A genome–wide screen to identify genes controlling the rate of entry into mitosis in fission yeast

We have carried out a haploinsufficiency (HI) screen in fission yeast using heterozygous deletion diploid mutants of a genome-wide set of cell cycle genes to identify genes encoding products whose level determines the rate of progression through the cell cycle. Cell size at division was used as a measure of advancement or delay of the G2-M transition of rod-shaped fission yeast cells. We found that 13 mutants were significantly longer or shorter (greater than 10%) than control cells at cell division. These included mutants of the cdc2, cdc25, wee1 and pom1 genes, which have previously been shown to play a role in the timing of entry into mitosis, and which validate this approach. Seven of these genes are involved in regulation of the G2-M transition, 5 for nuclear transport and one for nucleotide metabolism. In addition we identified 4 more genes that were 8–10% longer or shorter than the control that also had roles in regulation of the G2-M transition or in nuclear transport. The genes identified here are all conserved in human cells, suggesting that this dataset will be useful as a basis for further studies to identify ratelimiting steps for progression through the cell cycle in other eukaryotes

Long-term Cross-reactivity Against Nonvaccine Human Papillomavirus Types 31 and 45 After 2- or 3-Dose Schedules of the AS04-Adjuvanted Human HPV-16/18 Vaccine

This analysis focused on long-term cross-reactive immunogenicity against nonvaccine human papillomavirus (HPV) types 31 and 45 following 2 doses of AS04-adjuvanted HPV-16/18 vaccine in girls aged 9-14 years or following 3 doses in women aged 15-25 years, for up to 3 years (HPV-070 study) and up to 5 years (HPV-048 study) after the first vaccination. Both schedules elicited antibodies against HPV-31 and HPV-45 up to 5 years after first dose. The antibody concentration was similar in young girls as compared to women. Specific CD4+ T-cell and B-cell responses to HPV-31 and HPV-45 at month 36 were similar across groups. Clinical trials registration: NCT01381575 and NCT00541970

Knowledge, attitude, and perception of Nigerian-based physiotherapists on the utilization of musculoskeletal ultrasound imaging in the clinical management of musculoskeletal conditions

Background: Musculoskeletal ultrasound imaging (MSUI) is an efficient monitoring and re-evaluation tool used for the management of musculoskeletal conditions in several clinical domains. Its utilization among physiotherapists, particularly in African countries, is yet to be explored. Objective: This study investigated the knowledge, attitude, and perception of physiotherapists on the utilization of MSUI in the clinical management of musculoskeletal conditions. Methods: One hundred and ninety-two consenting Nigerian-based physiotherapists practicing in public and private health institutions participated in this cross-sectional survey. They responded to a three-sectioned structured questionnaire, investigating socio-demographic and occupational characteristics, knowledge, attitude, and utilization of MSUI for the management of musculoskeletal conditions. Data were analyzed with descriptive statistics and Pearson’s chi-square test at a significant level of 0.05. Results: The majority (79.2%) of the respondents had positive knowledge of MSUI and its benefits as a clinical modality for managing MSCs. However, only 4.2% had utilized MSUI in clinical practice. Non-utilization of MSUI was commonly attributed to a lack of access to MSUI (60.3%) and its unavailability in most diagnostic centers (42.9%). Almost all (99.0%) of them agreed to the necessity for increased availability of MSUI to physiotherapists for enhancement of physiotherapy interventions in the management of MSCs. Conclusion: Knowledge of MSUI among Nigerian-based physiotherapists is adequate, but its utilization as a clinical tool is poor. Improved availability of MSUI to physiotherapists is necessary as well as specialty training on the utilization and interpretation of MSUI

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Synthesis of Imidazolin-2-iminato Titanium Complexes Containing Aryloxo Ligands and Their Catalytic Performance in the Polymerization of α‑Olefins

The synthesis of mixed (aryloxo)­(imidazolin-2-iminato)­titanium dichloride complexes is presented. Full characterization of the complexes, including solid-state X-ray diffraction analysis of four complexes, is reported. Their catalytic activity in the polymerization of ethylene, propylene, 1-hexene, and 1-octene was studied. The different substituents at the aryloxo moiety were found to have a substantial impact on the reactivity of the complexes, indicating the need for a balance of steric and electronic effects. The complex (1,3-di-<i>tert</i>-butylimidazolin-2-iminato)­(2,6-di-<i>tert-</i>butyl-4-methylphenoxide)­titanium dichloride (<b>1</b>) was found to be the most active in the polymerization of ethylene, whereas the complex (1,3-di-<i>tert</i>-butylimidazolin-2-iminato)­(2,6-di-<i>tert</i>-butylphenoxide)­titanium dichloride (<b>2</b>) was found to be the most active in the polymerization of propylene. Interestingly, all complexes were more active in the polymerization of propylene than in that of ethylene

Synthesis of Imidazolin-2-iminato Titanium Complexes Containing Aryloxo Ligands and Their Catalytic Performance in the Polymerization of α‑Olefins

The synthesis of mixed (aryloxo)­(imidazolin-2-iminato)­titanium dichloride complexes is presented. Full characterization of the complexes, including solid-state X-ray diffraction analysis of four complexes, is reported. Their catalytic activity in the polymerization of ethylene, propylene, 1-hexene, and 1-octene was studied. The different substituents at the aryloxo moiety were found to have a substantial impact on the reactivity of the complexes, indicating the need for a balance of steric and electronic effects. The complex (1,3-di-<i>tert</i>-butylimidazolin-2-iminato)­(2,6-di-<i>tert-</i>butyl-4-methylphenoxide)­titanium dichloride (<b>1</b>) was found to be the most active in the polymerization of ethylene, whereas the complex (1,3-di-<i>tert</i>-butylimidazolin-2-iminato)­(2,6-di-<i>tert</i>-butylphenoxide)­titanium dichloride (<b>2</b>) was found to be the most active in the polymerization of propylene. Interestingly, all complexes were more active in the polymerization of propylene than in that of ethylene

Synthesis of Imidazolin-2-iminato Titanium Complexes Containing Aryloxo Ligands and Their Catalytic Performance in the Polymerization of α‑Olefins

The synthesis of mixed (aryloxo)­(imidazolin-2-iminato)­titanium dichloride complexes is presented. Full characterization of the complexes, including solid-state X-ray diffraction analysis of four complexes, is reported. Their catalytic activity in the polymerization of ethylene, propylene, 1-hexene, and 1-octene was studied. The different substituents at the aryloxo moiety were found to have a substantial impact on the reactivity of the complexes, indicating the need for a balance of steric and electronic effects. The complex (1,3-di-<i>tert</i>-butylimidazolin-2-iminato)­(2,6-di-<i>tert-</i>butyl-4-methylphenoxide)­titanium dichloride (<b>1</b>) was found to be the most active in the polymerization of ethylene, whereas the complex (1,3-di-<i>tert</i>-butylimidazolin-2-iminato)­(2,6-di-<i>tert</i>-butylphenoxide)­titanium dichloride (<b>2</b>) was found to be the most active in the polymerization of propylene. Interestingly, all complexes were more active in the polymerization of propylene than in that of ethylene

Transmission and hybridisation dynamics of Schistosoma haematobium in the Senegal River Basin: No barrier breakdown between human and cattle schistosomiasis?

International audienc

Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease : A double-blind, randomized, placebo-controlled study

BACKGROUND: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. OBJECTIVE: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. METHODS: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. RESULTS: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs 3%, P = .04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P &lt; .001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. CONCLUSIONS: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism