Impact of blood volume, air exposure duration, transport duration, and testing delay on plasma total carbon dioxide in simulated open collections using microtainers.

BACKGROUND: Exposing blood specimens to air reduces plasma total carbon dioxide (TCO2). We evaluated the degree of TCO2 reduction in simulated open collection of neonatal blood in BD microtainers® (microtainers), microtainer transport duration and delayed testing of open plasma aliquots. METHODS: Venous blood was aliquoted into open microtainers in a 3x4 factorial design to simulate combined effects of blood volume (0.2-0.6 mL) and air exposure duration (0-5 min), with blood drawn in vacutainers as a control. Separate effects of in-hospital transport duration (0-120 min; whole blood), off-site transport duration (0-24 h; centrifuged whole blood), and duration plasma aliquots remained open (0-120 min) were evaluated by repeated testing. Findings were analyzed using repeated-measures ANOVA and Student's T-tests. RESULTS: In the factorial experiment, mean plasma TCO2 in all microtainers was on average 3.5 mmol/L lower than in vacutainers. Smaller blood volume but not greater air exposure duration significantly (p < 0.05) reduced TCO2. Mean TCO2 in filled (0.6 mL; 1-5 min air exposure) microtainers was on average 2.9 mmol/L lower than in vacutainers. Simulated off-site transport of microtainers containing centrifuged whole blood significantly reduced TCO2 (4 h; mean -1.5 mmol/L), as did delayed testing of aliquoted plasma (15 min; mean -1.3 mmol/L). CONCLUSIONS: Plasma TCO2 decreased with reduced microtainer blood volume, extended transport duration of centrifuged blood and testing delay of aliquoted plasma. To minimize TCO2 reduction, microtainers should be fully filled and tested rapidly. Laboratories should also consider whether an interpretive comment, correction factor or separate reference intervals are appropriate for these tests.

Bridging Language Barriers in COVID-19 Research: Descriptive Study of AccesoCovid.com's Reach and User Engagement.

BACKGROUND: The COVID-19 pandemic underscored the challenge of swiftly disseminating research findings to a global audience. Language barriers further exacerbated disparities in access to timely scientific information, particularly for non-English speaking communities. The majority of COVID-19 research was published in English, limiting accessibility for Spanish-speaking populations. OBJECTIVE: This paper aims to assess the reach and effectiveness of AccesoCovid.com, a platform designed to disseminate up-to-date COVID-19 research in both English and Spanish, addressing the language gap in scientific communication. METHODS: AccesoCovid.com was developed through a partnership between the University of California, San Francisco (UCSF) and Universidad Nacional Autónoma de México (UNAM). The website's performance and user engagement were evaluated using Google Analytics over a span of 2 years. Key metrics included user language preference, geographical distribution, and site traffic. The website summarized and translated 1032 articles on various COVID-19 topics, such as "Pharmaceutical Interventions and Vaccines." RESULTS: From February 2021 to February 2023, the platform attracted 57,000 users. Of the 43,000 unique new visitors, 84.2% (n=36,219) hailed from Spanish-speaking regions. The majority accessed the site organically through search engines, with 88.4% (n=38,000) of users arriving this way, while 5000 (11.6%) users accessed the site directly. Most users (n=30,894, 72.1%) preferred the Spanish version of the site. The website's most accessed category was "Pharmaceutical Interventions and Vaccines," followed by "Clinical Presentation and Management" and "Mental Health." Regarding language distribution, 72.1% (n=30,894) of users primarily used Spanish; 21.4% (n=9215) used English; and 6.7% (n=2891) spoke other languages, including Portuguese, Chinese, and German. Geographically, the website attracted visitors from 179 countries, with the highest visitor counts from Mexico (n=12,342, 28.7%), Spain (n=6405, 14.9%), the United States (n=4416, 10.3%), and Peru (n=3821, 8.9%). CONCLUSIONS: AccesoCovid.com successfully bridged a critical language gap in the dissemination of COVID-19 research. Its success underscores the pressing need for multilingual scientific resources. The platform demonstrated significant user engagement and reach, particularly in Spanish-speaking countries. This highlights the potential for similar platforms to ensure equitable access to scientific knowledge across diverse linguistic communities. Future efforts should focus on expanding to other languages and conducting formal evaluations to enhance user satisfaction and impact.

