Artificially sweetened beverage consumption has steadily increased in the last 40 years. Several reviews examining the effects of artificially sweetened beverages on weight outcomes have ...discrepancies in their results and conclusions.
To determine whether risk of bias, results, and conclusions of reviews of effects of artificially sweetened beverage consumption on weight outcomes differ depending on review sponsorship and authors' financial conflicts of interest.
We performed a systematic review of reviews of the effects of artificially sweetened beverages on weight. Two assessors independently screened articles for inclusion, extracted data, and assessed risks of bias. We compared risk of bias, results and conclusions of reviews by different industry sponsors, authors' financial conflict of interest and journal sponsor. We also report the concordance between review results and conclusions.
Artificial sweetener industry sponsored reviews were more likely to have favorable results (3/4) than non-industry sponsored reviews (1/23), RR: 17.25 (95% CI: 2.34 to 127.29), as well as favorable conclusions (4/4 vs. 15/23), RR: 1.52 (95% CI: 1.14 to 2.06). All reviews funded by competitor industries reported unfavorable conclusions (4/4). In 42% of the reviews (13/31), authors' financial conflicts of interest were not disclosed. Reviews performed by authors that had a financial conflict of interest with the food industry (disclosed in the article or not) were more likely to have favorable conclusions (18/22) than reviews performed by authors without conflicts of interest (4/9), RR: 7.36 (95% CI: 1.15 to 47.22). Risk of bias was similar and high in most of the reviews.
Review sponsorship and authors' financial conflicts of interest introduced bias affecting the outcomes of reviews of artificially sweetened beverage effects on weight that could not be explained by other sources of bias.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In 1966, the National Institute of Dental Research (NIDR) began planning a targeted research program to identify interventions for widespread application to eradicate dental caries (tooth decay) ...within a decade. In 1971, the NIDR launched the National Caries Program (NCP). The objective of this paper is to explore the sugar industry's interaction with the NIDR to alter the research priorities of the NIDR NCP.
We used internal cane and beet sugar industry documents from 1959 to 1971 to analyze industry actions related to setting research priorities for the NCP. The sugar industry could not deny the role of sucrose in dental caries given the scientific evidence. They therefore adopted a strategy to deflect attention to public health interventions that would reduce the harms of sugar consumption rather than restricting intake. Industry tactics included the following: funding research in collaboration with allied food industries on enzymes to break up dental plaque and a vaccine against tooth decay with questionable potential for widespread application, cultivation of relationships with the NIDR leadership, consulting of members on an NIDR expert panel, and submission of a report to the NIDR that became the foundation of the first request for proposals issued for the NCP. Seventy-eight percent of the sugar industry submission was incorporated into the NIDR's call for research applications. Research that could have been harmful to sugar industry interests was omitted from priorities identified at the launch of the NCP. Limitations are that this analysis relies on one source of sugar industry documents and that we could not interview key actors.
