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In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta–gonad–mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM. Specific chemical and inducible genetic depletion of macrophages or inhibition of matrix metalloproteinases (Mmps) leads to an accumulation of HSPCs in the AGM and a decrease in the colonization of haematopoietic organs. Finally, in vivo zymography demonstrates the function of primitive macrophages in extracellular matrix degradation, which allows HSPC migration through the AGM stroma, their intravasation, leading to the colonization of haematopoietic organs and the establishment of definitive haematopoiesis. Haematopoietic stem/progenitor cells (HSPCs) transform from aortic endothelium into migratory cells that move through stroma and enter circulation to colonize haematopoietic tissues. Here the authors show that HSPCs' passage is facilitated by primitive macrophages that secrete extracellular matrix-degrading enzymes.

Material arriving at our solar system from the Galaxy may be detected on Earth in the form of meteors ablating in our atmosphere. Here, we report on a search for interstellar meteors within the highest-quality events in the Global Meteor Network (GMN) database. No events were detected that were conclusively hyperbolic with respect to the Sun; however, our search was not exhaustive and examined only the top 57% of events, with a deeper examination planned for future work. This study’s effective meteoroid mass limit is 6.6 ± 0.8 × 10−5 kg (5 mm diameter at a density of 1000 kg m−3). Theoretical rates of interstellar meteors at these sizes range from 3 to 200 events globally per year. The highest rates can already be largely excluded by this study, while at the lowest rates, GMN would have to observe for 25 more years to be 50% confident of seeing at least one event. GMN is thus well-positioned to provide substantial constraints on the interstellar population at these sizes over the coming years. This study’s results are statistically compatible with a rate of interstellar meteors at the Earth at less than 1 per million meteoroid impacts at Earth at millimeter sizes, or a flux rate of less than 8 ± 2 × 10−11 km−2 hr−1 at the 95% confidence level.

Background: Research indicates that education on sun protection and proper sunscreen application is insufficient, leading to widespread under-application of sunscreen. This lack of adherence to recommended practices increases the risk of skin cancers, photoageing and exacerbates conditions like melasma and lupus. Objective: This review aims to provide clinicians with a practical framework to educate patients on effective sun protection, including sunscreen use, and to address common barriers to adherence. Discussion: Sunscreen is crucial for preventing melanoma, non-melanoma skin cancers, photoageing and exacerbating conditions like melasma and lupus. Despite its importance, it is often underapplied. Effective patient education is essential, and clinicians are well positioned to guide effective sunscreen use and encourage holistic sun protection behaviours. In addition to sunscreen, this includes wearing protective clothing, broad-brimmed hats, sunglasses and seeking shade.

The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings. To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing. All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance. From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as \"false positives\" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal). Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing.

We inspected 16S rRNA sequences of 784 publicly available Treponema pallidum subspecies pallidum genomes and 17 new T. pallidum subsp. pallidum genomes from Canada for putative mutations associated with doxycycline resistance. Variants were detected in 9 non-Canada genomes. These findings establish a global genomic baseline for monitoring doxycycline resistance in syphilis.

Background Syphilis now affects every population and serology is the mainstay of diagnosis. The issue is that serology has a turnaround time of several days. One solution is point-of-care tests (POCTs), which can provide results in minutes. We consequently evaluated the MedMira Multiplo® Complete Syphilis Test in an STI clinic in Ottawa, Canada. Methods Anyone 16 + years old who consented and was undergoing syphilis testing at our clinic was eligible. Those who enrolled completed the POCT and saw a clinician to review their result. We calculated sensitivities and specificities for the POCT, compared to serology and diagnosis. Results From August 2024 to May 2025, we performed 622 syphilis POCTs on 600 participants. Compared to serology when chemiluminescent microparticle immunoassay (CMIA) and Treponema pallidum particle agglutination (TP.PA) tests were reactive, the POCT treponemal (TP) test had a sensitivity of 90.1% and specificity of 97.9%. Compared to any dilution of rapid plasma reagin (RPR), the POCT non-treponemal (nTP) test had a sensitivity of 82.5% and specificity of 99.1%. When we stratified POCT nTP results based on RPR titers, the POCT nTP had a sensitivity of 94.1% for RPR dilutions ≥ 1:8. Compared to serology, the POCT identified 91.4% of new syphilis infections and 97% of infectious syphilis. Conclusions POCTs informed clinical syphilis management. While most research has focused on how POCTs can facilitate treatment, in our study, there was a second major utility: to withhold antibiotics when recommended as empiric treatment but when the patient does not have active syphilis. Future research on syphilis POCTs should focus on their abilities to rule in and rule out infections. Trial registration NCT06586905 (Registered Sept 4, 2024).

Objectives In 2014, Ontario’s Point-of-Care (POC) test providers were advised to focus efforts on provincially defined priority populations who experience a greater risk of HIV. Our objective was to describe the POC program before, during and after this change, including tester characteristics, follow-up testing results, positive predictive value (PPV) over time, and trends and characteristics of those with reactive test results without a confirmatory serological specimen. Methods Test-level data of POC screening and confirmatory results were extracted from the Public Health Ontario HIV Datamart. Final test results were defined based on results of the confirmatory blood sample, or the POC test for “non-reactive” tests. Testing volumes, percent of total tests, percent positivity and PPV were calculated overall, annually, and by exposure group. Results Overall testing volumes decreased by 39.8% between 2014 and 2018. The majority of confirmed positive tests were in the men who have sex with men (MSM) exposure category, followed by HIV-endemic and heterosexual – no identified risk (heterosexual—NIR). Overall percent positivity decreased from 0.59% in 2011 to 0.42% in 2015 (change of 0.17%, 95% CI 0.03% to 0.31%), increasing to 0.69% in 2018 (change of 0.27%, 95% CI 0.20% to 0.34%). Increases in percent positivity corresponded with a decrease in the overall proportion of tests conducted in low-risk populations. When compared to the heterosexual-NIR category, PPV was significantly higher for men who have sex with men – people who use injection drugs (MSM-PWID) (52.7% compared to 100%, P  < .001), MSM (52.7% compared to 95.4%, P  < .001), HIV-endemic (52.7% compared to 91.5%, P  < .001), heterosexual – partner with identified risk (heterosexual—PIR) (52.7% compared to 77.3%, P  = .042), and people who use injection drugs (PWID) (52.7% compared to 81.3%, P  = 0.007). A total of 13.5% of reactive POC results did not have a serological sample submitted. Conclusions Targeted testing towards populations at higher risk of HIV improved the overall test performance characteristics of Ontario’s POC testing program. While not unexpected, the large discrepancies between PPV in higher-risk, compared to lower-risk populations, suggests the need for greater awareness and messaging of the likelihood of false positive test results in different populations.

Malaria in pregnancy is associated with adverse birth outcomes. However, the underlying mechanisms remain poorly understood. Tight regulation of angiogenic, metabolic, and inflammatory pathways are essential for healthy pregnancies. We hypothesized that malaria disrupts these pathways leading to preterm birth (PTB). We conducted a secondary analysis of a randomized trial of malaria prevention in pregnancy conducted in Malawi from July 21, 2011, to March 18, 2013. We longitudinally assessed circulating mediators of angiogenic, metabolic, and inflammatory pathways during pregnancy in a cohort of HIV-negative women (n = 1,628), with a median age of 21 years [18, 25], and 562 (35%) were primigravid. Pregnancies were ultrasound dated, and samples were analyzed at 13 to 23 weeks (Visit 1), 28 to 33 weeks (Visit 2), and/or 34 to 36 weeks (Visit 3). Malaria prevalence was high; 70% (n = 1,138) had PCR-positive Plasmodium falciparum infection at least once over the course of pregnancy and/or positive placental histology. The risk of delivering preterm in the entire cohort was 20% (n = 304/1506). Women with malaria before 24 weeks gestation had a higher risk of PTB (24% versus 18%, p = 0.005; adjusted relative risk [aRR] 1.30, 95% confidence interval [CI] 1.04-1.63, p = 0.021); and those who were malaria positive only before week 24 had an even greater risk of PTB (28% versus 17%, p = 0.02; with an aRR of 1.67, 95% CI 1.20-2.30, p = 0.002). Using linear mixed-effects modeling, malaria before 24 weeks gestation was associated with altered kinetics of inflammatory (C-Reactive Protein [CRP], Chitinase 3-like protein-1 [CHI3L1], Interleukin 18 Binding Protein [IL-18BP], soluble Tumor Necrosis Factor receptor II [sTNFRII], soluble Intercellular Adhesion Molecule-1 [sICAM-1]), angiogenic (soluble Endoglin [sEng]), and metabolic mediators (Leptin, Angiopoietin-like 3 [Angptl3]) over the course of pregnancy (χ2 > 13.0, p ≤ 0.001 for each). Limitations include being underpowered to assess the impact on nonviable births, being unable to assess women who had not received any antimalarials, and, because of the exposure to antimalarials in the second trimester, there were limited numbers of malaria infections late in pregnancy. Current interventions for the prevention of malaria in pregnancy are initiated at the first antenatal visit, usually in the second trimester. In this study, we found that many women are already malaria-infected by their first visit. Malaria infection before 24 weeks gestation was associated with dysregulation of essential regulators of angiogenesis, metabolism, and inflammation and an increased risk of PTB. Preventing malaria earlier in pregnancy may reduce placental dysfunction and thereby improve birth outcomes in malaria-endemic settings.