Protein-Induced DNA Dumbbell Amplification (PINDA) and its applications to food hazards detection.

Quantification of trace amounts of proteins is technically challenging because proteins cannot be directly amplified like nucleic acids. To improve the analytical sensitivity and to complement conventional protein analysis methods, we developed a highly sensitive and homogeneous detection strategy called Protein-Induced DNA Dumbbell Amplification (PINDA). PINDA combines protein recognition with exponential nucleic acid amplification by using protein binding probes made of DNA strands conjugated to protein affinity ligands. When a pair of probes bind to the same target protein, complementary nucleic acid sequences that are conjugated to each probe are brought into close proximity. The increased local concentration of the probes results in the formation of a stable dumbbell structure of the nucleic acids. The DNA dumbbell is readily amplifiable exponentially using techniques such as loop-mediated isothermal amplification. The PINDA assay eliminates the need for washing or separation steps, and is suitable for on-site applications. Detection of the model protein, thrombin, has a linear range of 10 fM-100 pM and detection limit of 10 fM. The PINDA technique is successfully applied to the analysis of dairy samples for the detection of ß-lactoglobulin, a common food allergen, and Salmonella enteritidis, a foodborne pathogenic bacterium. The PINDA assay can be easily modified to detect other targets by changing the affinity ligands used to bind to the specific targets.

Separation of reproductive decline from lifespan extension during methionine restriction.

Lifespan-extending interventions are generally thought to result in reduced fecundity. The generality of this principle and how it may extend to nutrition and metabolism is not understood. We considered dietary methionine restriction (MR), a lifespan-extending intervention linked to Mediterranean and plant-based diets. Using a chemically defined diet that we developed for Drosophila melanogaster, we surveyed the nutritional landscape in the background of MR and found that folic acid, a vitamin linked to one-carbon metabolism, notably was the lone nutrient that restored reproductive capacity while maintaining lifespan extension. In vivo isotope tracing, metabolomics and flux analysis identified the tricarboxylic cycle and redox coupling as major determinants of the MR-folic acid benefits, in part, as they related to sperm function. Together these findings suggest that dietary interventions optimized for longevity may be separable from adverse effects such as reproductive decline.

Interruptions in HIV and Behavioral Health Care for Criminal-Legal Involved People Living with HIV Following Implementation of Decarceration and Shelter in Place in San Francisco, California.

Decarceration policies, enacted for SARS-CoV-2 mitigation in carceral settings, potentially exacerbated barriers to care for people living with HIV (PWH) with criminal legal involvement (CLI) during Shelter-in-Place (SIP) by limiting opportunities for engagement in provisions of HIV and behavioral health care. We compared health care engagement for PWH with CLI in San Francisco, California before and after decarceration and SIP using interrupted time series analyses. Administrative data identified PWH booked at the San Francisco County Jail with at least one clinic encounter from 01/01/2018-03/31/2020 within the municipal health care network. Monthly proportions of HIV, substance use, psychiatric and acute care encounters before (05/01/2019-02/29/2020) and after (03/01/2020-12/31/2020) SIP and decarceration were compared using Generalized Estimating Equation (GEE) log-binomial and logistic regression models, clustering on the patient-level. Of 436 patients, mean age was 43 years (standard-deviation 11); 88% cisgender-male; 39% white, 66% homeless; 67% had trimorbidity by Elixhauser score (medical comorbidity, psychotic disorder or depression, and substance use disorder). Clinical encounters immediately dropped following SIP for HIV (aOR = 0.77; 95% CI: 0.67, 0.90) and substance use visits (aRR = 0.83; 95% CI: 0.70, 0.99) and declined in subsequent months. Differential reductions in clinical encounters were seen among Black/African Americans (aRR = 0.93; 95% CI: 0.88, 0.99) and people experiencing homelessness (aRR = 0.92; 95% CI: 0.87, 0.98). Significant reductions in care were observed for PWH with CLI during the COVID-19 pandemic, particularly among Black/African Americans and people experiencing homelessness. Strategies to End the HIV Epidemic must improve engagement across diverse care settings to improve outcomes for this key population.

The Use of Model Cellulose Materials for Studying Molecular Interactions at Cellulose Interfaces.

Despite extensive research on biobased and fiber-based materials, fundamental questions regarding the molecular processes governing fiber-fiber interactions remain unanswered. In this study, we introduce a method to examine and clarify molecular interactions within fiber-fiber joints using precisely characterized model materials, i.e., regenerated cellulose gel beads with nanometer-smooth surfaces. By physically modifying these materials and drying them together to create model joints, we can investigate the mechanisms responsible for joining cellulose surfaces and how this affects adhesion in both dry and wet states through precise separation measurements. The findings reveal a subtle balance in the joint formation, influencing the development of nanometer-sized structures at the contact zone and likely inducing built-in stresses in the interphase. This research illustrates how model materials can be tailored to control interactions between cellulose-rich surfaces, laying the groundwork for future high-resolution studies aimed at creating stiff, ductile, and/or tough joints between cellulose surfaces and to allow for the design of high-performance biobased materials.

Authorship equity in global health research: who gets the credit at University of California, San Francisco?

Authorship inequity exists in global health research and can be representative of unequal partnerships. Previous studies showed that low-income and middle-income country (LMIC) authors are under-represented in publications from global collaborative research between LMIC and high-income countries (HIC). However, there are little data on trends for how specific HIC institutions are performing concerning equitable authorship. We used Web of Science to find published articles affiliated with the University of California, San Francisco (UCSF), where an LMIC was referred to in the title, abstract or keywords from 2008 to 2021. The country affiliation of each author for all included articles was grouped based on World Bank data. A total of 5805 articles were included. On average, 53.6% (n=3109) of UCSF affiliated articles had at least one low-income country (LIC) or LMIC author; however, this number increased from 43.2% (n=63) in 2008 to 63.3% (n=421) in 2021. Overall, 16.3% (n=948) of UCSF affiliated articles had an LIC or LMIC researcher as the first author, 18.8% (n=1,059) had an LIC or LMIC researcher as second author, and 14.2% (n=820) had an LIC or LMIC researcher as last author. As long as manuscripts produced by UCSF have no LIC or LMIC authors included the university's commitment to authentic equity is undermined. Global health partnerships cannot be equitable without changing authorship trends between HIC and LMIC institutions.

Rapid and sustained contact tracing training for COVID-19 in San Francisco: a training model for developing an emergency public health workforce.

The City and County of San Francisco was the first municipality in the United States to institute a COVID-19 contact tracing program. The San Francisco Department of Public Health (SFDPH) and the University of California, San Francisco (UCSF) created an outcome-based fully remote contact tracing curriculum using participatory learning methods to train non-public health emergency workers as contact tracers. Between April and December 2020, we trained over 300 individuals in contact tracing skills and procedures over three training phases. Using iterative curriculum design and Kirkpatrick's evaluation methodology, we aimed to ensure high quality and successful person-centered contact tracing. The resulting curriculum consisted of 24 learning outcomes taught with six participatory skills development activities, asynchronous materials, and one-on-one contact tracer support. We collected more than 700 responses from trainees using various evaluation tools across the training phases, and contact tracers interviewed more than 24,000 contacts after training in our program. Our evaluations showed that knowledge and skills improved for most trainees and demonstrated the utility of the training program in preparing trainees to perform person-centered contact tracing in San Francisco. Local health jurisdictions and state health agencies can use this model of curriculum development and evaluation to rapidly train a non-public health workforce to respond to future public health emergencies.

Probabilistic cell seeding and non-autofluorescent 3D-printed structures as scalable approach for multi-level co-culture modeling.

To model complex biological tissue in vitro, a specific layout for the position and numbers of each cell type is necessary. Establishing such a layout requires manual cell placement in three dimensions (3D) with micrometric precision, which is complicated and time-consuming. Moreover, 3D printed materials used in compartmentalized microfluidic models are opaque or autofluorescent, hindering parallel optical readout and forcing serial characterization methods, such as patch-clamp probing. To address these limitations, we introduce a multi-level co-culture model realized using a parallel cell seeding strategy of human neurons and astrocytes on 3D structures printed with a commercially available non-autofluorescent resin at micrometer resolution. Using a two-step strategy based on probabilistic cell seeding, we demonstrate a human neuronal monoculture that forms networks on the 3D printed structure and can establish cell-projection contacts with an astrocytic-neuronal co-culture seeded on the glass substrate. The transparent and non-autofluorescent printed platform allows fluorescence-based immunocytochemistry and calcium imaging. This approach provides facile multi-level compartmentalization of different cell types and routes for pre-designed cell projection contacts, instrumental in studying complex tissue, such as the human brain.

Practitioner characteristics, diagnostic accuracy metrics and discovering-individual with respect to 637 melanomas documented by 27 general practitioners on the Skin Cancer Audit Research Database.

BACKGROUND AND OBJECTIVE: Knowledge of accuracy for melanoma diagnosis and melanoma discovering-individual in primary care is limited. We describe general practitioner (GP) characteristics and analyse defined diagnostic accuracy metrics for GPs in the current study comparing this with a previous study for GPs common to both, and we analyse the individual first discovering each melanoma as a lesion of concern. METHODS: The characteristics and diagnostic accuracy of 27 Australasian GPs documenting 637 melanomas on the Skin Cancer Audit Research Database (SCARD) in 2013 were described and analysed. The number needed to treat (NNT) and percentage of melanomas that were in situ (percentage in situ) were analysed as surrogates for specificity and sensitivity, respectively. The discovering-individual was analysed according to patient age and sex and lesion Breslow thickness. RESULTS: The average NNT and percentage in situ were 5.73% and 65.07%, respectively. For 21 GPs in both a 2008-2010 study and the current study, the NNT was 10.78 and 5.56, respectively (p = 0.0037). A consistent trend of decreasing NNT and increasing percentage in situ through increasingly subspecialised GP categories did not reach statistical significance. NNT trended high at ages and sites for which melanoma was rare. While the patient or family member was more likely to discover thick melanomas and melanomas in patients under 40 years, GPs discovered 73.9% of the melanomas as lesions of concern. CONCLUSIONS: GPs were the discovering-individuals for the majority of melanomas in the current study and their accuracy metrics compared favourably with published figures for dermatologists and GPs.

Processing strategy for reduced energy demand of nanostructured CNF/clay composites with tailored interfaces.

Nacre-mimicking nanocomposites based on colloidal cellulose nanofibrils (CNFs) and clay nanoparticles show excellent mechanical properties, yet processing typically involves preparation of two colloids followed by a mixing step, which is time- and energy-consuming. In this study, a facile preparation method using low energy kitchen blenders is reported in which CNF disintegration, clay exfoliation and mixing carried out in one step. Compared to composites made from the conventional method, the energy demand is reduced by about 97 %; the composites also show higher strength and work to fracture. Colloidal stability, CNF/clay nanostructure, and CNF/clay orientation are well characterized. The results suggest favorable effects from hemicellulose-rich, negatively charged pulp fibers and corresponding CNFs. CNF disintegration and colloidal stability are facilitated with substantial CNF/clay interfacial interaction. The results show a more sustainable and industrially relevant processing concept for strong CNF/clay nanocomposites.

SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice.

Inhibition of AMPK is tightly associated with metabolic perturbations upon over nutrition, yet the molecular mechanisms underlying are not clear. Here, we demonstrate the serine/threonine-protein phosphatase 6 regulatory subunit 3, SAPS3, is a negative regulator of AMPK. SAPS3 is induced under high fat diet (HFD) and recruits the PP6 catalytic subunit to deactivate phosphorylated-AMPK, thereby inhibiting AMPK-controlled metabolic pathways. Either whole-body or liver-specific deletion of SAPS3 protects male mice against HFD-induced detrimental consequences and reverses HFD-induced metabolic and transcriptional alterations while loss of SAPS3 has no effects on mice under balanced diets. Furthermore, genetic inhibition of AMPK is sufficient to block the protective phenotype in SAPS3 knockout mice under HFD. Together, our results reveal that SAPS3 is a negative regulator of AMPK and suppression of SAPS3 functions as a guardian when metabolism is perturbed and represents a potential therapeutic strategy to treat metabolic syndromes.