Acute glycemic and insulinemic effects of low-energy sweeteners: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: It has been suggested that low-energy sweeteners (LES) may be associated with an increased risk of metabolic diseases, possibly due to stimulation of glucose-responsive mechanisms. OBJECTIVE: We conducted a systematic review and meta-analysis of human intervention studies examining the acute effect of LES intake on postprandial glucose (PPG) and postprandial insulin (PPI) responses, in order to comprehensively and objectively quantify these relations. METHODS: We systematically searched the Medline, OVID FSTA, and SCOPUS databases until January 2020. Randomized controlled trials comparing acute postprandial effects on PPG and/or PPI after exposure to LES, either alone, with a meal, or with other nutrient-containing preloads to the same intervention without LES were eligible for inclusion. PPG and PPI responses were calculated as mean incremental area under the curve divided by time. Meta-analyses were performed using random effects models with inverse variance weighing. RESULTS: Twenty-six papers (34 PPG trials and 29 PPI trials) were included. There were no reports of statistically significant differences in the effects of LES on PPG and PPI responses compared with control interventions. Pooled effects of LES intake on the mean change difference in PPG and PPI were -0.02 mmol/L (95% CI: -0.09, 0.05) and -2.39 pmol/L (95% CI: -11.83, 7.05), respectively. The results did not appreciably differ by the type or dose of LES consumed, cointervention type, or fasting glucose and insulin levels. Among patients with type 2 diabetes, the mean change difference indicated a smaller PPG response after exposure to LES compared with the control (-0.3 mmol/L; 95% CI: -0.53, -0.07). CONCLUSIONS: Ingestion of LES, administered alone or in combination with a nutrient-containing preload, has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention. Apart from a small beneficial effect on PPG (-0.3 mmol/L) in studies enrolling patients with type 2 diabetes, the effects did not differ by type or dose of LES, or fasting glucose or insulin levels. This review and meta-analysis was registered at PROSPERO as CRD42018099608

Fiber Type Conversion by PGC-1α Activates Lysosomal and Autophagosomal Biogenesis in Both Unaffected and Pompe Skeletal Muscle

PGC-1α is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT) has only a partial effect in skeletal muscle. In our Pompe mouse model (KO), the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1α in muscle (tgKO). The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1α failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1α in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy

HIV testing strategies outside of health care settings in the European Union (EU)/European Economic Area (EEA): a systematic review to inform European Centre for Disease Prevention and Control guidance

Objectives: In recent years, new technologies and new approaches to scale up HIV testing have emerged. The objective of this paper was to synthesize the body of recent evidence on strategies aimed at increasing the uptake and coverage of HIV testing outside of health care settings in the European Union (EU)/European Economic Area (EEA). Methods: Systematic searches to identify studies describing effective HIV testing interventions and barriers to testing were run in five databases (2010–2017) with no language restrictions; the grey literature was searched for similar unpublished studies (2014–2017). Study selection, data extraction and critical appraisal were performed by two independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eighty studies on HIV testing in non-health care settings were identified, the majority set in Northern Europe. Testing was implemented in 65 studies, with men who have sex with men the risk group most often targeted. Testing coverage and positivity/reactivity rates varied widely by setting and population group. However, testing in community and outreach settings was effective at reaching people who had never previously been tested and acceptability of HIV testing, particularly rapid testing, outside of health care settings was found to be high. Other interventions aimed to increase HIV testing identified were: campaigns (n = 8), communication technologies (n = 2), education (n = 3) and community networking (n = 1). Conclusions: This review has identified several strategies with potential to achieve high HIV testing coverage outside of health care settings. However, the geographical spread of studies was limited, and few intervention studies reported before and after data, making it difficult to evaluate the impact of interventions on test coverage

Increased postprandial glycaemia, insulinemia, and lipidemia after 10 weeks’ sucrose-rich diet compared to an artificially sweetened diet: a randomised controlled trial

The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear. Objective: To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postprandial metabolic profiles after 10 weeks.Healthy overweight subjects were randomised to consume drinks and foods sweetened with either sucrose (∼2 g/kg body weight) (n = 12) or artificial sweeteners (n = 11) as supplements to their usual diet. Supplements were similar on the two diets and consisted of beverages (∼80 weight%) and solid foods (yoghurts, marmalade, ice cream, stewed fruits). The rest of the diet was free of choice and ad libitum. Before (week 0) and after the intervention (week 10) fasting blood samples were drawn and in week 10, postprandial blood was sampled during an 8-hour meal test (breakfast and lunch).After 10 weeks postprandial glucose, insulin, lactate, triglyceride, leptin, glucagon, and GLP-1 were all significantly higher in the sucrose compared with the sweetener group. After adjusting for differences in body weight changes and fasting values (week 10), postprandial glucose, lactate, insulin, GIP, and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake, postprandial lactate, insulin, GIP, and GLP-1 levels were still significantly higher on the sucrose-rich diet.A sucrose-rich diet consumed for 10 weeks resulted in significant elevations of postprandial glycaemia, insulinemia, and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects

Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

<p>Abstract</p> <p>Background</p> <p>Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies.</p> <p>Methods</p> <p>The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUV_max) were analyzed.</p> <p>Results</p> <p>The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUV_maxwas 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.</p> <p>Conclusions</p> <p>An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.</p

Increasing integrated testing in community settings through interventions for change, including the Spring European Testing Week

Background: Maximising access to testing by targeting more than one infection is effective in identifying new infections in settings or populations. Within the EU funded Joint Action INTEGRATE, this paper examined the feasibility and impact of expanding integrated testing for HIV, hepatitis C (HCV), chlamydia, gonorrhoea and/or syphilis in four community-based pilots through targeted interventions in Croatia, Italy and Poland and the Spring European Testing Week since community settings are key in detecting new infections and reaching key populations. Methods: Pilots led by local INTEGRATE partners prioritised testing for other infections or key populations. The Croatian pilot expanded testing for men who have sex with men to syphilis, chlamydia and gonorrhoea. Italian partners implemented a HIV and HCV testing/information event at a migrant centre. A second Italian pilot tested migrants for HIV and HCV through outreach and a low-threshold service for people who use drugs. Polish partners tested for HIV, HCV and syphilis among people who inject drugs in unstable housing via a mobile van. Pilots monitored the number of individuals tested for each infection and reactive results. The pilot Spring European Testing Week from 18 to 25 May 2018 was an INTEGRATE-driven initiative to create more testing awareness and opportunities throughout Europe. Results: The Croatian pilot found a high prevalence for each syphilis, chlamydia and gonorrhoea respectively, 2.1%, 12.4% and 6.7%. The Italian migrant centre pilot found low proportions who were previously tested for HIV (24%) or HCV (11%) and the second Italian pilot found an HCV prevalence of 6.2%, with low proportions previously tested for HIV (33%) or HCV (31%). The Polish pilot found rates of being previously tested for HIV, HCV and syphilis at 39%, 37%, and 38%, respectively. Results from the Spring European Testing Week pilot showed it was acceptable with increased integrated testing, from 50% in 2018 to 71% in 2019 in participants. Conclusions: Results show that integrated testing is feasible and effective in community settings, in reaching key populations and minimising missed testing opportunities, and the pilots made feasible because of the European collaboration and funding. For sustainability and expansion of integrated community testing across Europe, local government investment in legislation, financial and structural support are crucial.The INTEGRATE Joint Action was co-funded by the 3rd Health Programme of the European Union under grant agreement no 761319. The EuroTEST/European Testing Week initiative has received funding and grants from Gilead Sciences, ViiV Healthcare, Janssen, Merck/MSD and the European Commission under the 3rd and 2nd Health Programmes. HUHIV: CheckPoint Zagreb is funded by cooperation programs by the City of Zagreb and Ministry of Health incl. HIV, HCV and syphilis rapid tests, CT/NG tests are donated by Cepheid with the contribution of the Department of Immunological and Molecular Diagnostics of the Clinic for Infectious Diseases Dr Fran Mihaljević during the pilot project. CRI/FVM: For the pilot activity in the migrant centre, HIV and HCV rapid tests were donated by FVM/CRI. Moreover, FVM contributed with the staff and equipment (mobile unit). FVM: The medical centre and outreach street unit are funded by the Health Department of Lazio Regional Administration of Italy. NAC/FES: Funding for FES pilot in 2019 was provided by NAC. FES secured their staff, mobile unit and tests. Daniel Simões is the recipient of PhD Grant PD/BD/128008/2016 from Fundação para a Ciência e Tecnologia (FCT). All funders had no role in the study design, analysis, decision to publish, or preparation of the manuscript

Low-calorie sweeteners in the human diet: scientific evidence, recommendations, challenges and future needs. A symposium report from the FENS 2019 conference

Overconsumption of free sugars, particularly from sugar-sweetened beverages (SSB), has potential negative health impacts. Implementation of a range of public health strategies is needed to reduce intakes of free sugars, including reducing portion sizes, promoting healthier dietary choices and reformulating foods and beverages. Although low-calorie sweeteners (LCS) are a useful tool for reducing energy intake and control glucose response when consuming sweet foods and drinks, several opinions persist about the adverse health effects of LCS, many of which are based on poor, little or no scientific evidence. This symposium report summarises key messages of the presentations and related discussions delivered at a scientific symposium at the 13th European Nutrition Conference (FENS 2019). These presentations considered the scientific evidence and current recommendations about the use and potential benefits of LCS for human health, with a particular focus on current evidence in relation to body weight and glycaemic control. Many of the studies to date on LCS have focused on low-calorie sweetened beverages (LCSB); however, the psychological and behavioural factors influencing consumer beliefs and consumption of LCSB need to be further explored. Current recommendations for LCS use are described, including the conclusions from a recent expert consensus report identifying the challenges that remain with LCS research. Finally, existing knowledge gaps and future actions are described, as well as two large ongoing research projects: SWITCH and SWEET

A rapid non-iterative proper orthogonal decomposition based outlier detection and correction for PIV data

The present work proposes a novel method of detection and estimation of outliers in particle image velocimetry measurements by the modification of the temporal coefficients associated with a proper orthogonal decomposition of an experimental time series. Using synthetic outliers applied to two sequences of vector fields, the method is benchmarked against stateof-the-art approaches recently proposed to remove the influence of outliers. Compared with these methods, the proposed approach offers an increase in accuracy and robustness for the detection of outliers and comparable accuracy for their estimation