Triggering receptor expressed on myeloid cells 1 (TREM1) is a cell-surface receptor expressed on neutrophils that amplifies the inflammatory response. Dengue virus (DENV) infection is characterized by systemic inflammation, endothelial activation, and vascular leakage. We investigated circulating soluble TREM-1 (sTREM-1) levels in 244 children and young adults aged 1-26 years with dengue fever presenting to an outpatient clinic in the Philippines. Elevated sTREM-1 (≥130 pg/mL) was associated with hemoconcentration, a hallmark of vascular leakage (odds ratio (OR) 3.8, 95%CI 1.6-10, p = 0.0020). In turn, hemoconcentration was associated with hospitalization (OR 4.2, 95%CI 1.0-38, p = 0.0497) and higher volume of intravenous fluid required for resuscitation (p = 0.019). Elevated inflammation marker TNF (≥5 pg/mL) was associated with increased sTREM-1 levels (p = 0.0014). Endothelial activation markers angiopoietin-2 (Ang-2), soluble FMS-like tyrosine kinase-1 (sFlt-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were correlated with sTREM-1 levels (p < 0.0001 for all three comparisons). Our findings suggest that sTREM-1 may be a clinically informative marker of neutrophil activation, associated with hemoconcentration, systemic inflammation, and endothelial activation and in dengue fever.

In an ambulatory multiple myeloma clinic covering 10 physicians that sends approximately 4,000 Immunomodulatory drugs (IMIDs) refills per year by a team of 8 Advanced Practice Providers (APPs) and 10 Registered Nurses (RNs), communication alignment for refill requests was challenging due to high medication refill volume and multiple modalities of communication. Original workflow included a RN receiving medication refill notification via EPIC In Basket. The RN would add the refill request to a manually managed shared Excel sheet for APPs to review or send an email to all APPs. Historically, there were 1-3 patient complaints per month regarding missed IMID refills as a result of missed communication. The purpose was to create a digitized and automated work queue to streamline interdisciplinary communication of IMID refill requests while simultaneously tracking and collecting data for auditing, analysis, administrative and managerial purposes. After initial process analysis, building rapport and buy-in with end-users, Microsoft Lists (a PHI-secure platform) was used to replicate previous Excel workflow with new automated features. The project was independent of an IT team. Design and implementation of the beta version was achieve in one day. Changes, updates and full user integration was achieved in one week. The platform tracks patient identifiers, physician, provider sending refill, medication, dose, quantity, direction, notes, authorization number, pharmacy, date added, date modified and total medications sent, not approved or pending. Since implementation, data entry has been self-sustained by end-users with 100% participation occurring on a daily basis. Patient complaints of missed refills have been at 0% post implementation. The RNs and APPs using the platform will be surveyed on ease of usability at 6 months. Data captured will be used for administrative and management purposes. This medication refill platform was a no-cost, secure, quick and effective implementation that improved workflow and streamlined communication between RNs and APPs. The platform tracks and collects data that can be used for additional research and process improvement initiatives. This platform can be replicated in other oncology practices. Innovative use of technology and informatics provided the opportunity for nurses to facilitate communication alignment between RNs and providers, improved coordination of patient care and track metrics for future analysis and process improvement; which can lead to improved patient medication adherence, decreased medication errors and increased patient satisfaction.