The NCP was a missed opportunity to develop a scientific understanding of how to restrict sugar consumption to prevent tooth decay. A key factor was the alignment of research agendas between the NIDR and the sugar industry. This historical example illustrates how industry protects itself from potentially damaging research, which can inform policy makers today. Industry opposition to current policy proposals-including a World Health Organization guideline on sugars proposed in 2014 and changes to the nutrition facts panel on packaged food in the US proposed in 2014 by the US Food and Drug Administration-should be carefully scrutinized to ensure that industry interests do not supersede public health goals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In 1965, the Sugar Research Foundation (SRF) secretly funded a review in the New England Journal of Medicine that discounted evidence linking sucrose consumption to blood lipid levels and hence ...coronary heart disease (CHD). SRF subsequently funded animal research to evaluate sucrose's CHD risks. The objective of this study was to examine the planning, funding, and internal evaluation of an SRF-funded research project titled "Project 259: Dietary Carbohydrate and Blood Lipids in Germ-Free Rats," led by Dr. W.F.R. Pover at the University of Birmingham, Birmingham, United Kingdom, between 1967 and 1971. A narrative case study method was used to assess SRF Project 259 from 1967 to 1971 based on sugar industry internal documents. Project 259 found a statistically significant decrease in serum triglycerides in germ-free rats fed a high sugar diet compared to conventional rats fed a basic PRM diet (a pelleted diet containing cereal meals, soybean meals, whitefish meal, and dried yeast, fortified with a balanced vitamin supplement and trace element mixture). The results suggested to SRF that gut microbiota have a causal role in carbohydrate-induced hypertriglyceridemia. A study comparing conventional rats fed a high-sugar diet to those fed a high-starch diet suggested that sucrose consumption might be associated with elevated levels of beta-glucuronidase, an enzyme previously associated with bladder cancer in humans. SRF terminated Project 259 without publishing the results. The sugar industry did not disclose evidence of harm from animal studies that would have (1) strengthened the case that the CHD risk of sucrose is greater than starch and (2) caused sucrose to be scrutinized as a potential carcinogen. The influence of the gut microbiota in the differential effects of sucrose and starch on blood lipids, as well as the influence of carbohydrate quality on beta-glucuronidase and cancer activity, deserve further scrutiny.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The trafficking of components within cilia, called intraflagellar transport (IFT), is powered by kinesin-2 and dynein-2 motors. Loss of function in any subunit of the heterotrimeric KIF3A/KIF3B/KAP ...kinesin-2 motor prevents ciliogenesis in mammalian cells and has hindered an understanding of how kinesin-2 motors function in cilium assembly and IFT. We used a chemical-genetic approach to generate an inhibitable KIF3A/KIF3B/KAP kinesin-2 motor (i3A/i3B) that is capable of rescuing wild-type (WT) motor function for cilium assembly and Hedgehog signaling in Kif3a/Kif3b double-knockout cells. We demonstrate that KIF3A/KIF3B function is required not just for cilium assembly but also for cilium maintenance, as inhibition of i3A/i3B blocks IFT within 2 min and leads to a complete loss of primary cilia within 8 h. In contrast, inhibition of dynein-2 has no effect on cilium maintenance within the same time frame. The kinetics of cilia loss indicate that two processes contribute to ciliary disassembly in response to cessation of anterograde IFT: a slow shortening that is steady over time and a rapid deciliation that occurs with stochastic onset. We also demonstrate that the kinesin-2 family members KIF3A/KIF3C and KIF17 cannot rescue ciliogenesis in Kif3a/Kif3b double-knockout cells or delay the loss of assembled cilia upon i3A/i3B inhibition. These results demonstrate that KIF3A/KIF3B/KAP is the sole and essential motor for cilium assembly and maintenance in mammalian cells. These findings highlight differences in how kinesin-2 motors were adapted for cilium assembly and IFT function across species.
