutrient intake of ethnically diverse university undergraduates in a single eating occasion at an all-you-care-to-eat dining hall, but the survey may not be as efficient at capturing the total number of food items consumed., (Copyright © 2019 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda light chains at time of multiple sclerosis (MS) diagnosis predicts disease progression and whether this was intrinsic to CSF plasmablasts., Methods: CSF and peripheral blood were obtained from patients undergoing elective diagnostic lumbar puncture and included clinically isolated syndrome (CIS) (n=43), relapsing remitting MS (RRMS; n=50), primary progressive MS (PPMS; n=20) and other neurological disease controls, both inflammatory (ONID; n=23) and non-inflammatory (OND; n=114). CSF samples were assayed for free and immunoglobulin-associated light chains and on B cells and plasmablasts. Clinical follow-up data were collected during a 5-year follow-up period where available., Results: There was an increased median CSF κ:λ free light chain (FLC) in all MS groups (CIS: 18.2, 95% CI 6.8 to 30.3; RRMS: 4.4, 95% CI 2.7 to 11.4; PPMS: 12.0, 95% CI 3.6 to 37.1) but not controls (OND: 1.61, 95% CI 1.4 to 1.9; ONID: 1.7, 95% CI 1.3 to 2.2; p<0.001). This ratio predicted Expanded Disability Status Scores (EDSS) progression at 5 years, with a lower median EDSS in the group with high (>10) CSF κ:λ FLC (0.0, 95% CI 0 to 2.5 vs 2.5, 95% CI 0 to 4, high vs low; p=0.049). CSF κ:λ FLC correlated with CSF IgG1 κ:λ (r=0.776; p<0.0001) and was intrinsic to CSF plasmablasts (r=0.65; p=0.026)., Conclusions: These data demonstrate that CSF immunoglobulin κ:λ ratios, determined at the time of diagnostic lumbar puncture, predict MS disease progression and may therefore be useful prognostic markers for early therapeutic stratification., Competing Interests: Competing interests: ARP is an employee of The Binding Site Group Limited who manufacture the CSF FLC assays., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Dendritic cells (DC) determine initiation, type and location of immune responses and, in adults, show decreased Toll-like receptors and some increased cytokine levels on ageing. Few studies in children have characterised DC or explored DC-related mechanisms producing age-related immune changes., Results: The pDC marker BDCA2 (but not CD123) was absent in pre-pubertal children and numbers of pDC decreased with age. Blood and colonic DC were more mature and activated in adults. Decrease in pDC numbers correlated with reduced GM-CSF levels with aging, but increasing IL-4 and IL-8 levels correlated with a more activated DC profile in blood. CXCL16 levels decreased with age., Methods: Blood and colonic DC phenotypes were determined in healthy adults and children by flow cytometry and correlated with aging. Blood DC were divided into plasmacytoid (pDC) and myeloid (mDC) while only mDC were identified in colon. Serum cytokine levels were determined by multiplex cytokine assays and correlated with DC properties., Conclusions: In children, lack of BDCA2, a receptor mediating antigen capture and inhibiting interferon induction, may be immunologically beneficial during immune development. Conversely, reduced pDC numbers, probably secondary to decreasing GM-CSF and increasing cytokine-induced maturation of DC are likely to determine deteriorating immunity with ageing.

Background & Aims: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103 + DC specialize in generating immune tolerance with the functionality of CD11b +/- subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon., Methods: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing., Results: Colonic DC identified were myeloid (mDC, CD11c + CD123 - ) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103 - SIRPα + DC were the major population and with CD103 + SIRPα + DC were CD1c + ILT3 + CCR2 + (although CCR2 was not expressed on all CD103 + SIRPα + DC). CD103 + SIRPα - DC constituted a minor subset that were CD141 + ILT3 - CCR2 - . Proximal colon samples had higher total DC counts and fewer CD103 + SIRPα + cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4 + CD45RA + T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (β7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c + , but not CD141 + mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments., Conclusions: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization.

We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pump deleted E. coli strains. This compound did not interfere with E. coli bacterial growth (MIC > 32 μg/mL) but sensitized this pathogen to hydrophobic antibiotics like macrolides normally inactive on Gram-negative bacteria. In addition, 86 could sensitize E. coli to serum complement killing. These results demonstrate that HldE kinase is a suitable target for drug discovery. They also pave the way toward novel possibilities of treating or preventing bloodstream infections caused by pathogenic Gram negative bacteria by inhibiting specific virulence factors.

Human trials of formaldehyde-inactivated respiratory syncytial virus (FI-RSV) vaccine in 1966-1967 caused disastrous worsening of disease and death in infants during subsequent natural respiratory syncytial virus (RSV) infection. The reasons behind vaccine-induced augmentation are only partially understood, and fear of augmentation continues to hold back vaccine development. We now show that mice vaccinated with FI-RSV show enhanced local recruitment of conventional CD4(+) T cells accompanied by a profound loss of regulatory T cells (Tregs) in the airways. This loss of Tregs was so complete that additional depletion of Tregs (in transgenic depletion of regulatory T-cell mice) produced no additional disease enhancement. Transfer of conventional CD4(+) T cells from FI-RSV-vaccinated mice into naive RSV-infected recipients also caused a reduction in airway Treg responses; boosting Tregs with IL-2 immune complexes failed to restore normal levels of Tregs or to ameliorate disease. However, delivery of chemokine ligands (CCL) 17/22 via the airway selectively recruited airway Tregs and attenuated vaccine-augmented disease, reducing weight loss and inhibiting local recruitment of pathogenic CD4(+) T cells. These findings reveal an unexpected mechanism of vaccine-induced disease augmentation and indicate that selective chemoattraction of Tregs into diseased sites may offer a novel approach to the modulation of tissue-specific inflammation.

In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.

Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. Here we demonstrate that infection of BALB/c mice with respiratory syncytial virus (RSV) induced IL-10 production by CD4(+) and CD8(+) T cells in the airways at later time points (e.g. day 8); a proportion of these cells also co-produced IFN-γ. Furthermore, RSV infection of IL-10(-/-) mice resulted in more severe disease with enhanced weight loss, delayed recovery and greater cell infiltration of the respiratory tract without affecting viral load. In addition, IL-10(-/-) mice had a pronounced airway neutrophilia and heightened levels of pro-inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid. Notably, the proportion of lung T cells producing IFN-γ was enhanced, suggesting that IL-10 may act in an autocrine manner to dampen effector T cell responses. Similar findings were made in mice treated with anti-IL-10R antibody and infected with RSV. Therefore, IL-10 inhibits disease and inflammation in mice infected with RSV, especially during recovery from infection.

A structure-activity relationship study from a screening hit and structure-based design strategy has led to the identification of bisarylureas as potent inhibitors of Streptococcus agalactiae Stk1. As this target has been directly linked to bacterial virulence, these inhibitors can be considered as a promising step towards antivirulence drugs., (Copyright 2010 Elsevier Ltd. All rights reserved.)