Quorum sensing (QS) is under the control of N-acylated L-homoserine lactones (AHLs) and their cognate receptors (LuxR-type proteins) in Gram-negative bacteria, and plays a major role in mediating host-bacteria interactions by these species. Certain cyclic dipeptides (2,5-diketopiperazines, DKPs) have been isolated from bacteria and reported to activate or inhibit LuxRtype proteins in AHL biosensor strains, albeit at significantly higher concentrations than native lactones. These reports have prompted the proposal that DKPs represent a new class of QS signals, and potentially even interspecies or interkingdom signals; their mechanisms of action and physiological relevance, however, remain unknown. Here, we describe a library of synthetic DKPs that was designed to (1) determine the structural features necessary for LuxR-type protein activation and inhibition, and (2) probe their mechanisms of action. These DKPs, along with several previously reported natural DKPs, were screened in bacterial reporter gene assays. In contrast to previous reports, the native DKPs failed to exhibit either antagonistic or agonistic activities in these assays. However, non-natural halogenated cyclo(L-Pro-L-Phe) derivatives were capable of inhibiting luminescence in V. fischeri. Interestingly, additional experiments revealed that these DKPs do not compete with the natural lactone signal, OHHL, to inhibit luminescence. Together, these data suggest that DKPs are not QS signals in the bacteria examined in this study. Although these compounds can influence QS-regulated outcomes, we contend that they do not do so through direct interaction with LuxR-type proteins. This work serves to refine the lexicon of naturally occurring QS signals used by Gram-negative bacteria.

Approximately 370-500 million Indigenous people live worldwide. While Indigenous peoples make up only 5% of the world's population, they account for 15% of the extreme poor and have life expectancy that is 20 years shorter than that of non-Indigenous people. Access to healthcare has been identified as an important social determinant of health and key driver of health outcomes. Indigenous populations often face barriers to accessing healthcare including living in remote areas, lacking financial resources, and having cultural differences. Telehealth, the utililzation of any synchronous modality, including phone, video, or teleconferencing technology used to support the provision of long-distance health care and health education, is a feasible and cost-effective treatment delivery mechanism that has successfully addressed access barriers faced by vulnerable populations globally, however, few studies have included indigenous populations and the application of this technology to improve physical and mental health outcomes. This systematic review aims to identify trials that were conducted among Indigenous adults, and to summarize the components of interventions that have been found to effectively improve the health of Indigenous peoples.The PRISMA guidelines for reporting of systematic reviews were followed in preparing this manuscript.Studies were identified by searching PubMed, Scopus, and PsychInfo databases for clinical trial articles on Indigenous peoples and mental and physical health, published between January 1, 1998 and December 31, 2018. Eligibility criteria for determining studies to include in the analysis were as follows: (I) ≥18 years of age; (II) indigenous peoples; (III) any technology-based intervention; (IV) studies included at least one of the following mental health (depression, post-traumatic stress disorder, suicide) and physical health (mortality, blood pressure, hemoglobin A1C, cholesterol, quality of life) outcomes; (V) clinical trials. A total of 2,662 articles were identified and six were included in the final review based on pre-specified eligibility criteria.Three were conducted in the United States, one study was conducted in Canada, and two were conducted in New Zealand. Study sample sizes ranged from 20 to 762, intervention delivery times ranged from three to 20 months and utilized telephone, internet and SMS messaging as the type of technology. There is a paucity of evidence on the use of telehealth programs to increase access to chronic disease programs in Indigenous populations. This review highlights the importance of culturally tailoring programs despite the modality in which they are delivered, and recommends telephone-based delivery facilitated by a trained health professional. Telehealth has great promise for meeting the health needs of highly marginalized Indigenous populations around the world, however, at this point more research is needed to understand how best to structure and deliver these programs for maximum effect.

Background Small-bowel capsule endoscopy is advocated and repeat upper gastrointestinal (GI) endoscopy should be considered for evaluation of recurrent or refractory iron deficiency anemia (IDA). A new device that allows magnetic steering of the capsule around the stomach (magnetically assisted capsule endoscopy [MACE]), followed by passive small-bowel examination might satisfy both requirements in a single procedure. Methods In this prospective cohort study, MACE and esophagogastroduodenoscopy (EGD) were performed in patients with recurrent or refractory IDA. Comparisons of total (upper GI and small bowel) and upper GI diagnostic yields, gastric mucosal visibility, and patient comfort scores were the primary end points. Results 49 patients were recruited (median age 64 years; 39 % male). Combined upper and small-bowel examination using the new capsule yielded more pathology than EGD alone (113 vs. 52; P < 0.001). In upper GI examination (proximal to the second part of the duodenum, D2), MACE identified more total lesions than EGD (88 vs. 52; P < 0.001). There was also a difference if only IDA-associated lesions (esophagitis, altered/fresh blood, angioectasia, ulcers, and villous atrophy) were included (20 vs. 10; P = 0.04). Pathology distal to D2 was identified in 17 patients (34.7 %). Median scores (0 – 10 for none – extreme) for pain (0 vs. 2), discomfort (0 vs. 3), and distress (0 vs. 4) were lower for MACE than for EGD (P < 0.001). Conclusion Combined examination of the upper GI tract and small bowel using the MACE capsule detected more pathology than EGD alone in patients with recurrent or refractory IDA. MACE also had a higher diagnostic yield than EGD in the upper GI tract and was better tolerated by patients.

Background Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. Design Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. Methods Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, Scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICER) of POC-VL compared to CD4 and clinical monitoring. Results POC-VL tests with detection limits <1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5–US$20 and detection limits between 1000 and 10000 copies/ml, the ICER of POC-VL was US$4010–US$9230 compared to clinical and US$5960–US$25540 compared to CD4 monitoring. In Scenario B the corresponding ICERs were US$2450–US$5830 and US$2230–US$10380. In Scenario C the ICER ranged between US$960–US$2500 compared to clinical monitoring and between cost-saving and US$2460 compared to CD4 monitoring. Conclusions The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and when assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Infection by a parasite often induces behavioural changes in the host and these changes may benefit either the host or the parasite. However, whether these changes are active host defence mechanisms or parasitic manipulations or simply incidental byproducts of the infection is not always clear. It has been suggested that understanding the proximate mechanisms of these changes as well as comparative studies could help distinguish these alternatives better. Behavioural fever is a common response to an infection in many animals and we investigated the phenomenon in the novel host-parasite relationship between the honeybee and the temperature-sensitive microsporidian Nosema ceranae. Our results show that infected bees prefer higher temperatures and even though this seems to benefit the pathogen, the proximate mechanism underlying this change is the pathological stress underlying the infection. Especially because it is a new host-parasite relationship, it is best to label the observed behavioural change as a case of incidental benefit although this does not rule out selection acting on it. We discuss the importance of looking at the behavioural outcomes of host-parasite relationships and the importance of studying them at multiple levels for understanding their origin and maintenance.