Dexamethasone solution and dexamethasone in Mucolox™ for the treatment of oral inflammatory ulcerative diseases: A phase II randomized clinical trial.

BACKGROUND: Mucolox™ is a mucosal drug delivery system that prolongs the contact time between the oral mucosa and topical corticosteroids, potentially reducing the need for multiple applications daily. This study aimed to assess the clinical efficacy and tolerability of dexamethasone 0.5 mg/5 mL solution in Mucolox™ for the management of oral inflammatory ulcerative diseases. METHODS: Participants were randomly assigned to receive dexamethasone 0.5 mg/5 mL in Mucolox™ (Mucolox™ arm) or dexamethasone 0.5 mg/5 mL solution (standard arm) and instructed to swish/gargle for 5 min three times daily. Changes from pre- to posttreatment patient's sensitivity score (0-10 on a visual analog scale), reticulation/erythema/ulceration score, and oral health-related quality of life were evaluated at baseline and at the end of the study period. RESULTS: Twenty nine patients (75% females) with a median age of 58 years (range 18-79) were enrolled and randomly allocated to the Mucolox™ or standard arm. One subject was excluded. Although statistically significant in both arms, the pre- to posttreatment sensitivity score reduction was higher in the Mucolox™ arm (6.3 vs. 4.4-point reduction). Both arms showed a decrease in the reticulation/erythema/ulceration score between the two visits (7.2 vs. 4.7 [Mucolox™ arm]; 8.0 vs. 4.8 [standard arm]; p > 0.05). Mucolox™ in dexamethasone 0.5 mg/5 mL solution was better tolerated when taste and level of comfort were considered. CONCLUSIONS: Both treatments were effective in the management of oral inflammatory ulcerative diseases. Dexamethasone 0.5 mg/5 mL in Mucolox™ was better tolerated and was slightly better in controlling patients' oral sensitivity. Larger studies are needed to confirm these findings in oral inflammatory ulcerative diseases patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04540133.

Human Papillomavirus (HPV) Education and Knowledge Among Medical and Dental Trainees.

Persistent human papillomavirus (HPV) infection is responsible for the majority of oropharyngeal and cervical cancers in the USA. Currently, HPV curricula within medical and dental schools are not standardized. As such, we implemented a brief online educational intervention to increase medical and dental trainees' knowledge of the HPV vaccine and the association between HPV and cancer. The objectives of this study were to (1) assess medical and dental trainees' baseline knowledge regarding HPV and HPV vaccine, (2) determine the willingness to recommend the HPV vaccine to patients, and (3) evaluate the impact of an online intervention on HPV-related knowledge. Medical and dental trainees from two large academic centers in the USA were asked to fill out an online pre-intervention questionnaire, followed by a 10-min HPV educational intervention based on the Center of Disease Control and Prevention (CDC) resources, and then a post-intervention questionnaire. There were 75 participants (67.4% females; median age 18-30 years). When asked about HPV-related cancer types, the correct response increased from 28.4% (pre-intervention) to 51.9% (post-intervention; p < 0.01). When asked about the prevalence of HPV infections, the correct response improved from 36 to 72% (p < 0.01). There was also a 25.2% improvement in identifying the correct HPV vaccination dosing schedule (p < 0.01). Eighty-seven percent of the participants mentioned that the online education improved their HPV knowledge, and 68.5% reported that they were more likely to recommend HPV vaccine after the online intervention. The proposed online educational intervention was effective at improving HPV-related cancer and HPV vaccine knowledge as well as attitudes towards vaccine recommendation among dental and medical trainees and could be implemented in medical and dental school curricula in the future.

Pathogens manipulate host autophagy through injected effector proteins.

Macroautophagy/autophagy plays a dual role in many physiological processes of multicellular eukaryotes. In plants, autophagy can be used by both host and pathogen for a beneficiary infection outcome. Plants employ a two-tier innate immune system to defend against invading pathogens. Cell surface localized pattern recognition receptors recognize conserved pathogen-associated molecular patterns (PAMPs) and launch pattern-triggered immunity (PTI) to provide broad-spectrum resistance. Pathogens inject a battery of effector proteins into their hosts to counter PTI and compromise the primary immune response. Hosts induce a second layer of defense called effector-triggered immunity (ETI) to counter the effects of these effectors. In addition to ETI and PTI, autophagy is emerging as a central cellular process modulated by both host and pathogens toward their respective advantage. Pathogens lacking the ability to inject effectors are compromised in virulence. However, molecular targets and biochemical characterization of most of these effector proteins remain elusive. In a recent paper we presented a systematic analysis of interaction between autophagy proteins of Arabidopsis thaliana with effectors from bacterial, fungal, oomycete and nematode pathogens. Abbreviations: ATG, autophagy related; BiFC, bimolecular fluorescence complementation; ETI, effector-triggered immunity; PAMPs, pathogen-associated molecular patterns; PTI, pattern-triggered immunity.

Phytopathogen Effectors Use Multiple Mechanisms to Manipulate Plant Autophagy.

Autophagy is a central part of immunity and hence is a key target of pathogens. However, the precise molecular mechanisms by which plant pathogens manipulate autophagy remain elusive. We identify a network of 88 interactions between 184 effectors from bacterial, fungal, oomycete, and nematode pathogens with 25 Arabidopsis autophagy (ATG) proteins. Notably, Pseudomonas syringae pv tomato (Pto) bacterial effectors HrpZ1, HopF3, and AvrPtoB employ distinct molecular strategies to modulate autophagy. Calcium-dependent HrpZ1 oligomerization targets ATG4b-mediated cleavage of ATG8 to enhance autophagy, while HopF3 also targets ATG8 but suppresses autophagy, with both effectors promoting infection. AvrPtoB affects ATG1 kinase phosphorylation and enhances bacterial virulence. Since pathogens inject limited numbers of effectors into hosts, our findings establish autophagy as a key target during infection. Additionally, as autophagy is enhanced and inhibited by these effectors, autophagy likely has different functions throughout infection and, thus, must be temporally and precisely regulated for successful infection.