Antimicrobial resistance in the sexually transmitted bacterium Neisseria gonorrhoeae is compromising the management and control of gonorrhea globally. Optimized use and enhanced stewardship of current antimicrobials and development of novel antimicrobials are imperative. The first in class zoliflodacin (spiropyrimidinetrione, DNA Gyrase B inhibitor) is a promising novel antimicrobial in late-stage clinical development for gonorrhea treatment, i.e., the phase III randomized controlled clinical trial (ClinicalTrials.gov Identifier: NCT03959527) was recently finalized, and zoliflodacin showed non-inferiority compared to the recommended ceftriaxone plus azithromycin dual therapy. Doxycycline, the first-line treatment for chlamydia and empiric treatment for non-gonococcal urethritis, will be frequently given together with zoliflodacin because gonorrhea and chlamydia coinfections are common. In a previous static in vitro study, it was indicated that doxycycline/tetracycline inhibited the gonococcal killing of zoliflodacin in 6-h time-kill curve analysis. In this study, our dynamic in vitro hollow-fiber infection model (HFIM) was used to investigate combination therapies with zoliflodacin and doxycycline. Dose-range experiments using the three gonococcal strains WHO F (susceptible to relevant therapeutic antimicrobials), WHO X (extensively drug-resistant, including ceftriaxone-resistant; zoliflodacin-susceptible), and SE600/18 (zoliflodacin-susceptible strain with GyrB S467N substitution) were conducted simulating combination therapy with a single oral dose of zoliflodacin 0.5-4g combined with a doxycycline daily oral dose of 200mg administered as 100mg twice a day, for 7days (standard dose for chlamydia treatment). Comparing combination therapy of zoliflodacin (0.5-4g single dose) plus doxycycline (200mg divided into 100mg twice a day orally, for 7days) to zoliflodacin monotherapy (0.5-4g single dose) showed that combination therapy was slightly more effective than monotherapy in the killing of N. gonorrhoeae and suppressing emergence of zoliflodacin resistance. Accordingly, WHO F was eradicated by only 0.5g single dose of zoliflodacin in combination with doxycycline, and WHO X and SE600/18 were both eradicated by a 2g single dose of zoliflodacin in combination with doxycycline; no zoliflodacin-resistant populations occurred during the 7-day experiment when using this zoliflodacin dose. When using suboptimal (0.5-1g) zoliflodacin doses together with doxycycline, gonococcal mutants with increased zoliflodacin MICs, due to GyrB D429N and the novel GyrB T472P, emerged, but both the mutants had an impaired biofitness. The present study shows the high efficacy of zoliflodacin plus doxycycline combination therapy using a dynamic HFIM that more accurately and comprehensively simulate gonococcal infection and their treatment, i.e., compared to static in vitro models, such as short-time checkerboard experiments or time-kill curve analysis. Based on our dynamic in vitro HFIM work, zoliflodacin plus doxycycline for the treatment of both gonorrhea and chlamydia can be an effective combination.

Emergency departments (EDs) are the primary source of health care for many patients diagnosed with sexually transmitted infections (STIs). Expedited partner therapy (EPT), treating the partner of patients with STIs, is an evidence-based practice for patients who might not otherwise seek care. Little is known about the use of EPT in the ED. In a national survey, we describe ED medical directors' knowledge, attitudes, and practices of EPT. A cross-sectional survey of medical directors from academic EDs was conducted from July to September 2020 using the Academy of Academic Administrators of Emergency Medicine Benchmarking Group. Primary outcomes were EPT awareness, support, and use. The survey also examined barriers and facilitators. Forty-eight of 70 medical directors (69%) responded. Seventy-three percent were aware of EPT, but fewer knew how to prescribe it (38%), and only 19% of EDs had implemented EPT. Seventy-nine percent supported EPT and were more likely to if they were aware of EPT (89% vs. 54%; P = 0.01). Of nonimplementers, 41% thought EPT was feasible, and 56% thought departmental support would be likely. Emergency department directors were most concerned about legal liability, but a large proportion (44%) viewed preventing sequelae of untreated STIs as "extremely important." Emergency department medical directors expressed strong support for EPT and reasonable levels of feasibility for implementation but low utilization. Our findings highlight the need to identify mechanisms for EPT implementation in EDs.

Idiopathic pulmonary fibrosis (IPF) is a destructive lung disease with a poor prognosis, an unpredictable clinical course, and inadequate therapies. There are currently no measures of disease activity to guide clinicians making treatment decisions. The aim of this study was to develop a PET probe to identify lung fibrogenesis using a pre-clinical model of pulmonary fibrosis, with potential for translation into clinical use to predict disease progression and inform treatment decisions. Eight novel allysine-targeting chelators, PIF-1, PIF-2, …, PIF-8, with different aldehyde-reactive moieties were designed, synthesized, and radiolabeled with gallium-68 or copper-64. PET probe performance was assessed in C57BL/6J male mice 2 weeks after intratracheal bleomycin challenge and in naïve mice by dynamic PET/MR imaging and with biodistribution at 90 min post injection. Lung hydroxyproline and allysine were quantified ex vivo and histological staining for fibrosis and aldehyde was performed. In vivo screening of probes identified 68GaPIF-3 and 68GaPIF-7 as probes with high uptake in injured lung, high uptake in injured lung versus normal lung, and high uptake in injured lung versus adjacent liver and heart tissue. A crossover, intra-animal PET/MR imaging study of 68GaPIF-3 and 68GaPIF-7 confirmed 68GaPIF-7 as the superior probe. Specificity for fibrogenesis was confirmed in a crossover, intra-animal PET/MR imaging study with 68GaPIF-7 and a non-binding control compound, 68GaPIF-Ctrl. Substituting copper-64 for gallium-68 did not affect lung uptake or specificity indicating that either isotope could be used. A series of allysine-reactive PET probes with variations in the aldehyde-reactive moiety were evaluated in a pre-clinical model of lung fibrosis. The hydrazine-bearing probe, 68GaPIF-7, exhibited the highest uptake in fibrogenic lung, low uptake in surrounding liver or heart tissue, and low lung uptake in healthy mice and should be considered for further clinical translation.

A decade ago, massively open online courses (MOOCs) were heralded as the solution to universal, global access to higher education. While they failed to reach this vision, primarily because of teaching-by-telling and learning-by-listening (a PDF of the residential classroom), MOOCs provided the foundational models and infrastructure for emergency remote learning in the pandemic. Reports of remote learning’s death post-pandemic are greatly exaggerated, since the world is now irreversibly hybrid—and will stay that way because many people and organizations value the new opportunities this presents. From now on, when students leave the shelter of classrooms to interact with the world beyond schooling, they must have skills for adept performance both face-to-face and across distance. Colleges, universities, and regions that force all teaching and learning to be face-to-face are dooming their graduates to reduced agency in every other aspect of life. As discussed in recent reports from Harvard, MIT, and Stanford, innovative approaches to digital learning were developed during the pandemic that are now improving campus-based learning. Insights from these approaches offer the opportunity for student engagement at scale, taking advantage of strengths of online instruction such as collapsing time, bridging space, personalizing via rich datastreams, using AI-based instructional assistants and learning partners, delivering content and experience across universities, and sustaining online learning communities after formal instruction ends. Combined, these advances can enable next-generation massive digital hybrid learning, a means to achieve the aspirational vision of universal global access to higher education. A coalition of higher education institutions could begin to realize this vision, an essential step in enabling all learners to survive and thrive in our increasingly turbulent, disruptive global economy and civilization.

Social gatherings are frequent sources of COVID-19 infections, especially among youth. However, little is known about youth testing behaviors before and after gatherings. Our aim was to assess behaviors and perceptions of youth related to testing for COVID-19 before or after social gatherings in order to inform efforts to reduce disease spread. Five open-ended questions were texted to participants aged 14-24 throughout the United States via MyVoice. Using a content analysis approach, two investigators reviewed responses by question, developed a codebook, and independently applied codes. Discrepancies were resolved via discussion. Code frequency and demographic data were summarized using descriptive statistics. Of 1204 participants, 989 responded to at least one question (RR = 94.1%). The mean age was 20.2 years (SD: 2.4 years). Most participants (80.7%) reported testing for COVID-19 at least once. Most (70.6%) were likely to test following an event, especially "[i]f someone at the gathering tested positive," while a smaller number (50.9%) endorsed testing prior to a gathering. Of youth who would not get tested, being vaccinated was the highest reported. Youth in our nationwide sample are likely to test for COVID-19 after an event, though less likely if they are vaccinated. Their desire to test is primarily driven by symptoms, exposures, and requirements. Youth are interested in increased access to home testing. Youth-centered communications regarding testing recommendations and increased test availability for youth may reduce COVID-19 spread among young people and inform future pandemic recommendations.

Science and education represent the world’s best opportunity to tackle global environmental challenges and to make progress toward the Sustainable Development Goals (SDGs), specifically SDG 11 (sustainable cities and communities) and SDG 17 (partnerships for the goals). We address the challenges academic institutions face for effective community engagement through education and extension initiatives and present the Educational Partnerships for Innovation in Communities Network (EPIC-N) framework as a best practice. EPIC-N represents a new paradigm on experiential learning, service learning, and partnership learning that occurs off campus with community organizations and local governments. EPIC-N operates in the US, Africa, and Asia and has started to grow larger in Latin America and the Caribbean since 2022. We argue that the co-production of knowledge methods used by EPIC-N partnerships has potential to target awareness, understanding and action to develop and implement improved strategies at the city and community level to advance SDGs in Latin America. As a disclaimer, we would like to note that all authors of this manuscript are currently, or have previously, been employed by EPIC-N.