We recently determined the crystal structure of the RNP domain of the U1 small nuclear ribonucleoprotein A and identified Arg and Lys residues involved in U1 RNA binding. These residues are clustered around the two highly conserved segments, RNP1 and RNP2, located in the central two beta strands. We have now studied the U1 RNA binding of mutants where potentially hydrogen bonding residues on the RNA binding surface were replaced by non‐hydrogen bonding residues. In the RNP2 segment, the Thr11‐‐‐‐Val and Asn15‐‐‐‐Val mutations completely abolished, and the Tyr13‐‐‐‐Phe and Asn16‐‐‐‐Val mutations substantially reduced the U1 RNA binding, suggesting that these residues form hydrogen bonds with the RNA. In the RNP1 segment Arg52‐‐‐‐Gln abolished, but Arg52‐‐‐‐Lys only slightly affected U1 RNA binding, suggesting that Arg52 may form a salt bridge with phosphates of U1 RNA. Ethylation protection experiments of U1 RNA show that the backbone phosphates of the 3′ two‐thirds of loop II and the 5′ stem are in contact with the U1 A protein. The U1 A protein‐U1 RNA binding constant is substantially reduced by A‐‐‐‐G and G‐‐‐‐A replacements in loop II, but not by C‐‐‐‐U or U‐‐‐‐C replacements. Based on these biochemical data we propose a structure for the complex between the U1 A ribonucleoprotein and U1 RNA.

Aim: To identify the barriers and facilitators to start insulin in patients with type 2 diabetes. Method: This was a systematic review. We conducted a systematic search using PubMed, EMBASE, CINAHL and Web of Science (up to 5 June 2014) for original English articles using the terms 'type 2 diabetes', 'insulin', and free texts: 'barrier' or 'facilitate' and 'initiate'. Two pairs of reviewers independently assessed and extracted the data. Study quality was assessed with Qualsyst. Results: A total of 9740 references were identified: 41 full-text articles were assessed for eligibility. Twenty-five articles (15 qualitative, 10 quantitative) were included in the review. Good inter-rater reliability was observed for the Qualsyst score (weighted kappa 0.7). Three main themes identified were as follows: patient-related, healthcare professional and system factors. The main patientrelated barriers were fear of pain and injection (n = 18), concerns about side effects of insulin (n = 12), perception that insulin indicated end stage of diabetes (n = 11), inconvenience (n = 10), difficulty in insulin administration (n = 7), punishment (n = 7) and stigma and discrimination (n = 7). Healthcare professionals' barriers were as follows: poor knowledge and skills (n = 9), physician inertia (n = 5) and language barriers (n = 4). System barriers included lack of time (n = 5). The most common facilitators were understanding the benefits of insulin (n = 7), not being afraid of injections (n = 5), and patient education and information (n = 5). Conclusion: Major barriers to insulin initiation persist despite availability of newer and safer insulin. Healthcare professionals should explore and address these barriers. Targeted interventions should be developed to overcome these barriers.

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Abstract:Rationale. Men have poorer health status and are less likely to attend health screening compared to women.Objective. This systematic review presents current evidence on the barriers and facilitators to engaging men in health screening.Methods. We included qualitative, quantitative and mixed-method studies identified through five electronic databases, contact with experts and reference mining. Two researchers selected and appraised the studies independently. Data extraction and synthesis were conducted using the 'best fit' framework synthesis method.Results. 53 qualitative, 44 quantitative and 6 mixed-method studies were included. Factors influencing health screening uptake in men can be categorized into five domains: individual, social, health system, healthcare professional and screening procedure. The most commonly reported barriers are fear of getting the disease and low risk perception; for facilitators, they are perceived risk and benefits of screening. Male-dominant barriers include heterosexualself-presentation, avoidance of femininity and lack of time. The partner's role is the most common male-dominant facilitator to screening.Conclusions. This systematic review provides a comprehensive overview of barriers and facilitators to health screening in men including the male-dominant factors. The findings are 3 particularly useful for clinicians, researchers and policy makers who are developing interventions and policies to increase screening uptake in men.4

BackgroundCancer incidence and mortality varies across region, sex and country’s economic status. While most studies focused on global trends, this study aimed to describe and analyse cancer incidence and mortality in Asia, focusing on cancer site, sex, region and income status.MethodsAge-standardised incidence and mortality rates of cancer were extracted from the GLOBOCAN 2012 database. Cancer mortality to incidence ratios (MIRs) were calculated to represent cancer survival. The data were analysed based on the four regions in Asia and income.ResultsCancer incidence rate is lower in Asia compared to the West but for MIR, it is the reverse. In Asia, the most common cancers in men are lung, stomach, liver, colorectal and oesophageal cancers while the most common cancers in women are breast, lung, cervical, colorectal and stomach cancers. The MIRs are the highest in lung, liver and stomach cancers and the lowest in colorectal, breast and prostate cancers. Eastern and Western Asia have a higher incidence of cancer compared to South-Eastern and South-Central Asia but this pattern is the reverse for MIR. Cancer incidence rate increases with country income particularly in colorectal and breast cancers but the pattern is the opposite for MIR.ConclusionThis study confirms that there is a wide variation in cancer incidence and mortality across Asia. This study is the first step towards documenting and explaining the changing cancer pattern in Asia in comparison to the rest of the world.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1615-0) contains supplementary material, which is available to authorized users.