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ABSTRACT IMPACT: This project seeks to identify unique host responses that are biomarkers for specific urethral pathogens, and which can be used in the development of point-of-care (POC) STI diagnostics. OBJECTIVES/GOALS: How Chlamydia trachomatis (CT) and other common STIs, e.g. Neisseria gonorrhoeae, evade immunity and elicit pathology in the male urethra is poorly understood. Our objective is to determine how STI-infected urethral epithelial cells, as well as the uninfected ‘bystander’ cells with which infected cells communicate, respond to CT and other STIs. METHODS/STUDY POPULATION: We evaluated how immortalized urethral cell lines - including transduced human urethral epithelial cells (THUECs) - respond to increasing doses of CT infectious particles using in vitro one-step progeny assays performed in the presence or absence of cycloheximide, a drug that inhibits eukaryotic protein synthesis. We will perform concurrent single-cell RNA sequencing (scRNA-seq) and multiplex cytokine analyses to determine how different CT doses impact the transcriptomes of infected and bystander urethral epithelial cells and modulate cytokine production of the overall monolayer. Results of these experiments will inform the feasibility of performing similar analyses in situ using urethral swabs from men with clinically diagnosed urethritis. RESULTS/ANTICIPATED RESULTS: Our results demonstrate that immune-competent urethral cell monolayers strongly resist CT infection, unless most of the cells are simultaneously infected. This suggests that uninfected bystander cells sense CT-infected cells and secrete soluble factors that may act to limit CT proliferation in infected cells and to inform remaining uninfected cells that a potential pathogen is present. We anticipate that our scRNA-seq and cytokine analyses will identify both specific effector pathways that protect against CT and intracellular signals that modulate them. We speculate that these pathways and signals may differ during infection with CT and other STIs. Importantly, we anticipate that our in vitro model of CT infection will be highly representative of in situ immune responses observed in urethras of infected men. DISCUSSION/SIGNIFICANCE OF FINDINGS: In men, common STIs including CT are usually managed syndromically due to a lack of POC diagnostics. By determining how STIs elicit urethral inflammation and identifying countermeasures that STIs use to evade urethral immunity, we can identify host responses that serve as biomarkers for urethritis, generally, and for specific urethral pathogens.
Cognitive and behavioral impairment are common in children living with perinatally acquired HIV (pHIV) and children exposed to HIV in utero but uninfected (HEU).
We sought to determine the prevalence of adverse behavioral symptomatology using a Thai-translated and validated version of the SNAP-IV questionnaire and assess cognitive function utilizing the Children's Color Trails Test, Delis-Kaplan Executive Function System, and the Wechsler Intelligence Scales, in our cohort of Thai adolescents (10–20 years old) with well-controlled pHIV compared to HEU and HIV-unexposed, uninfected youth. We then evaluated the interaction between HIV status, behavioral impairment, and executive function outcomes independent of demographic variables.
After controlling for demographic factors of age and household income, adolescents with pHIV had higher inattentive symptomatology and poorer neuropsychological test scores compared to uninfected controls. Significant interactions were found between inattention and executive function across multiple neurocognitive tests.
Behavioral impairment and poor executive functioning are present in adolescents with well-controlled pHIV compared to HIV-uninfected matched peers. The SNAP-IV questionnaire may be a useful tool to identify those with attentional impairment who may benefit from further cognitive testing in resource-limited settings.
Carbapenem-resistant Enterobacteriaceae (CRE) are an important cause of healthcare-associated infections (HAIs) in human hospitals. The Philadelphia Department of Public Health (PDPH) made CRE reportable in April 2018. In May 2019, the Matthew J. Ryan Veterinary Hospital (MJRVH) reported an NDM-5 Escherichia coli cluster in companion animals to the PDPH. In total, 15 infected animals (14 dogs and 1 cat) were reported between July 2018 and June 2019, with no new infections after June 2019. Limited literature is available on the prevalence of CRE in companion animals, and recommendations for dealing with CRE infections currently target human healthcare settings. Methods: A collaborative containment response included assessing interspecies transmission to veterinary staff and a comprehensive evaluation of the infection control program at MJRVH. MJRVH notified all owners of affected animals verbally and via notification letters with PDPH recommendations for CRE colonization screening of high-risk individuals. CRE screening of exposed high-risk employees was conducted by the University of Pennsylvania Occupational Health service and PDPH. Human rectal swabs were analyzed at the Antibiotic Resistance Laboratory Network (ARLN) Maryland Laboratory. PDPH were invited to conduct an onsite infection control assessment and to suggest improvements. Results: No pet owners self-identified in high-risk groups to be screened. In total, 10 high-risk staff were screened, and no colonized individuals were detected. Recommendations made by the PDPH to MJRVH included improvement of infection prevention and control policies (eg, consolidation of the infection control manual and identification of lead staff member), improvement in hand hygiene (HH) compliance (eg, increasing amount of HH supplies), improvement of environment of care (eg, decluttering and evaluation of mulched animal relief area), and improvement of respiratory care processes (eg, standardization of care policies). MJRVH made substantial improvements across recommendation areas including revision of infection control manual, creation of a full-time infection preventionist position, individual alcohol hand sanitizers for patient cages, and environmental decluttering and decontamination. PDPH and MJRVH maintained frequent communication about infection control improvements. Conclusions: No positive transmission to high-risk staff members suggest that, like in human healthcare facilities, transmission of CRE to caretakers may not be a common event. Stronger communication and collaboration is required from Departments of Public Health (DPH) to the veterinary profession regarding the reporting requirements of emerging pathogens such as CRE. Veterinary facilities should view DPH as a valuable resource for recommendations to fill in gaps that exist in infection control “best practices,” particularly for novel pathogens in veterinary settings.
Disclosures: Jane M. Gould reports that her spouse receives salary from Incyte.
The coronavirus disease 2019 (COVID-19) has greatly impacted health-care systems worldwide, leading to an unprecedented rise in demand for health-care resources. In anticipation of an acute strain on established medical facilities in Dallas, Texas, federal officials worked in conjunction with local medical personnel to convert a convention center into a Federal Medical Station capable of caring for patients affected by COVID-19. A 200,000 square foot event space was designated as a direct patient care area, with surrounding spaces repurposed to house ancillary services. Given the highly transmissible nature of the novel coronavirus, the donning and doffing of personal protective equipment (PPE) was of particular importance for personnel staffing the facility. Furthermore, nationwide shortages in the availability of PPE necessitated the reuse of certain protective materials. This article seeks to delineate the procedures implemented regarding PPE in the setting of a COVID-19 disaster response shelter, including workspace flow, donning and doffing procedures, PPE conservation, and exposure event protocols.
The Minimal Data Set are demographic and tobacco use questions asked during enrollment at many quitlines. We tested whether these questions can be used to predict program engagement and success, and to evaluate whether findings can inform the tailoring of protocols to disparate populations. We analyzed 7,920 Arizona Smokers' Helpline treatment records to test a Structural Equation Model of the mediating effects of quitline services and short-term cessation outcomes on the relationship between intake questions and 7-month quit rate. Education (b = 0.05), gender (b = 0.03), Medicaid (b = −0.09), longest length of previous quit attempt (b = 0.05), confidence in quitting for 24 h (b = 0.04), environmental risk (b = −0.05), and life stress (b = 0.04) all significantly (P < 0.05) predicted engagement in quitline services. Program engagement had a direct effect on an in-program cessation outcomes construct (b = 0.47) and 7-month quit rate (b = 0.44). This in-program cessation outcomes construct had a significant direct effect on 7-month quit rate (b = −0.12). This model showing the relationship between program engagement and outcomes suggests that tailoring protocols can focus on engaging clients who have historically not taken full advantage of quitline services.
Apart from its role as a digestive and absorptive organ, the gastrointestinal (GI) tract is a vital immune organ that encompasses roughly 70 % of the total immune cells of the body. As such, the physical, chemical and nutrient composition of the diet influences overall GI function, effectively as an immune organ. With the improvement in feed technology, agro-industrial co-products that are high in fibre have been widely used as a feed ingredient in the diets of pigs and poultry. Arabinoxylan (AX) and mannan are the most abundant hemicellulosic polysaccharides present in cereal grain and co-product ingredients used in the livestock industry. When monogastric animals consume diets containing high amounts of AX and mannans, stimulation of GI immune cells may occur. This involves the activation of several cellular and molecular pathways of the immune system and requires a considerable amount of energy and nutrients to be expended by the animal, which may ultimately influence overall health and growth performance of animals. Therefore, a better understanding of the role of AX and mannan in immune modulation will be helpful in modulating untoward GI immune responses, thereby minimising nutrient and energy expenditure toward this effort. This review will summarise pertinent research on the role of oligosaccharides and polysaccharides containing AX and mannans in immune modulation in order to preserve gut integrity.
Introduced from Europe to North America in the early 19th century as an ornamental shrub and for medicinal purposes, common buckthorn (Rhamnus cathartica L.) has since spread and naturalized throughout regions of the United States and Canada. The purpose of this study was to investigate levels of genetic variation and population differentiation in R.cathartica in its introduced range in North America compared with its native range in Europe to better understand patterns of spread. By analyzing introduced and native populations using microsatellite markers, we found that introduced populations generally exhibited similar or slightly lower levels of genetic variation compared with native populations, consistent with a slight bottleneck effect. Introduced populations contained many different genotypes, indicating genetic admixture, rather than one or few genotypes. In a few cases, populations had been misidentified in the field and were glossy buckthorn (Frangula alnus Mill.; syn. Rhamnus frangula L.). Overall, there was no substantial genetic differentiation detected between native and introduced populations of R. cathartica. Invasive spread in this species is likely due to its past horticultural history as well as adaptive biological traits such as competitive behavior, potential allelopathy, and seed dispersal via birds.
