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Circulating cell-free DNA (ccf-DNA) is becoming an important biomarker for cancer diagnostics and therapy monitoring. The isolation of ccf-DNA from plasma as a \"liquid biopsy\" may begin to replace more invasive tissue biopsies for the detection and analysis of cancer-related mutations. Conventional methods for the isolation of ccf-DNA from plasma are costly, time-consuming, and complex, preventing the use of ccf-DNA biomarkers for point-of-care diagnostics and limiting other biomedical research applications. We used an AC electrokinetic device to rapidly isolate ccf-DNA from 25 μL unprocessed blood. ccf-DNA from 15 chronic lymphocytic leukemia (CLL) patients and 3 healthy individuals was separated into dielectrophoretic (DEP) high-field regions, after which other blood components were removed by a fluidic wash. Concentrated ccf-DNA was detected by fluorescence and eluted for quantification, PCR, and DNA sequencing. The complete process, blood to PCR, required <10 min. ccf-DNA was amplified by PCR with immunoglobulin heavy chain variable region (IGHV)-specific primers to identify the unique IGHV gene expressed by the leukemic B-cell clone, and then sequenced. PCR and DNA sequencing results obtained by DEP from 25 μL CLL blood matched results obtained by use of conventional methods for ccf-DNA isolation from 1 mL plasma and for genomic DNA isolation from CLL patient leukemic B cells isolated from 15-20 mL blood. Rapid isolation of ccf-DNA directly from a drop of blood will advance disease-related biomarker research, accelerate the transition from tissue to liquid biopsies, and enable point-of-care diagnostic systems for patient monitoring.

Pulmonary damage by Pseudomonas aeruginosa during cystic fibrosis lung infection and ventilator-associated pneumonia is mediated both by pathogen virulence factors and host inflammation. Impaired immune function due to tissue damage and inflammation, coupled with pathogen multidrug resistance, complicates management of these deep-seated infections. Therefore, preservation of lung function and effective immune clearance may be enhanced by selectively controlling inflammation. Pathological inflammation during P. aeruginosa pneumonia is driven by interleukin-1β (IL-1β). This proinflammatory cytokine is canonically regulated by caspase-family inflammasome proteases, but we report that plasticity in IL-1β proteolytic activation allows for its direct maturation by the pseudomonal protease LasB. LasB promotes IL-1β activation, neutrophilic inflammation, and destruction of lung architecture characteristic of severe P. aeruginosa pulmonary infection. Discovery of this IL-1β regulatory mechanism provides a distinct target for anti-inflammatory therapeutics, such that matrix metalloprotease inhibitors blocking LasB limit inflammation and pathology during P. aeruginosa pulmonary infections. IL-1β drives pathology during pulmonary infection by Pseudomonas aeruginosa. The Pseudomonas protease LasB cleaves and activates IL-1β independent of canonical and noncanonical inflammasomes Metalloprotease inhibitors active against LasB limit inflammation and bacterial growth Inflammation is highly damaging during lung infections by the opportunistic pathogen Pseudomonas aeruginosa. Sun et al. demonstrate that the Pseudomonas LasB protease directly activates IL-1β in an inflammasome-independent manner. Inhibition of IL-1β conversion by LasB protects against neutrophilic inflammation and destruction of the lung. Adjunctive therapeutics that limit pathological inflammation induced by infection would be beneficial for the treatment of pulmonary infections when used with conventional antibiotics.

In 2025, the province of British Columbia (BC), Canada, experienced heightened measles activity, mostly involving unvaccinated communities. Publicly funded measles vaccination for children aged 12 months has been routine since 1969, with a second dose at age 18 months added in 1996, and rescheduled to 4 to 6 years (school entry) in 2012. We aimed to assess population-based measles seroprevalence in relation to historic measles endemicity and vaccination considerations. In August 2024, we undertook a cross-sectional serosurvey, testing more than 1000 anonymized residual sera for measles antibody. We collected sera from outpatients attending a laboratory network in the Lower Mainland, BC, with equal numbers from 10 age groups, from 1 year to older than 80 years. Measles seropositivity was 89% (95% confidence interval [CI] 87% to 91%) overall and 93% (95% CI 91% to 94%) if equivocal results were also considered positive. Seropositivity was 90% or higher in all age groups except 10- to 19-year-olds (82% [95% CI 74% to 89%]), 20- to 29-year-olds (69% [95% CI 59% to 78%]), and 30- to 39-year-olds (73% [95% CI 63% to 81%]). Results remained below 80% for 20- to 39-year-olds, and significantly below all other age groups, even considering equivocal results as positive. In birth cohort analysis, seropositivity appeared lower among those due for their second vaccine dose during the COVID-19 pandemic or born during the postvaccination era to mothers with a higher likelihood of previous infection when measles was endemic. Our measles serosurvey findings inform vaccine coverage and complement other case-based surveillance indicating robust population-level immunity outside of unvaccinated clusters or communities. In addition to showing age-related antibody decline, serosurveillance provides insights into potential cohort effects that may have implications for vaccination programs.

Degradative enzyme activity has been shown to be elevated in many diseases including shock, diabetes, schizophrenia, several types of cancers, and coagulation disorders. The ability to measure degradative enzyme activity in whole blood and other complex samples would be useful for the development of rapid clinical diagnostics, the elucidation of disease progression, and the design of therapeutics. Current techniques to measure degradative enzyme activity require considerable amounts of time and sample processing steps. In this dissertation, a novel method for rapid detection of degradative enzyme activity, specifically protease activity, in whole blood is applied to several disease states: diabetes, schizophrenia, and premature neonates.

Large immunization clinics are commonly held to deliver influenza vaccine to seniors and others. Vaccine is typically dispensed from multi-dose vials but pre-filled syringes are now available, offering time savings for vaccinators. To determine if the higher purchase price of such syringes is offset by savings in time and injection supplies, we did a controlled comparison of syringe and vial formats in two large, concurrent, community-based influenza vaccination clinics. Vaccine preparation and immunization times were carefully documented along with costs for vaccine purchase, storage and injection supplies. Servicing 1,000 clients required 27 nurse hours using syringes and 36 hours using vials but the savings for personnel ($234) and supplies ($1,190) using syringes were exceeded by higher vaccine cost ($2,090 premium) and extra storage costs ($260) for bulkier packaging. Depending upon product and packaging style, programs using vials are cheaper by $709-$926 per 100 doses delivered compared to using pre-filled syringes. Des campagnes de vaccination à grande échelle contre l'influenza sont régulièrement proposées aux personnes âgées et autres populations à risque. Le vaccin est généralement administré à partir de flacons multidoses mais des seringues préremplies sont maintenant disponibles, offrant un gain de temps aux employés réalisant les vaccinations. Afin de déterminer si le prix d'achat plus élevé de ces seringues est compensé par des économies en temps et en matériel d'injection, nous avons réalisé une étude contrôlée comparant les seringues préremplies aux flacons multidoses lors de deux grandes campagnes simultanées de vaccination contre l'influenza. Le temps nécessaire à la préparation et à l'injection du vaccin ainsi que le prix d'achat et de stockage du vaccin et du matériel d'injection ont été documentés avec soin. L'administration du vaccin à 1 000 clients a nécessité 27 heures de temps infirmier pour le système utilisant les seringues contre 36 heures pour le système utilisant les flacons. Cependant, ce bénéfice en personnel (234$) et en matériel (1190$) a été absorbé par le prix plus élevé du vaccin (2090$) et le coût supplémentaire lié au stockage d'un plus grand volume (260$). Selon le type de produit et d'emballage utilisé, les programmes utilisant les flacons représentent une économie de 709$-926$ pour 100 doses administrées par rapport aux programmes utilisant les seringues préremplies.