Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome.

Replacing sugar with non-nutritive artificial sweeteners (NAS) is a popular dietary choice for the prevention and management of metabolic syndrome and its comorbidities. However, evidence in human trials is conflicted regarding the efficacy of this strategy and whether NAS may counterintuitively promote, rather than prevent, metabolic derangements. The heterogeneity in outcomes may stem in part from microbiome variation between human participants and across research animal vivaria, leading to differential interactions of NAS with gut bacteria. An increasing body of evidence indicates that NAS can alter the mammalian gut microbiome composition, function, and metabolome, which can, in turn, influence host metabolic health. While there is evidence for microbiome-mediated metabolic shifts in response to NAS, the mechanisms by which NAS affect the gut microbiome, and how the microbiome subsequently affects host metabolic processes, remain unclear. In this viewpoint, we discuss data from human and animal trials and provide an overview of the current evidence for NAS-mediated microbial and metabolomic changes. We also review potential mechanisms through which NAS may influence the microbiome and delineate the next steps required to inform public health policies.

Predictive Factors for Conversion to Dementia in Individuals with Early-Onset Mild Cognitive Impairment.

INTRODUCTION: There is little research on factors predicting conversion to dementia in early-onset mild cognitive impairment (eoMCI), a transitional stage between healthy ageing and dementia in individuals below the age of 65. We aimed to examine whether sociodemographic and clinical factors at initial presentation predicted dementia progression in a cohort of eoMCI patients attending a memory service, at a university teaching hospital in the UK. METHODS: This is a retrospective case note study of individuals diagnosed with eoMCI between 2000 and 2013 at the Younger Person's Memory Service (YPMS) in Leicestershire, England. Data collected at assessment included social factors, demographic characteristics, and medical and psychiatric history, as well as standardized cognitive assessment scores. Variables were analysed using χ2 or independent sample t tests to identify associations. A Cox regression survival analysis was done to identify predictive factors for dementia conversion. An ROC analysis for total CAMCOG was used to investigate sensitivity and specificity for dementia converters versus non-converters. RESULTS: Out of 531 subjects who attended YPMS, 65 patients were given a diagnosis of eoMCI (47.7% female; mean age 56.4 ± 7.54 years). Of these, 21 (32.3%) converted to dementia during their course within the service. Comparison between subgroups revealed a significant association between dementia conversion and higher years of education and lower MMSE and CAMCOG (total and subscale) scores at baseline. Smoking history, alcohol use, or medical history such as diabetes or heart disease were not associated with conversion. Cox regression survival analysis showed higher education in years and lower total CAMCOG scores were significant predictors for conversion. Lower scores on the recent memory, remote memory, learning memory, and executive function subscales of the CAMCOG were also significant predictors for conversion. ROC curve analysis for total CAMCOG demonstrated that the best detection of dementia converters can be achieved with a cutoff score of 90.5/107 (sensitivity of 76.2% and specificity of 68.2%). Area under the curve was 0.808 (95% CI: 0.697-0.920). CONCLUSION: More years in education and lower cognitive scores on CAMCOG at initial assessment are associated with progression to dementia from eoMCI. Further research is required to explore these predictive factors more.

Ecology and Medicine Converge at the Microbiome-Host Interface.

The human body is home to a dense and diverse population of bacteria, viruses, and eukaryotes, collectively termed the microbiome. Research on host-microbiome interactions continuously demonstrates the importance of this microbial community to human physiology and its involvement in a myriad of diseases. This, in turn, sparks great interest in developing means for beneficially modulating the microbiome, such as fecal microbiome transplantation and probiotics. However, these interventions show mixed efficacy in clinical trials and raise safety concerns. How these exogenous microorganisms interact with the microbiome might underlie the efficacy and safety of these therapeutics, yet the signaling mechanisms mediating microbe-microbe interactions between human-dwelling commensals are poorly understood. In this commentary, we discuss known and putative mechanisms of interactions between commensals in the gut and how they can be harnessed for improving microbiome-targeting therapeutics and facilitating translation of microbiome research to the clinic.

A Review of Functional Neuroimaging in People with Down Syndrome with and without Dementia.

BACKGROUND: Individuals with Down syndrome (DS) are at high risk of dementia which is difficult to diagnose in DS. Neuroimaging has been identified as a potential tool to aid diagnosis by detecting changes in brain function. We carried out a review comparing functional neuroimaging in DS individuals with and without dementia. SUMMARY: A literature search was conducted using PubMed to identify relevant studies. In DS subjects with dementia, fluorodeoxyglucose-positron emission tomography (PET) studies showed glucose hypometabolism particularly in the parietal and/or temporal regions whilst magnetic resonance spectroscopy studies showed increased myoinositol and decreased N-acetylaspartate. Ligand-based PET studies revealed significant Pittsburgh compound B binding in DS subjects over the age of 40, particularly if they had dementia. KEY MESSAGES: Neuroimaging may aid the early detection of dementia in DS; however, further longitudinal studies are required.

The use or generation of biomedical data and existing medicines to discover and establish new treatments for patients with rare diseases - recommendations of the IRDiRC Data Mining and Repurposing Task Force.

The number of available therapies for rare diseases remains low, as fewer than 6% of rare diseases have an approved treatment option. The International Rare Diseases Research Consortium (IRDiRC) set up the multi-stakeholder Data Mining and Repurposing (DMR) Task Force to examine the potential of applying biomedical data mining strategies to identify new opportunities to use existing pharmaceutical compounds in new ways and to accelerate the pace of drug development for rare disease patients. In reviewing past successes of data mining for drug repurposing, and planning for future biomedical research capacity, the DMR Task Force identified four strategic infrastructure investment areas to focus on in order to accelerate rare disease research productivity and drug development: (1) improving the capture and sharing of self-reported patient data, (2) better integration of existing research data, (3) increasing experimental testing capacity, and (4) sharing of rare disease research and development expertise. Additionally, the DMR Task Force also recommended a number of strategies to increase data mining and repurposing opportunities for rare diseases research as well as the development of individualized and precision medicine strategies.

Can we reduce the number of MRSA screening site swabs in elective orthopedic patients?

BACKGROUND: Deep infection after routine elective orthopedic procedures can be catastrophic, leading to further surgery, loss of limb, disability, and risk of mortality. Ring-fencing elective orthopedic ward has been shown to significantly reduce the incidence of all postoperative infections especially with methicillin-resistant Staphylococcus aureus (MRSA). Our hospital's current MRSA screening is a four-site MRSA swabs. OBJECTIVES: This study evaluates the possibility of reducing the number of MRSA swab sites as part of a quality improvement project. STUDY DESIGN AND METHODS: Patients on the waiting list for elective orthopedic procedure in our trust who had an MRSA-positive swab from either four sites were analyzed over the time period from January 2012 to December 2014. Those without swabs from all four areas (nose, throat, axilla, and groin) were excluded. Positive swabs of different regions were recorded and compared. RESULTS: There were 138 MRSA-positive patients, giving an incidence of 31 per 10,000 screen/year over that time period. Some patients ( n = 31, 22.5%) had a positive swab in more than one site. The positive sites were as follows: nose (69.60%, n = 96), groin (26.10%, n = 36), throat (25.30%, n = 35), and axilla (8.70%, n = 12). In our cohort, we would miss a significant proportion of positive patients if we change it to a two swab screening policy (26.8% for nose and axilla combination; 18.10% for nose and groin combination; and 15.20% for nose and throat). However, we would only miss 2.2% of cases for a nose, groin, and throat three-swab policy. There were also 11 instances, where a previously negative site become positive in the next swab. CONCLUSION: A three-swab combination of nasal, throat, and groin swabs improves pickup rate of MRSA significantly compared to a two-swab policy and misses only 2.2% compared to a four-swab policy. Axilla swabbing does not make a significant difference to the results. Based on this study, the policy has now been changed from a four-swab to three-swab screening in our trust. This has now been audited four times and they were all negative. This has helped to reduce cost in terms of staff time and resources. We would not recommend screening only the previous positive site for the next repeat screening swabs as there is an 8% chance of missing MRSA carrier status.

Recommendations for the design of small population clinical trials.

BACKGROUND: Orphan drug development faces numerous challenges, including low disease prevalence, patient population heterogeneity, and strong presence of paediatric patient populations. Consequently, clinical trials for orphan drugs are often smaller than those of non-orphan drugs, and they require the development of efficient trial designs relevant to small populations to gain the most information from the available data. The International Rare Diseases Research Consortium (IRDiRC) is aimed at promoting international collaboration and advance rare diseases research worldwide, and has as one of its goals to contribute to 1000 new therapies for rare diseases. IRDiRC set up a Small Population Clinical Trials (SPCT) Task Force in order to address the shortcomings of our understanding in carrying out clinical trials in rare diseases. RESULTS: The IRDiRC SPCT Task Force met in March 2016 to discuss challenges faced in the design of small studies for rare diseases and present their recommendations, structured around six topics: different study methods/designs and their relation to different characteristics of medical conditions, adequate safety data, multi-arm trial designs, decision analytic approaches and rational approaches to adjusting levels of evidence, extrapolation, and patients' engagement in study design. CONCLUSIONS: Recommendations have been issued based on discussions of the Small Population Clinical Trials Task Force that aim to contribute towards successful therapy development and clinical use. While randomised clinical trials are still considered the gold standard, it is recommended to systematically take into consideration alternative trial design options when studying treatments for a rare disease. Combining different sources of safety data is important to give a fuller picture of a therapy's safety profile. Multi-arm trials should be considered an opportunity for rare diseases therapy development, and funders are encouraged to support such trial design via international networks. Patient engagement is critical in trial design and therapy development, a process which sponsors are encouraged to incorporate when conducting trials and clinical studies. Input from multiple regulatory agencies is recommended early and throughout clinical development. Regulators are often supportive of new clinical trial designs, provided they are well thought through and justified, and they also welcome discussions and questions on this topic. Parallel advice for multiregional development programs should also be considered.

The International Rare Diseases Research Consortium: Policies and Guidelines to maximize impact.

The International Rare Diseases Research Consortium (IRDiRC) has agreed on IRDiRC Policies and Guidelines, following extensive deliberations and discussions in 2012 and 2013, as a first step towards improving coordination of research efforts worldwide. The 25 funding members and 3 patient umbrella organizations (as of early 2013) of IRDiRC, a consortium of research funders that focuses on improving diagnosis and therapy for rare disease patients, agreed in Dublin, Ireland in April 2013 on the Policies and Guidelines that emphasize collaboration in rare disease research, the involvement of patients and their representatives in all relevant aspects of research, as well as the sharing of data and resources. The Policies and Guidelines provide guidance on ontologies, diagnostics, biomarkers, patient registries, biobanks, natural history, therapeutics, models, publication, intellectual property, and communication. Most IRDiRC members-currently nearly 50 strong-have since incorporated its policies in their funding calls and some have chosen to exceed the requirements laid out, for instance in relation to data sharing. The IRDiRC Policies and Guidelines are the first, detailed agreement of major public and private funding organizations worldwide to govern rare disease research, and may serve as a template for other areas of international research collaboration. While it is too early to assess their full impact on research productivity and patient benefit, the IRDiRC Policies and Guidelines have already contributed significantly to improving transparency and collaboration in rare disease research.

'IRDiRC Recognized Resources': a new mechanism to support scientists to conduct efficient, high-quality research for rare diseases.

The International Rare Diseases Research Consortium (IRDiRC) has created a quality label, 'IRDiRC Recognized Resources', formerly known as 'IRDiRC Recommended'. It is a peer-reviewed quality indicator process established based on the IRDiRC Policies and Guidelines to designate resources (ie, standards, guidelines, tools, and platforms) designed to accelerate the pace of discoveries and translation into clinical applications for the rare disease (RD) research community. In its first year of implementation, 13 resources successfully applied for this designation, each focused on key areas essential to IRDiRC objectives and to the field of RD research more broadly. These included data sharing for discovery, knowledge organisation and ontologies, networking patient registries, and therapeutic development. 'IRDiRC Recognized Resources' is a mechanism aimed to provide community-approved contributions to RD research higher visibility, and encourage researchers to adopt recognised standards, guidelines, tools, and platforms that facilitate research advances guided by the principles of interoperability and sharing.

Perceived body size affected by garment and body mass index.

This study investigated the effect of garment size on perceived body size. The perceived body sizes of nine Chinese men, with Body Mass Index between 17.0 and 37.1 kg/m(2), wearing five sizes of white T-shirts were assessed using Thompson and Gray's Nine-figural Scale. Garment sizes on perceived body sizes were different for those of different Body Mass Index. A backpropagation neural net model was used to model the nonlinear relationship between the perceived body size and the body's BMI, body chest girth, and garment ease (difference between garment and body chest girth). When the BMI was less than 20, wearing larger-sized T-shirts tended to increase perceived body size. For large chest sizes and for taller persons (BMI of 20 to 28) large garments made the wearer look thinner. However, for small persons (BMI of 20 to 28) effect of garment size was relatively small. Obese persons (BMI of > 28), wearing garments too tight or too loose were perceived as larger. Minimum perceived body size was found for garment ease of 2 to 3 cm.

Garment sizes in perception of body size.

This paper reports an experimental investigation of the effect of garment size on perceived body size. The perceived body sizes of three Chinese men (thin, medium, and obese build) wearing different sizes of white T-shirts were assessed using Thompson and Gray's 1995 Nine-figural Scale in 1 (thinnest) to 9 (obese) grade and a newly-proposed method. Within the limit of commercially available T-shirt sizes, for thin and medium persons, perceived body sizes are bigger when wearing T-shirts of larger sizes. For an obese person, however, wearing a large size T-shirt tends to make him look thinner. The study also showed that the newly proposed comparative method is more reliable in comparing body size perception but without measuring the magnitude of the change in body-size grade. The figural scale and the comparative method can be complementary.