The final question addressed in chapter three is one that continues to arise in practice and to engender debate: the authority of a truncated tribunal to proceed to issue a final award. The issue comes to the fore when a party-appointed arbitrator resigns or otherwise refuses to participate in panel deliberations, whether unilaterally or at the behest of his or her appointing party. The jurisprudence on this topic has developed significantly with the trend towards judicial (rather than diplomatic) arbitration, in large measure as a result of a series of decisions by the Iran-United States Claims Tribunal and the confrontation of this problem in arbitral rules. There is a discernible preference among tribunals, institutions, and scholars to replace the obstructionist arbitrator and thereby prevent the need for a truncated tribunal. Where this is not in the circumstances feasible, the authority of the remaining two members to proceed to a final determination is widely accepted. Either way, the trend has been to continue to fortify international arbitration against unilateral attempts to derail the proceedings.
One of the most striking features of arbitral practice over the past three decades has been how old problems have continued to arise in new guises. This is particularly apparent with the problem of States’ various attempts to negate arbitration, and whether denial of justice may be invoked to confront that practice. This issue is considered in the second chapter of this book. The practice since the time of the first edition of this book underscores that governmental evasion and negation of arbitration can take a number of forms. Arbitral tribunals, and in particular those constituted under bilateral investment treaties, have responded to new attempts at governmental negation of arbitration. The question today is not only whether a State’s refusal to arbitrate may constitute a denial of justice, but whether a State’s attempt to negate arbitration—by, for example, improperly setting aside an international award—may constitute a compensable expropriation of property rights, a breach of fair and equitable treatment, or another breach of an investment treaty.
The severability of the arbitration agreement, a cornerstone principle of international arbitration that is considered in the first chapter of this book, is more firmly established now than it was three decades ago. Yet respondents still from time to time call that principle into question by attempting to vitiate the arbitral process by invoking a (supposed) defect in the underlying contract or treaty, while difficult issues also remain concerning the precise scope and limits of the principle. These issues underscore the merit in analyzing and revisiting what remains a jurisprudentially subtle and practically important question.
The vitality or, alternatively, vitiation of the international arbitral process remains a pressing subject. The explosion of inter-State, investor-State, and international commercial arbitration in recent years magnifies the importance of the subject. This second edition combines the historical analysis of the first edition with a survey of the continued salience and contemporary developments for each of the three problems identified: (i) the severability of the arbitration agreement; (ii) denial of justice (and now other possible breaches of international law) by governmental negation of arbitration; and (iii) the authority of truncated international arbitral tribunals. The international arbitral process continues to be fortified against unilateral attempts to derail it and, to that end, this book will be a valuable guide for practitioners and scholars alike.
The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.
In a randomized, controlled trial, 271 mid-life adults (30–54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.
Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.
In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.
Creutzfeldt-Jakob disease (CJD) is a fatal neurological illness for which accurate diagnosis is paramount. Real-time quaking-induced conversion (RT-QuIC) is a prion-specific assay with high sensitivity and specificity for CJD. The Canadian endpoint quaking-induced conversion (EP-QuIC) test is similar, but unlike RT-QuIC there is little data regarding its diagnostic utility in clinical practice. In this exploratory predictive value analysis of EP-QuIC in CJD, the negative predictive value (NPV) and positive predictive value (PPV) was 100% and 83%, respectively, with one false-positive result identified. Re-testing this sample with an optimized EP-QuIC protocol eliminated this false-positive result, leading to a PPV of 100%.
Second language (L2) motivation as a field of research has expanded rapidly in recent years, attracting scholars from increasingly diverse educational contexts and theoretical perspectives. The move towards more learner-centred approaches in language education, together with an accompanying interest in the various contributions learners make to their own learning, pushed the study of motivation into a prominent position on the current research agenda. From a field consisting of a small group of researchers and a handful of infrequent articles in the 1980s, L2 motivation research has thrived (Boo, Dörnyei, & Ryan, 2015), with articles frequently appearing in leading journals and the field even meriting its own handbook (Lamb et al., forthcoming). Motivation, uniquely among the so-called language learner individual differences, has been enthusiastically embraced by both researchers and classroom practitioners, resulting in a fast-changing and rapidly expanding theoretical landscape.