No Changes in Human Immunodeficiency Virus (HIV) Suppression and Inflammatory Markers in Cerebrospinal Fluid in Patients Randomly Switched to Dolutegravir Plus Lamivudine (Spanish HIV/AIDS Research Network, PreEC/RIS 62)

A major concern of HIV dual therapy is a potential lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG+lamivudine (3TC). All participants maintained viral suppression in plasma and CSF at week 48. We observed no increase in CSF markers of inflammation or neuronal injury. Median (IQR) total and unbound DTG in CSF were 7.3(5.9-8.4) ng/mL and 1.7(1.2-1.9) ng/mL, respectively. DTG+3TC may maintain viral control without changes in inflammatory/injury markers within the CNS reservoir

Toxoplasma gondii IgG Serointensity Is Positively Associated With Frailty

Background: Persistent inflammation related to aging (inflammaging) is exacerbated by chronic infections and contributes to frailty in older adults. We hypothesized associations between Toxoplasma gondii (T. gondii), a common parasite causing an oligosymptomatic unremitting infection, and frailty, and secondarily between T. gondii and previously reported markers of immune activation in frailty.Methods: We analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) serointensity was measured with an enzyme-linked immunosorbent assay. The Fried criteria were used to define frailty status. Validated translations of Mini-Mental State Examination, Geriatric Depression Scale, and the Charlson Comorbidity Index were used to evaluate confounders. Previously analyzed biomarkers that were significantly associated with frailty in both prior reports and the current study, and also related to T. gondii serointensity, were further accounted for in multivariable logistic models with frailty as outcome.Results: In T. gondii-seropositives, there was a significant positive association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for multiple successive confounders. Among biomarkers linked with frailty, kynurenine/tryptophan and soluble tumor necrosis factor receptor II were positively associated with T. gondii serointensity in seropositives (p < .05). Associations with other biomarkers were not significant.Conclusions: This first reported association between T. gondii and frailty is limited by a cross-sectional design and warrants replication. While certain biomarkers of inflammaging were associated with both T. gondii IgG serointensity and frailty, they did not fully mediate the T. gondii-frailty association.This work was supported in part by the Spanish Ministry of Science and Innovation: MCIN/AEI/10.13039/501100011033(grant PID2020-113788RB-I00); Xunta de Galicia (grant ED431B 2022/16); Ministry of Education, Culture and Sport (grant BEAGAL18/00142 to V.V.); and Ministry of Economy and Competitiveness, cofinanced by the European Social Fund (grant RYC-2015-18394 to L.L.-L.). Additionally supported, in part, by the University of Maryland School of Medicine Center for Research on Aging in Baltimore, Maryland; a Clinical Science Research & Development Service Merit Award, Office of Research and Development, U.S. Department of Veterans Affairs, Washington, District of Columbia (grant 1 I01 CX001310-01 to T.T.P.); a R01 grant from the National Institute on Aging, National Institutes of Health, Bethesda, Maryland (grant NIA R01 AG018859 to E.J.K.); and by the Military and Veteran Microbiome: Consortium for Research and Education in Aurora, Colorado (L.A.B., A.J.H., C.A.L., T.T.P.). The opinions expressed in the article belong to the authors and cannot be construed as official positions or opinions of the funders, including the U.S. Veterans Affairs Administration and the National Institutes of Health. Data collected and used for the analyses reported in this article are not available because the initial consent did not include this sharing and because other primary analyses have not been completed. Funding for open access charge: Universidade da Coruna/CISUG

Simple large wood structures promote hydromorphological heterogeneity and benthic macroinvertebrate diversity in low-gradient rivers

This work has been carried out within the SMART Joint Doctorate Programme ‘Science for the MAnagement of Rivers and their Tidal systems’ funded by the Erasmus Mundus programme of the European Union

Functional Characterization of Circulating Tumor Cells with a Prostate-Cancer-Specific Microfluidic Device

Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs) from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that combines an anti-prostate specific membrane antigen (PSMA) antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45− cells) revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2–400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A) in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents