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This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of topical treatments and skin‐resurfacing techniques for skin ageing that is sufficient for people to seek treatment, and to identify optimum treatment concentrations, frequencies of application and therapy durations.

Background While many studies have found an association between irritable bowel syndrome (IBS) and obesity, many others did not. Hence, this systematic review with meta-analysis aims to evaluate the relationship between obesity and IBS, and determine whether obesity correlates differently with the various IBS endotypes. Methods A systematic review of published literature was conducted in concordance with the PRISMA guidelines and followed by a meta-analysis of relevant studies using the random-effects model. The 34 included studies assessed obesity among non-IBS controls and IBS subjects, either as continuous or dichotomous outcomes, using body mass index (BMI) and waist circumference (WC). The standardized mean difference (SMD) and 95% confidence interval (CI); and the odds ratio (OR) and 95% CI were obtained for continuous and dichotomous outcomes respectively. Meta-regression was performed to identify sources of heterogeneity. Results We found a weak association between IBS and obesity, but this was not statistically significant. For BMI, the overall SMD was +0.227 (95% CI: –0.093 to 0.547, p = 0.164) and OR was 1.312 (95% CI: 0.974 to 1.767, p = 0.074). For WC, the overall SMD was +1.020 cm (95% CI: –1.768 to 3.807, p = 0.473). However, subgroup analysis revealed significantly higher BMI among IBS-diarrhoea (IBS-D) subjects compared to controls (SMD = +1.940; 95% CI: 0.679 to 3.200, p = 0.003) and significantly lower BMI among IBS-constipation (IBS-C) subjects compared to IBS-D subjects (SMD = –1.720; 95% CI: –2.489 to –0.950, p Conclusions In conclusion, our systematic review with meta-analysis showed that obesity is positively associated with diarrhoea-predominant IBS, but not IBS in general. Our findings support the exploration of shared pathophysiology between IBS-D and obesity.

Background We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian populations about the risks and benefits of data sharing are under-represented in prior attitudinal research. Methods We conducted seven focus groups with 62 participants in Singapore from May to July 2019. They were conducted in three languages (English, Mandarin and Malay) and analysed with qualitative content and thematic analysis. Results Four key themes emerged: nuanced understandings of data security and data sensitivity; trade-offs between data protection and research benefits; trust (and distrust) in the public and private sectors; and governance and control options. Participants were aware of the inherent risks associated with data sharing for research. Participants expressed conditional support for data sharing, including genomic sequence data and information contained within electronic medical records. This support included sharing data with researchers from universities and healthcare institutions, both in Singapore and overseas. Support was conditional on the perceived social value of the research and appropriate de-identification and data security processes. Participants suggested that a data sharing oversight body would help strengthen public trust and comfort in data research for PM in Singapore. Conclusion Maintenance of public trust in data security systems and governance regimes can enhance participation in PM and data sharing for research. Contrary to themes in much prior research, participants demonstrated a sophisticated understanding of the inherent risks of data sharing, analysed trade-offs between risks and potential benefits of PM, and often adopted an international perspective.

Context Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations. Objective To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals. Design and Participants We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants. Results Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P Conclusion We identified a deletion at SLC4A1 associated with HbA1c in Malay. The nonglycemic lowering of HbA1c at rs769664228 might cause individuals carrying this variant to be underdiagnosed for diabetes or prediabetes when HbA1c is used as the only diagnostic test for diabetes.

Metabolites are small intermediate products of cellular metabolism perturbed in a variety of complex disorders. Identifying genetic markers associated with metabolite concentrations could delineate disease-related metabolic pathways in humans. We tested genetic variants for associations with 136 metabolites in 1,954 Chinese from Singapore. At a conservative genome-wide threshold (3.7 x 10-10), we detected 1,899 variant-metabolite associations at 16 genetic loci. Three loci (ABCA7, A4GALT, GSTM2) represented novel associations with metabolites, with the strongest association observed between ABCA7 and d18:1/24:1 dihexosylceramide. Among 13 replicated loci, we identified six new variants independent of previously reported metabolite or lipid signals. We observed variant-metabolite associations at two loci (ABCA7, CHCHD2) that have been linked to neurodegenerative diseases. At SGPP1 and SPTLC3 loci, genetic variants showed preferential selectivity for sphingolipids with d16 (rather than d18) sphingosine backbone, including sphingosine-1-phosphate (S1P). Our results provide new genetic associations for metabolites and highlight the role of metabolites as intermediate modulators in disease metabolic pathways.

The plant virus, cowpea mosaic virus (CPMV), is increasingly being used as a nanoparticle platform for multivalent display of peptides. A growing variety of applications have employed the CPMV display technology including vaccines, antiviral therapeutics, nanoblock chemistry, and materials science. CPMV chimeras can be inexpensively produced from experimentally infected cowpea plants and are completely stable at 37 °C and low pH, suggesting that they could be used as edible or mucosally-delivered vaccines or therapeutics. However, the fate of CPMV particles in vivo, or following delivery via the oral route, is unknown. To address this question, we examined CPMV in vitro and in vivo. CPMV was shown to be stable under simulated gastric conditions in vitro. The pattern of localization of CPMV particles to mouse tissues following oral or intravenous dosing was then determined. For several days following oral or intravenous inoculation, CPMV was found in a wide variety of tissues throughout the body, including the spleen, kidney, liver, lung, stomach, small intestine, lymph nodes, brain, and bone marrow. CPMV particles were detected after cardiac perfusion, suggesting that the particles entered the tissues. This pattern was confirmed using methods to specifically detect the viral capsid proteins and the internal viral RNA. The stability of CPMV virions in the gastrointestinal tract followed by their systemic dissemination supports their use as orally bioavailable nanoparticles.

The plant virus cowpea mosaic virus (CPMV) has recently been developed as a biomolecular platform to display heterologous peptide sequences. Such CPMV-peptide chimeras can be easily and inexpensively produced in large quantities from experimentally infected plants. This study utilized the CPMV chimera platform to create an antiviral against measles virus (MV) by displaying a peptide known to inhibit MV infection. This peptide sequence corresponds to a portion of the MV binding site on the human MV receptor CD46. The CPMV-CD46 chimera efficiently inhibited MV infection of HeLa cells in vitro, while wild-type CPMV did not. Furthermore, CPMV-CD46 protected mice from mortality induced by an intracranial challenge with MV. Our results indicate that the inhibitory CD46 peptide expressed on the surface of CPMV retains virus-binding activity and is capable of inhibiting viral entry both in vitro and in vivo. The CD46 peptide presented in the context of CPMV is also up to 100-fold more effective than the soluble CD46 peptide at inhibiting MV infection in vitro. To our knowledge, this study represents the first utilization of a plant virus chimera as an antiviral agent.