One of the major challenges the scientific community faces today is the lack of translational data generated from mouse trials for human health application. Housing temperature-dependent chronic cold stress in laboratory rodents is one of the key factors contributing to lack of translatability because it reveals major metabolic differences between humans and rodents. While humans tend to operate at temperatures within their thermoneutral zone, most laboratory rodents are housed at temperatures below this zone and have an increased energy demand to generate heat. This has an impact on the immune system of mice and thus affects results obtained using murine models of human diseases. A limited number of studies and reviews have shown that results obtained on mice housed at thermoneutrality were different from those obtained from mice housed in traditional housing conditions. Most of those studies, focused on obesity and cancer, found that housing mice at thermoneutrality changed the outcomes of the diseases negatively and positively, respectively. In this review, we describe how thermoneutrality impacts the immune system of rodents generally and in the context of different disease models. We show that thermoneutrality exacerbates cardiovascular and auto-immune diseases; alleviates asthma and Alzheimer’s disease; and, changes gut microbiome populations. We also show that thermoneutrality can have exacerbating or alleviating effects on the outcome of infectious diseases. Thus, we join the call of others in this field to urge researchers to refine murine models of disease and increase their translational capacity by considering housing at thermoneutrality for trials involving rodents.

BackgroundChlamydia trachomatis(CT) andNeisseria gonorrhoeae(GC) resulted in over 200 million new sexually transmitted infections last year. Self-sampling strategies alone or combined with digital innovations (ie, online, mobile or computing technologies supporting self-sampling) could improve screening methods. Evidence on all outcomes has not yet been synthesised, so we conducted a systematic review and meta-analysis to address this limitation.MethodsWe searched three databases (period: 1 January 2000–6 January 2023) for reports on self-sampling for CT/GC testing. Outcomes considered for inclusion were: accuracy, feasibility, patient-centred and impact (ie, changes in linkage to care, first-time testers, uptake, turnaround time or referrals attributable to self-sampling).We used bivariate regression models to meta-analyse accuracy measures from self-sampled CT/GC tests and obtain pooled sensitivity/specificity estimates. We assessed quality with Cochrane Risk of Bias Tool-2, Newcastle–Ottawa Scale and Quality Assessment of Diagnostic Accuracy Studies-2 tool.ResultsWe summarised results from 45 studies reporting self-sampling alone (73.3%; 33 of 45) or combined with digital innovations (26.7%; 12 of 45) conducted in 10 high-income (HICs; n=34) and 8 low/middle-income countries (LMICs; n=11). 95.6% (43 of 45) were observational, while 4.4% (2 of 45) were randomised clinical trials.We noted that pooled sensitivity (n=13) for CT/GC was higher in extragenital self-sampling (>91.6% (86.0%–95.1%)) than in vaginal self-sampling (79.6% (62.1%–90.3%)), while pooled specificity remained high (>99.0% (98.2%–99.5%)).Participants found self-sampling highly acceptable (80.0%–100.0%; n=24), but preference varied (23.1%–83.0%; n=16).Self-sampling reached 51.0%–70.0% (n=3) of first-time testers and resulted in 89.0%–100.0% (n=3) linkages to care. Digital innovations led to 65.0%–92% engagement and 43.8%–57.1% kit return rates (n=3).Quality of studies varied.DiscussionSelf-sampling had mixed sensitivity, reached first-time testers and was accepted with high linkages to care. We recommend self-sampling for CT/GC in HICs but additional evaluations in LMICs. Digital innovations impacted engagement and may reduce disease burden in hard-to-reach populations.PROSPERO registration numberCRD42021262950.

IntroductionMost studies using murine disease models are conducted at housing temperatures (20 – 22°C) that are sub-optimal (ST) for mice, eliciting changes in metabolism and response to disease. Experiments performed at a thermoneutral temperature (TT; 28 – 31°C) have revealed an altered immune response to pathogens and experimental treatments in murine disease model that have implications for their translation to clinical research. How such conditions affect the inflammatory response to infection with Plasmodium berghei ANKA (PbA) and disease progression is unknown. We hypothesized that changes in environmental temperature modulate immune cells and modify host response to malaria disease. To test this hypothesis, we conducted experiments to determine: (1) the inflammatory response to malarial agents injection in a peritonitis model and (2) disease progression in PbA-infected mice at TT compared to ST.MethodsIn one study, acclimatized mice were injected intraperitoneally with native hemozoin (nHZ) or Leishmania at TT (28 – 31°C) or ST, and immune cells, cytokine, and extracellular vesicle (EV) profiles were determined from the peritoneal cavity (PEC) fluid. In another study, PbA-infected mice were monitored until end-point (i.e. experimental malaria score ≥4).ResultsWe found that Leishmania injection resulted in decreased cell recruitment and higher phagocytosis of nHZ in mice housed at TT. We found 398 upregulated and 293 downregulated proinflammatory genes in mice injected with nHZ, at both temperatures. We report the presence of host-derived EVs never reported before in a murine parasitic murine model at both temperatures. We observed metabolic changes in mice housed at TT, but these did not result to noticeable changes in disease progression compared to ST.DiscussionTo our knowledge, these experiments are the first to investigate the effect of thermoneutrality on a malaria murine model. We found important metabolic difference in mice housed at TT. Our results offer insights on how thermoneutrality might impact a severe malaria murine model and directions for more targeted investigations.