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ObjectivesTo determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA).MethodsA randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score.ResultsAlthough there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years.ConclusionsIn people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN 12607000415404).

Summary This study aimed to determine the effect of fish oil on bone mineral density (BMD). There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD. This randomized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on bone loss in adults. Introduction The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD. Methods In a multicentre, double-blind randomized controlled trial (RCT) (ACTRN 12607000415404), 202 Australian participants aged ≥40 with knee osteoarthritis (mean age, 61.0 ± 10.0 years; 49 % female) were randomized to receive either high dose (4.5 g eicosapentaenoic acid and docosahexaenoic acid daily) or low dose (0.45 g/day) omega-3 fish oil for 2 years. BMD was assessed at baseline and 2 years by dual energy X-ray absorptiometry. Results In subjects with baseline and 2-year assessments, mean standardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169 mg/cm 2 , respectively, for the lumbar spine and was 1035 ± 165 and 1017 ± 174 mg/cm 2 , respectively, for the femoral neck. There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses (lumbar spine 3.7, 95 % confidence interval (CI) −7.9 to 15.3 mg/cm 2 and femoral neck −5.5, 95 % CI −14.9 to 3.9 mg/cm 2 ). The findings did not change with additional adjustments of age, gender, study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants (≥55 years at the baseline) (all P  ≥ 0.25). Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group. There were no serious adverse events related to the intervention. Conclusion A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis.

Branched DNA (bDNA) is a signal amplification technology used in clinical and research laboratories to quantitatively detect nucleic acids. An overnight incubation is a significant drawback of highly sensitive bDNA assays. The VERSANT® HIV-1 RNA 3.0 Assay (bDNA) (\"Versant Assay\") currently used in clinical laboratories was modified to allow shorter target incubation, enabling the viral load assay to be run in a single day. To dramatically reduce the target incubation from 16-18 h to 2.5 h, composition of only the \"Lysis Diluent\" solution was modified. Nucleic acid probes in the assay were unchanged. Performance of the modified assay (assay in development; not commercially available) was evaluated and compared to the Versant Assay. Dilution series replicates (>950 results) were used to demonstrate that analytical sensitivity, linearity, accuracy, and precision for the shorter modified assay are comparable to the Versant Assay. HIV RNA-positive clinical specimens (n = 135) showed no significant difference in quantification between the modified assay and the Versant Assay. Equivalent relative quantification of samples of eight genotypes was demonstrated for the two assays. Elevated levels of several potentially interfering endogenous substances had no effect on quantification or specificity of the modified assay. The modified assay with drastically improved turnaround time demonstrates the viability of signal-amplifying technology, such as bDNA, as an alternative to the PCR-based assays dominating viral load monitoring in clinical laboratories. Highly sensitive bDNA assays with a single day turnaround may be ideal for laboratories with especially stringent cost, contamination, or reliability requirements.

Sir John Cornforth was a pioneer in discovering the detailed chemistry used by living systems to construct the organic substances they contain. From his teenage years, he was handicapped by profound deafness yet he overcame this to reach the highest pinnacles of scientific achievement. His work was carried out in several different research centres, both academic and medical, and he was a leading figure in all.

In part because humans cannot synthesize vitamin B 12 and must obtain it from organisms that produce it and because B 12 deficiency leads to pernicious anemia, it has been important to understand how microorganisms build this quite complex substance. As shown here, an interdisciplinary attack was needed, which combined the strengths of genetics, molecular biology, enzymology, chemistry, and spectroscopy. This allowed the step-by-step synthetic pathway of B 12 to be elucidated, and this approach has acted as a model for future research on the synthesis of substances in living organisms. One practical outcome of such an approach has been the improved availability of B 12 for animal feedstuffs and human health.

13C-labeled precorrin-6x is biosynthesized by cell-free protein preparations from Pseudomonas denitrificans in separate experiments using δ-amino[5-13C]levulinic acid and the corresponding δ-amino[4-13C]- and δ-amino[3-13C]levulinic acid-labeled forms in conjunction with S-[methyl-13C]adenosylmethionine for the latter two experiments. These labeled precorrin-6x samples, as their octamethyl esters, are studied by a range of NMR techniques. In addition, nuclear Overhauser effect difference measurements are made on unlabeled precorrin-6x ester to determine connectivities. The structure 6a so established for precorrin-6x ester (i) confirms the results reported in the preceding paper that precorrin-6x has a ring-contracted macrocycle, still carries the C-12 acetate residue, and stands at the oxidation level of a dehydrocorrin; (ii) reveals the unexpected methylation at C-11 not C-12, leading to a structure with separated chromophores; and (iii) implies that methyl migration from C-11 to C-12 occurs when precorrin-6x is converted into hydrogenobyrinic acid. Proposals for the biosynthesis of the corrin macrocycle of hydrogenobyrinic acid and vitamin B12are made.

Suicide is the leading cause of death among Australians. One commonly cited explanation is the impact of social media, in particular, the ways in which young people use social media to communicate about their own experiences and their exposure to suicide-related content posted by others. Guidelines designed to assist mainstream media to safely report about suicide are widespread. Until recently, no guidelines existed that targeted social media or young people. In response, we developed the #chatsafe guidelines and a supporting social media campaign, which together make up the #chatsafe intervention. The intervention was tested in a pilot study with positive results. However, the study was limited by the lack of a control group. The aim of this study is to assess the impact of the #chatsafe social media intervention on young people's safety and confidence when communicating on the web about suicide. The study employs a pragmatic, parallel, superiority randomized controlled design. It will be conducted in accordance with the Consolidated Standards of Reporting Trials statement over 18 months. Participants will be 400 young people aged 16-25 years (200 per arm). Participants will be recruited via social media advertising and assessed at 3 time points: time 1-baseline; time 2-8-week postintervention commencement; and time 3-4-week postintervention. They will be asked to complete a weekly survey to monitor safety and evaluate each piece of social media content. The intervention comprises an 8-week social media campaign including social media posts shared on public Instagram profiles. The intervention group will receive the #chatsafe suicide prevention content and the control group will receive sexual health content. Both groups will receive 24 pieces of content delivered to their mobile phones via text message. The primary outcome is safety when communicating on the web about suicide, as measured via the purpose-designed #chatsafe online safety questionnaire. Additional outcomes include willingness to intervene against suicide, internet self-efficacy, safety, and acceptability. The study was funded in November 2020, approved by the University of Melbourne Human Research Ethics Committee on October 7, 2022, and prospectively registered with the Australian New Zealand Clinical Trials registry. Trial recruitment began in November 2022 and study completion is anticipated by June 2024. This will be the first randomized controlled trial internationally to test the impact of a social media intervention designed to equip young people to communicate safely on the web about suicide. Given the rising rates of youth suicide in Australia and the acceptability of social media among young people, incorporating social media-based interventions into the suicide prevention landscape is an obvious next step. This intervention, if effective, could also be extended internationally, thereby improving web-based safety for young people not just in Australia but globally. Australian New Zealand Clinical Trials Registry ACTRN12622001397707; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384318. DERR1-10.2196/44300.

In part because humans cannot synthesize vitamin B12 and must obtain it from organisms that produce it and because B12 deficiency leads to pernicious anemia, it has been important to understand how microorganisms build this quite complex substance. As shown here, an interdisciplinary attack was needed, which combined the strengths of genetics, molecular biology, enzymology, chemistry, and spectroscopy. This allowed the step-by-step synthetic pathway of B12 to be elucidated, and this approach has acted as a model for future research on the synthesis of substances in living organisms. One practical outcome of such an approach has been the improved availability of B12 for animal feedstuffs and human health.