Sexually Segregated Housing Results in Improved Early larval Survival in Zebrafish

Large-scale aquaculture facilities require highly optimized husbandry protocols that maximize fecundity and embryo health while minimizing cost and effort. Although zebrafish are being increasingly used for preclinical drug screens, functional genomic research and toxicological and behavioral studies, many of the basic husbandry procedures that are used for these fish have not been thoroughly tested. In this study, the authors compared the breeding success of zebrafish housed in sex-separated and those housed in mixed-gender arrangements. They observed a significant increase in fecundity (egg production) between the first and the third breeding and found that egg survivorship tended to increase during successive pairings. The authors also found that zebrafish had higher fecundity, egg viability and seemed to have a higher breeding success rate when males and females were housed separately than when they were housed together

Candida bracarensis Detected among Isolates of Candida glabrata by Peptide Nucleic Acid Fluorescence In Situ Hybridization: Susceptibility Data and Documentation of Presumed Infection▿

Molecular taxonomic studies have revealed new Candida species among phenotypically delineated species, the best example being Candida dubliniensis. This study was designed to determine the occurrence of two new molecularly defined species, Candida bracarensis and Candida nivariensis, which are closely related to and identified as Candida glabrata by phenotypic assays. A total of 137 recent clinical isolates of C. glabrata identified by phenotypic characteristics was tested with C. bracarensis and C. nivariensis species-specific peptide nucleic acid fluorescence in situ hybridization probes. Three of 137 (2.2%) isolates were positive with the C. bracarensis probe, whereas the control strain, but none of the clinical isolates, was positive with the C. nivariensis probe. D1/D2 sequencing confirmed the identification of the three isolates as representing C. bracarensis. Clinically, one C. bracarensis isolate was recovered from a presumed infection, a polymicrobial pelvic abscess in a patient with perforated diverticulitis. The other two isolates were recovered from two adult oncology patients who were only colonized. C. bracarensis was white on CHROMagar Candida, had variable API-20C patterns that overlapped with C. nivariensis and some C. glabrata isolates, and had variable results with a rapid trehalose assay. Interestingly, an isolate from one of the colonized oncology patients was resistant to fluconazole, itraconazole, voriconazole, and posaconazole in vitro. In summary, C. bracarensis was detected among clinical isolates of C. glabrata, while C. nivariensis was not. One C. bracarensis isolate causing a presumed deep infection was recovered, and another isolate was azole resistant. Whether clinical laboratories should identify C. bracarensis will require more data

Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study

BACKGROUND: Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care.METHODS: We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales. Participants aged 18 or older referred with non-specific symptoms or symptoms potentially due to gynaecological, lung, or upper or lower gastrointestinal cancers were included and gave a blood sample when they attended for urgent investigation. Participants were excluded if they had a history of or had received treatment for an invasive or haematological malignancy diagnosed within the preceding 3 years, were taking cytotoxic or demethylating agents that might interfere with the test, or had participated in another study of a GRAIL MCED test. Patients were followed until diagnostic resolution or up to 9 months. Cell-free DNA was isolated and the MCED test performed blinded to the clinical outcome. MCED predictions were compared with the diagnosis obtained by standard care to establish the primary outcomes of overall positive and negative predictive value, sensitivity, and specificity. Outcomes were assessed in participants with a valid MCED test result and diagnostic resolution. SYMPLIFY is registered with ISRCTN (ISRCTN10226380) and has completed follow-up at all sites.FINDINGS: 6238 participants were recruited between July 7 and Nov 30, 2021, across 44 hospital sites. 387 were excluded due to staff being unable to draw blood, sample errors, participant withdrawal, or identification of ineligibility after enrolment. Of 5851 clinically evaluable participants, 376 had no MCED test result and 14 had no information as to final diagnosis, resulting in 5461 included in the final cohort for analysis with an evaluable MCED test result and diagnostic outcome (368 [6·7%] with a cancer diagnosis and 5093 [93·3%] without a cancer diagnosis). The median age of participants was 61·9 years (IQR 53·4-73·0), 3609 (66·1%) were female and 1852 (33·9%) were male. The MCED test detected a cancer signal in 323 cases, in whom 244 cancer was diagnosed, yielding a positive predictive value of 75·5% (95% CI 70·5-80·1), negative predictive value of 97·6% (97·1-98·0), sensitivity of 66·3% (61·2-71·1), and specificity of 98·4% (98·1-98·8). Sensitivity increased with increasing age and cancer stage, from 24·2% (95% CI 16·0-34·1) in stage I to 95·3% (88·5-98·7) in stage IV. For cases in which a cancer signal was detected among patients with cancer, the MCED test's prediction of the site of origin was accurate in 85·2% (95% CI 79·8-89·3) of cases. Sensitivity 80·4% (95% CI 66·1-90·6) and negative predictive value 99·1% (98·2-99·6) were highest for patients with symptoms mandating investigation for upper gastrointestinal cancer.INTERPRETATION: This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms.FUNDING: GRAIL Bio UK.</p

Sexually Segregated Housing Results in Improved Early larval Survival in Zebrafish

Large-scale aquaculture facilities require highly optimized husbandry protocols that maximize fecundity and embryo health while minimizing cost and effort. Although zebrafish are being increasingly used for preclinical drug screens, functional genomic research and toxicological and behavioral studies, many of the basic husbandry procedures that are used for these fish have not been thoroughly tested. In this study, the authors compared the breeding success of zebrafish housed in sex-separated and those housed in mixed-gender arrangements. They observed a significant increase in fecundity (egg production) between the first and the third breeding and found that egg survivorship tended to increase during successive pairings. The authors also found that zebrafish had higher fecundity, egg viability and seemed to have a higher breeding success rate when males and females were housed separately than when they were housed together