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•KIF3A/KIF3B/KAP is the sole intraflagellar transport motor in mammalian cells•Engineered, inhibitable KIF3A/KIF3B motors rescue wild-type motor function•Acute inhibition of KIF3A/KIF3B blocks anterograde IFT and leads to cilium loss•KIF3A/KIF3B/KAP is essential for ciliogenesis and cilium maintenance in mammals
Motors in the kinesin-2 family drive intraflagellar transport in cilia across species. Engelke et al. engineer a version of the heterotrimeric kinesin-2 motor KIF3A/KIF3B/KAP that can be acutely inhibited. They demonstrate that KIF3A/KIF3B/KAP is essential for the assembly and maintenance of primary cilia in Kif3a−/−;Kif3b−/− NIH 3T3 cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary The decline in hip fracture incidence is now accompanied by a further reduction in the likelihood of a recurrent hip fracture among survivors of the first fracture. Introduction Hip fracture ...incidence is declining in North America, but trends in hip fracture recurrence have not been described. Methods All hip fracture events among Olmsted County, Minnesota residents in 1980-2006 were identified. Secular trends were assessed using Poisson regression, and predictors of recurrence were evaluated with Andersen-Gill time-to-fracture regression models. Results Altogether, 2,752 hip fractures (median age, 83 years; 76% female) were observed, including 311 recurrences. Between 1980 and 2006, the incidence of a first-ever hip fracture declined by 1.37%/year for women (p < 0.001) and 0.06%/year for men (p = 0.917). Among 2,434 residents with a first-ever hip fracture, the cumulative incidence of a second hip fracture after 10 years was 11% in women and 6% in men with death treated as a competing risk. Age and calendar year of fracture were independently associated with hip fracture recurrence. Accounting for the reduction in first-ever hip fracture rates over time, hip fracture recurrence appeared to decline after 1997. Conclusion A recent reduction in hip fracture recurrence is somewhat greater than expected from the declining incidence of hip fractures generally. Additional research is needed to determine the extent to which this can be attributed to improved patient management.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A comprehensive study of the atmospheric neutrino flux in the energy region from sub-GeV up to several TeV using the Super-Kamiokande (SK) water Cherenkov detector is presented in this paper. The ...energy and azimuthal spectra, and variation over time, of the atmospheric νe+ν¯e and νμ+ν¯μ fluxes are measured. The energy spectra are obtained using an iterative unfolding method by combining various event topologies with differing energy responses. The azimuthal spectra depending on energy and zenith angle, and their modulation by geomagnetic effects, are also studied. A predicted east-west asymmetry is observed in both the νe and νμ samples at 8.0σ and 6.0σ significance, respectively, and an indication that the asymmetry dipole angle changes depending on the zenith angle was seen at the 2.2σ level. The measured energy and azimuthal spectra are consistent with the current flux models within the estimated systematic uncertainties. A study of the long-term correlation between the atmospheric neutrino flux and the solar magnetic activity cycle is performed, and a weak preference for a correlation was seen at the 1.1σ level, using SK-I–SK-IV data spanning a 20-year period. For several particularly strong solar activity periods, corresponding to Forbush decrease events, no theoretical prediction is available but a deviation below the typical neutrino event rate is seen at the 2.4σ level. The seasonal modulation of the neutrino flux is also examined, but the change in flux at the SK site is predicted to be negligible, and, as expected, no evidence for a seasonal correlation is seen.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Early warning signals of the coronary heart disease (CHD) risk of sugar (sucrose) emerged in the 1950s. We examined Sugar Research Foundation (SRF) internal documents, historical reports, and ...statements relevant to early debates about the dietary causes of CHD and assembled findings chronologically into a narrative case study. The SRF sponsored its first CHD research project in 1965, a literature review published in the New England Journal of Medicine, which singled out fat and cholesterol as the dietary causes of CHD and downplayed evidence that sucrose consumption was also a risk factor. The SRF set the review’s objective, contributed articles for inclusion, and received drafts. The SRF’s funding and role was not disclosed. Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD. Policymaking committees should consider giving less weight to food industry–funded studies and include mechanistic and animal studies as well as studies appraising the effect of added sugars on multiple CHD biomarkers and disease development.
Osteoporosis is a common condition that can be caused or exacerbated by estrogen deficiency.
This narrative review will discuss optimizing bone health in the setting of adjuvant endocrine treatments ...for hormone receptor-positive breast cancer and the current use of antiresorptive agents as adjuvant therapy and as bone modifying agents.
Adjuvant endocrine treatments for hormone receptor-positive breast cancer (tamoxifen and aromatase inhibitors) affect bone health. The exact effect depends on the agent used and the menopausal state of the woman. Antiresorptive medications for osteoporosis, bisphosphonates and denosumab, lower the risk of bone loss from aromatase inhibitors. Use of bisphosphonates as adjuvant treatment in breast cancer, regardless of hormone receptor status, is increasing because of benefits seen to cancer relapse and survival.
Optimizing bone health in women with breast cancer during and after cancer treatment is informed by an understanding of breast cancer treatment and its skeletal effect.
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